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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2017-00436 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| S1612 | Other Identifier | SWOG | |
| S1612 | Other Identifier | CTEP | |
| U10CA180888 | U.S. NIH Grant/Contract | View source |
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This randomized phase II/III trial studies how well azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone work in treating older patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Drugs used in chemotherapy, such as azacitidine, decitabine, and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Midostaurin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving azacitidine with or without nivolumab or midostaurin, or decitabine and cytarabine alone may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To select, based on overall survival, any or all of the "Novel Therapeutic" regimens for further testing against azacitidine in patients age 60 and older with newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome with excessive blasts-2 (MDS-EB-2). (Phase II) II. To compare overall survival of the "Novel Therapeutic" regimens selected in the phase II portion of the trial to azacitidine in these patient populations. (Phase III)
SECONDARY OBJECTIVES:
I. To estimate the frequency and severity of toxicities of the regimens in these patient populations.
II. To estimate response rates, event-free survival, and relapse-free survival for these regimens in these patient populations.
TERTIARY OBJECTIVES:
I. To investigate associations between cytogenetic and molecular abnormalities (including FLT3) and outcomes for each of the regimens in these patient populations.
II. To bank specimens for future correlative studies.
OUTLINE: Patients are randomized to 1 of 4 arms.
ARM A: Patients receive azacitidine subcutaneously (SC) or intravenously (IV) daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM B: Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM C: Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM D:
INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for the 1st year, every 6 months for the 2nd and 3rd years, then annually until 5 years after randomization.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (azacitidine) | Active Comparator | Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
| Arm B (azacitidine, nivolumab) | Experimental | Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
| Arm C (azacitidine, midostaurin) | Experimental | Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
| Arm D (decitabine, cytarabine) | Experimental | INDUCTION: Patients receive decitabine IV over 2 hours on days 1-5 and cytarabine IV continuously on days 6-11. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients deemed stable at the discretion of the treating physician receive decitabine as in Induction. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Given SC or IV |
|
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) (Phase II) | Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died. | Day of registration on study until death from any cause, assessed for up to 5 years |
| OS (Phase III) | Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died. | Day of registration on study until death from any cause, assessed for up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Only adverse events that are possibly, probably, or definitely related to study drugs are reported. CTCAE Version 5.0 was used for all AE reporting. | Duration of treatment and follow up until death or 5 years post randomization (registration to Step 2). |
| Measure | Description | Time Frame |
|---|---|---|
| Remission Rates | #participants(ps) w comp response(resp)(CR), comp remission w incomp bld ct recovery(CRp/CRi), morphol leukemia-free state(MLFS), erythroid&neutrophil&platelet resp(HI-E,HI-N,HI-P), HI-P, marrow comp resp(CRm), stable disease(SD), no resp(NR) CR:BM blasts<5%; no circ blasts&blasts w Auer rods(AR); no extramedullary disease(ED); ANC≥1x10^9/L; plt ct≥100x10^9/L CRp/CRi:CR criteria excl residual neutropenia<1x10^9/L or ITP<100x10^9/L MLFS:BM blasts<5%; no blasts w AR, ED, hem recovery rqd HI-E:≥1.5g/dL↑Hb pretx;&RBC trans-depen ps, achieve trans independ or relevant↓RBC trans rqd HI-N:ANC↑pretx≥100%,&an absolute↑of>500/mm3 pretx HI-P:Absolute↑≥30000/mm3 pretx for ps w plt ct>20000/mm3 pretx. Ps w plt ct≤20000/mm3 pretx,↑≥100% pretx ct to plt ct>20000/mm3. Plt trans-depend ps, plt trans independ rqd CRm:CR for BM exam≤5%myeloblasts&marrow myeloblasts↓≥50%pretx SD:Not achieve≥PR, w no evidence prog NR:Not achieve CR,CRi,PR,MLFS,SD, excl ps w death in aplasia or due to indet cause |
Inclusion Criteria:
REGISTRATION STEP 1-SPECIMEN SUBMISSION
Patients must be suspected to have previously untreated acute myelogenous leukemia (AML) or myelodysplastic syndrome with excess blasts-2 (MDS-EB-2)
Patients must not be known to have AML in the central nervous system (CNS)
Patients must have specimens submitted for FLT3 testing for randomization stratification; collection of pretreatment specimens must be completed within 1 day of registration to Step 1; specimens must be submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System; FLT3 results will be used for stratification purposes at the time of randomization; E-mail notification of randomization assignment must be received prior to Step 2 registration
Patients must be offered participation in specimen banking; with patient consent, pretreatment specimens must be collected and submitted via the SWOG Specimen Tracking System
Patients who have received prior therapy with midostaurin, any anti-PD-1 or anti-PD-L1 therapy, any deoxyribonucleic acid (DNA)-methyltransferase inhibitor (including hypomethylating agents such as azacitidine, decitabine, or other investigational agent that acts by inhibiting DNA or ribonucleic acid [RNA] methylation) for any condition, or prior intensive cytotoxic therapy for myelodysplastic syndrome (MDS), are not eligible
Patients must be able to swallow oral medications without crushing or chewing
Prior malignancy is allowed providing it does not require concurrent therapy
Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception also includes (but is not limited to) heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or vasectomy; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system
REGISTRATION STEP 2-RANDOMIZATION: Patients must be registered to Step 2 no more than 42 days after registration to Step 1 and no more than 42 days after collection of specimens for FLT3 testing
REGISTRATION STEP 2-RANDOMIZATION: Patients must have morphologically confirmed, previously untreated acute myeloid leukemia (AML) or MDS with excess blasts-2 (MDS-EB-2)
REGISTRATION STEP 2-RANDOMIZATION: Patients must not be known to have AML in the CNS
REGISTRATION STEP 2-RANDOMIZATION: Patients must be deemed, in the judgment of the treating physician, to be ineligible for intensive induction therapy, or must have refused intensive induction therapy; rationale for clinical determination or notation of patient decision must be made
REGISTRATION STEP 2-RANDOMIZATION: Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 42 days prior to randomization (registration Step 2); reports of the results must be submitted
REGISTRATION STEP 2-RANDOMIZATION: FLT3 results will be used for stratification purposes at the time of randomization; E-mail notification that FLT3 specimens have been processed must be received prior to randomization (registration Step 2)
REGISTRATION STEP 2-RANDOMIZATION: Prior treatment with hydroxyurea is permitted; prior all-trans retinoic acid (ATRA) for suspected APL and prior intrathecal therapy are permitted, but must plan to be discontinued prior to initiating protocol therapy; patients with signs/symptoms of hyperleukocytosis or white blood cells (WBC) >= 50,000/mcL can be treated with leukapheresis prior to randomization (registration to Step 2)
REGISTRATION STEP 2-RANDOMIZATION: Patients may have received non-intensive therapy for antecedent hematologic disorders, including lenalidomide; patients may have received prior chemotherapy for prior cancers; these therapies must be discontinued at least 5 days prior to randomization (registration to Step 2)
REGISTRATION STEP 2-RANDOMIZATION: Patients who are transfusion-dependent and patients receiving growth factor support are eligible; patients must discontinue growth factor support prior to initiation of protocol therapy
REGISTRATION STEP 2-RANDOMIZATION: The following tests must be performed within 14 days prior to randomization (registration to Step 2) to establish baseline values:
REGISTRATION STEP 2-RANDOMIZATION: Patients must have complete history and physical examination within 28 days prior to randomization (registration to Step 2); history must include autoimmune disease status (to determine whether patient is eligible for Arm B)
REGISTRATION STEP 2-RANDOMIZATION: Patients must not have active infection (systemic bacterial, fungal, or viral infection) that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)
REGISTRATION STEP 2-RANDOMIZATION: Patients must be eligible for at least one of the currently active investigational treatment arms (S1612B or S1612C); if the patient does not meet eligibility criteria for at least one active investigational arm, then the patient is not eligible for S1612
REGISTRATION STEP 2-RANDOMIZATION: Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
ARM B (AZACITIDINE + NIVOLUMAB)
Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Patients must have AST and ALT =< 2.5 x institutional upper limit of normal (IULN)
Patients must have total bilirubin =< 1.5 x IULN
Patients must have baseline troponin test performed for eligibility; however, no associated values must be met in order for the patient to be eligible
ARM C (AZACITIDINE + MIDOSTAURIN)
Patients must have total bilirubin =< 2.5 x IULN
Patients must have creatinine clearance =< 2.5 x IULN
Patients must have corrected QT (QTc) interval < 500/msec (by Bazett's formula) on baseline ECG
Patients must not have any history of hypersensitivity to any drugs or metabolites of midostaurin
All tests for establishing baseline values must be completed within 14 days prior to registration to Step 2 (randomization)
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| Name | Affiliation | Role |
|---|---|---|
| Laura C Michaelis | SWOG Cancer Research Network | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Anchorage Associates in Radiation Medicine | Anchorage | Alaska | 98508 | United States | ||
| Alaska Breast Care and Surgery LLC |
78 participants were initially randomized to the study, 26 per arm. Two were ineligible, one on the Azacitidine+Nivolumab arm and one in the Azacitidine+Midostaurin arm. 76 participants were eligible and included in the primary analysis (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm).
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| ID | Title | Description |
|---|---|---|
| FG000 | Azacitidine | Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| FG001 | Azacitidine + Nivolumab |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 16, 2021 |
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| Cytarabine | Drug | Given IV |
|
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| Decitabine | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Midostaurin | Drug | Given PO |
|
|
| Nivolumab | Biological | Given IV |
|
|
| Up to 5 years |
| OS | Will be estimated using the Kaplan-Meier method or Cox regression models. Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed). | Day of registration on study until death from any cause, assessed for up to 5 years |
| Relapse-free Survival (RFS) | Time from the date of achievement of a remission (defined as patients achieving complete remission (CR), or CR with incomplete hematological recovery (CRi)) until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date of last contact. | Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years |
| Event-free Survival (EFS) | Time from from the date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause; patients not known to have any of these events are censored on the date of last contact. | Date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause, assessed for up to 5 years |
| Cumulative Incidence of Relapse Defined as Achieving CR or CRi | Cumulative incident endpoints and associations will be assessed using Cox regression models (for cause-specific hazards as appropriate). | Date of achievement of a remission until the date of relapse or death, assessed for up to 5 years |
| FLT3-ITD | The prognostic effect of FLT3-ITD (positive versus negative or non-evaluable) with respect to the outcome OS will be evaluated using Cox regression models. The predictive effect of FLT3-ITD (positive versus negative/non-evaluable) with respect to the outcome of OS and the treatments of azacitdine+midostaurin versus azacitidine will be evaluated using a Cox regression model with treatment arm and FLT3-ITD as covariates and including the interaction between the two covariates. | Up to 5 years |
| Cytogenetic Abnormalities, Risk Categories, and Mutations in Bone Marrow | Univariate and multivariable regression models will be used to assess potential associations between outcomes (CR, OS, EFS, and RFS) and cytogenetic abnormalities and mutation status (including FLT3-ITD). Regression models including interaction terms with treatment arm will be fit. In addition to analyzing FLT3-ITD as categorical variable used in randomization stratification, we will analyze FLT3-TKD also and evaluate FLT3-ITD allelic ratio as a quantitative variable and as a binary variable using the threshold of 0.50. | Up to 5 years |
| Potential Control Arm Drift | Only concurrently randomized patients will be evaluated in comparisons between arms. | Up to 5 years |
| Anchorage |
| Alaska |
| 99508 |
| United States |
| Alaska Oncology and Hematology LLC | Anchorage | Alaska | 99508 | United States |
| Alaska Women's Cancer Care | Anchorage | Alaska | 99508 | United States |
| Anchorage Oncology Centre | Anchorage | Alaska | 99508 | United States |
| Katmai Oncology Group | Anchorage | Alaska | 99508 | United States |
| Providence Alaska Medical Center | Anchorage | Alaska | 99508 | United States |
| University of Arizona Cancer Center-Orange Grove Campus | Tucson | Arizona | 85704 | United States |
| Banner University Medical Center - Tucson | Tucson | Arizona | 85719 | United States |
| University of Arizona Cancer Center-North Campus | Tucson | Arizona | 85719 | United States |
| CHI Saint Vincent Cancer Center Hot Springs | Hot Springs | Arkansas | 71913 | United States |
| John L McClellan Memorial Veterans Hospital | Little Rock | Arkansas | 72205 | United States |
| Kaiser Permanente-Deer Valley Medical Center | Antioch | California | 94531 | United States |
| Providence Saint Joseph Medical Center/Disney Family Cancer Center | Burbank | California | 91505 | United States |
| Kaiser Permanente-Fremont | Fremont | California | 94538 | United States |
| Fresno Cancer Center | Fresno | California | 93720 | United States |
| Kaiser Permanente-Fresno | Fresno | California | 93720 | United States |
| Fremont - Rideout Cancer Center | Marysville | California | 95901 | United States |
| Kaiser Permanente-Modesto | Modesto | California | 95356 | United States |
| Kaiser Permanente Oakland-Broadway | Oakland | California | 94611 | United States |
| Kaiser Permanente-Oakland | Oakland | California | 94611 | United States |
| Stanford Cancer Institute Palo Alto | Palo Alto | California | 94304 | United States |
| Kaiser Permanente-Rancho Cordova Cancer Center | Rancho Cordova | California | 95670 | United States |
| Kaiser Permanente-Redwood City | Redwood City | California | 94063 | United States |
| Kaiser Permanente-Richmond | Richmond | California | 94801 | United States |
| Rohnert Park Cancer Center | Rohnert Park | California | 94928 | United States |
| Kaiser Permanente-Roseville | Roseville | California | 95661 | United States |
| The Permanente Medical Group-Roseville Radiation Oncology | Roseville | California | 95678 | United States |
| Kaiser Permanente Downtown Commons | Sacramento | California | 95814 | United States |
| University of California Davis Comprehensive Cancer Center | Sacramento | California | 95817 | United States |
| Kaiser Permanente-South Sacramento | Sacramento | California | 95823 | United States |
| South Sacramento Cancer Center | Sacramento | California | 95823 | United States |
| Kaiser Permanente Sacramento Medical Center | Sacramento | California | 95825 | United States |
| Kaiser Permanente-San Francisco | San Francisco | California | 94115 | United States |
| Kaiser Permanente-Santa Teresa-San Jose | San Jose | California | 95119 | United States |
| Stanford Cancer Center South Bay | San Jose | California | 95124 | United States |
| Kaiser Permanente San Leandro | San Leandro | California | 94577 | United States |
| Kaiser Permanente-San Rafael | San Rafael | California | 94903 | United States |
| Kaiser San Rafael-Gallinas | San Rafael | California | 94903 | United States |
| Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | 95051 | United States |
| Kaiser Permanente-Santa Rosa | Santa Rosa | California | 95403 | United States |
| Kaiser Permanente Cancer Treatment Center | South San Francisco | California | 94080 | United States |
| Kaiser Permanente-South San Francisco | South San Francisco | California | 94080 | United States |
| Kaiser Permanente-Stockton | Stockton | California | 95210 | United States |
| Gene Upshaw Memorial Tahoe Forest Cancer Center | Truckee | California | 96161 | United States |
| Kaiser Permanente Medical Center-Vacaville | Vacaville | California | 95688 | United States |
| Kaiser Permanente-Vallejo | Vallejo | California | 94589 | United States |
| Kaiser Permanente-Walnut Creek | Walnut Creek | California | 94596 | United States |
| Rocky Mountain Cancer Centers-Aurora | Aurora | Colorado | 80012 | United States |
| Boulder Community Hospital | Boulder | Colorado | 80301 | United States |
| Rocky Mountain Cancer Centers-Boulder | Boulder | Colorado | 80304 | United States |
| Penrose-Saint Francis Healthcare | Colorado Springs | Colorado | 80907 | United States |
| Rocky Mountain Cancer Centers-Penrose | Colorado Springs | Colorado | 80907 | United States |
| Denver Health Medical Center | Denver | Colorado | 80204 | United States |
| Kaiser Permanente-Franklin | Denver | Colorado | 80205 | United States |
| National Jewish Health-Main Campus | Denver | Colorado | 80206 | United States |
| The Women's Imaging Center | Denver | Colorado | 80209 | United States |
| Porter Adventist Hospital | Denver | Colorado | 80210 | United States |
| Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States |
| Presbyterian - Saint Lukes Medical Center - Health One | Denver | Colorado | 80218 | United States |
| Rocky Mountain Cancer Centers-Midtown | Denver | Colorado | 80218 | United States |
| Saint Joseph Hospital - Cancer Centers of Colorado | Denver | Colorado | 80218 | United States |
| Rocky Mountain Cancer Centers-Rose | Denver | Colorado | 80220 | United States |
| Western Surgical Care | Denver | Colorado | 80220 | United States |
| Mercy Medical Center | Durango | Colorado | 81301 | United States |
| Southwest Oncology PC | Durango | Colorado | 81301 | United States |
| Mountain Blue Cancer Care Center - Swedish | Englewood | Colorado | 80113 | United States |
| Swedish Medical Center | Englewood | Colorado | 80113 | United States |
| Poudre Valley Hospital | Fort Collins | Colorado | 80524 | United States |
| Mountain Blue Cancer Care Center | Golden | Colorado | 80401 | United States |
| National Jewish Health-Western Hematology Oncology | Golden | Colorado | 80401 | United States |
| Saint Mary's Hospital and Regional Medical Center | Grand Junction | Colorado | 81501 | United States |
| Banner North Colorado Medical Center | Greeley | Colorado | 80631 | United States |
| Good Samaritan Hospital - Cancer Centers of Colorado | Lafayette | Colorado | 80026 | United States |
| Kaiser Permanente-Rock Creek | Lafayette | Colorado | 80026 | United States |
| Rocky Mountain Cancer Centers-Lakewood | Lakewood | Colorado | 80228 | United States |
| Saint Anthony Hospital | Lakewood | Colorado | 80228 | United States |
| Rocky Mountain Cancer Centers-Littleton | Littleton | Colorado | 80120 | United States |
| Littleton Adventist Hospital | Littleton | Colorado | 80122 | United States |
| Kaiser Permanente-Lone Tree | Lone Tree | Colorado | 80124 | United States |
| Rocky Mountain Cancer Centers-Sky Ridge | Lone Tree | Colorado | 80124 | United States |
| Longmont United Hospital | Longmont | Colorado | 80501 | United States |
| Rocky Mountain Cancer Centers-Longmont | Longmont | Colorado | 80501 | United States |
| Banner McKee Medical Center | Loveland | Colorado | 80539 | United States |
| Parker Adventist Hospital | Parker | Colorado | 80138 | United States |
| Rocky Mountain Cancer Centers-Parker | Parker | Colorado | 80138 | United States |
| Saint Mary Corwin Medical Center | Pueblo | Colorado | 81004 | United States |
| Rocky Mountain Cancer Centers - Pueblo | Pueblo | Colorado | 81008 | United States |
| National Jewish Health-Northern Hematology Oncology | Thornton | Colorado | 80260 | United States |
| Rocky Mountain Cancer Centers-Thornton | Thornton | Colorado | 80260 | United States |
| Intermountain Health Lutheran Hospital | Wheat Ridge | Colorado | 80401 | United States |
| Beebe Medical Center | Lewes | Delaware | 19958 | United States |
| Delaware Clinical and Laboratory Physicians PA | Newark | Delaware | 19713 | United States |
| Helen F Graham Cancer Center | Newark | Delaware | 19713 | United States |
| Medical Oncology Hematology Consultants PA | Newark | Delaware | 19713 | United States |
| Christiana Care Health System-Christiana Hospital | Newark | Delaware | 19718 | United States |
| Beebe Health Campus | Rehoboth Beach | Delaware | 19971 | United States |
| TidalHealth Nanticoke / Allen Cancer Center | Seaford | Delaware | 19973 | United States |
| Christiana Care Health System-Wilmington Hospital | Wilmington | Delaware | 19801 | United States |
| Mayo Clinic in Florida | Jacksonville | Florida | 32224-9980 | United States |
| The Watson Clinic | Lakeland | Florida | 33805 | United States |
| Sacred Heart Hospital | Pensacola | Florida | 32504 | United States |
| Moffitt Cancer Center | Tampa | Florida | 33612 | United States |
| John B Amos Cancer Center | Columbus | Georgia | 31904 | United States |
| Kaiser Permanente Moanalua Medical Center | Honolulu | Hawaii | 96819 | United States |
| Saint Alphonsus Cancer Care Center-Boise | Boise | Idaho | 83706 | United States |
| Saint Luke's Cancer Institute - Boise | Boise | Idaho | 83712 | United States |
| Saint Alphonsus Cancer Care Center-Caldwell | Caldwell | Idaho | 83605 | United States |
| Kootenai Health - Coeur d'Alene | Coeur d'Alene | Idaho | 83814 | United States |
| Walter Knox Memorial Hospital | Emmett | Idaho | 83617 | United States |
| Saint Luke's Cancer Institute - Fruitland | Fruitland | Idaho | 83619 | United States |
| Idaho Urologic Institute-Meridian | Meridian | Idaho | 83642 | United States |
| Saint Luke's Cancer Institute - Meridian | Meridian | Idaho | 83642 | United States |
| Saint Alphonsus Cancer Care Center-Nampa | Nampa | Idaho | 83687 | United States |
| Saint Luke's Cancer Institute - Nampa | Nampa | Idaho | 83687 | United States |
| Kootenai Clinic Cancer Services - Post Falls | Post Falls | Idaho | 83854 | United States |
| Kootenai Clinic Cancer Services - Sandpoint | Sandpoint | Idaho | 83864 | United States |
| Saint Luke's Cancer Institute - Twin Falls | Twin Falls | Idaho | 83301 | United States |
| Rush - Copley Medical Center | Aurora | Illinois | 60504 | United States |
| Illinois CancerCare-Bloomington | Bloomington | Illinois | 61704 | United States |
| Illinois CancerCare-Canton | Canton | Illinois | 61520 | United States |
| Memorial Hospital of Carbondale | Carbondale | Illinois | 62902 | United States |
| SIH Cancer Institute | Carterville | Illinois | 62918 | United States |
| Illinois CancerCare-Carthage | Carthage | Illinois | 62321 | United States |
| Centralia Oncology Clinic | Centralia | Illinois | 62801 | United States |
| Carle at The Riverfront | Danville | Illinois | 61832 | United States |
| Cancer Care Specialists of Illinois - Decatur | Decatur | Illinois | 62526 | United States |
| Decatur Memorial Hospital | Decatur | Illinois | 62526 | United States |
| Carle Physician Group-Effingham | Effingham | Illinois | 62401 | United States |
| Crossroads Cancer Center | Effingham | Illinois | 62401 | United States |
| Illinois CancerCare-Eureka | Eureka | Illinois | 61530 | United States |
| Illinois CancerCare-Galesburg | Galesburg | Illinois | 61401 | United States |
| Western Illinois Cancer Treatment Center | Galesburg | Illinois | 61401 | United States |
| Ingalls Memorial Hospital | Harvey | Illinois | 60426 | United States |
| Edward Hines Jr VA Hospital | Hines | Illinois | 60141 | United States |
| Illinois CancerCare-Kewanee Clinic | Kewanee | Illinois | 61443 | United States |
| Illinois CancerCare-Macomb | Macomb | Illinois | 61455 | United States |
| Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois | 61938 | United States |
| Loyola University Medical Center | Maywood | Illinois | 60153 | United States |
| Marjorie Weinberg Cancer Center at Loyola-Gottlieb | Melrose Park | Illinois | 60160 | United States |
| Good Samaritan Regional Health Center | Mount Vernon | Illinois | 62864 | United States |
| Cancer Care Center of O'Fallon | O'Fallon | Illinois | 62269 | United States |
| Illinois CancerCare-Ottawa Clinic | Ottawa | Illinois | 61350 | United States |
| Illinois CancerCare-Pekin | Pekin | Illinois | 61554 | United States |
| OSF Saint Francis Radiation Oncology at Pekin | Pekin | Illinois | 61554 | United States |
| Illinois CancerCare-Peoria | Peoria | Illinois | 61615 | United States |
| OSF Saint Francis Radiation Oncology at Peoria Cancer Center | Peoria | Illinois | 61615 | United States |
| Methodist Medical Center of Illinois | Peoria | Illinois | 61636 | United States |
| OSF Saint Francis Medical Center | Peoria | Illinois | 61637 | United States |
| Illinois CancerCare-Peru | Peru | Illinois | 61354 | United States |
| Valley Radiation Oncology | Peru | Illinois | 61354 | United States |
| Illinois CancerCare-Princeton | Princeton | Illinois | 61356 | United States |
| UW Health Carbone Cancer Center Rockford | Rockford | Illinois | 61114 | United States |
| Southern Illinois University School of Medicine | Springfield | Illinois | 62702 | United States |
| Springfield Clinic | Springfield | Illinois | 62702 | United States |
| Springfield Memorial Hospital | Springfield | Illinois | 62781 | United States |
| Southwest Illinois Health Services LLP | Swansea | Illinois | 62226 | United States |
| Carle Cancer Center | Urbana | Illinois | 61801 | United States |
| The Carle Foundation Hospital | Urbana | Illinois | 61801 | United States |
| Rush-Copley Healthcare Center | Yorkville | Illinois | 60560 | United States |
| Parkview Hospital Randallia | Fort Wayne | Indiana | 46805 | United States |
| Parkview Regional Medical Center | Fort Wayne | Indiana | 46845 | United States |
| Indiana University/Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Sidney and Lois Eskenazi Hospital | Indianapolis | Indiana | 46202 | United States |
| Reid Health | Richmond | Indiana | 47374 | United States |
| Mary Greeley Medical Center | Ames | Iowa | 50010 | United States |
| McFarland Clinic - Ames | Ames | Iowa | 50010 | United States |
| McFarland Clinic - Boone | Boone | Iowa | 50036 | United States |
| Mercy Cancer Center-West Lakes | Clive | Iowa | 50325 | United States |
| Mission Cancer and Blood - West Des Moines | Clive | Iowa | 50325 | United States |
| Alegent Health Mercy Hospital | Council Bluffs | Iowa | 51503 | United States |
| Greater Regional Medical Center | Creston | Iowa | 50801 | United States |
| Iowa Methodist Medical Center | Des Moines | Iowa | 50309 | United States |
| Mission Cancer and Blood - Des Moines | Des Moines | Iowa | 50309 | United States |
| Broadlawns Medical Center | Des Moines | Iowa | 50314 | United States |
| Mercy Medical Center - Des Moines | Des Moines | Iowa | 50314 | United States |
| Mission Cancer and Blood - Laurel | Des Moines | Iowa | 50314 | United States |
| Iowa Lutheran Hospital | Des Moines | Iowa | 50316 | United States |
| McFarland Clinic - Trinity Cancer Center | Fort Dodge | Iowa | 50501 | United States |
| Trinity Regional Medical Center | Fort Dodge | Iowa | 50501 | United States |
| McFarland Clinic - Jefferson | Jefferson | Iowa | 50129 | United States |
| McFarland Clinic - Marshalltown | Marshalltown | Iowa | 50158 | United States |
| Methodist West Hospital | West Des Moines | Iowa | 50266-7700 | United States |
| Mercy Medical Center-West Lakes | West Des Moines | Iowa | 50266 | United States |
| Central Care Cancer Center - Garden City | Garden City | Kansas | 67846 | United States |
| Central Care Cancer Center - Great Bend | Great Bend | Kansas | 67530 | United States |
| Lawrence Memorial Hospital | Lawrence | Kansas | 66044 | United States |
| Kansas Institute of Medicine Cancer and Blood Center | Lenexa | Kansas | 66219 | United States |
| Minimally Invasive Surgery Hospital | Lenexa | Kansas | 66219 | United States |
| Menorah Medical Center | Overland Park | Kansas | 66209 | United States |
| Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita | Kansas | 67208 | United States |
| Ascension Via Christi Hospitals Wichita | Wichita | Kansas | 67214 | United States |
| Cancer Center of Kansas - Wichita | Wichita | Kansas | 67214 | United States |
| Wesley Medical Center | Wichita | Kansas | 67214 | United States |
| Flaget Memorial Hospital | Bardstown | Kentucky | 40004 | United States |
| Commonwealth Cancer Center-Corbin | Corbin | Kentucky | 40701 | United States |
| Saint Joseph Radiation Oncology Resource Center | Lexington | Kentucky | 40504 | United States |
| Saint Joseph Hospital East | Lexington | Kentucky | 40509 | United States |
| Saint Joseph London | London | Kentucky | 40741 | United States |
| Jewish Hospital | Louisville | Kentucky | 40202 | United States |
| Saints Mary and Elizabeth Hospital | Louisville | Kentucky | 40215 | United States |
| UofL Health Medical Center Northeast | Louisville | Kentucky | 40245 | United States |
| Jewish Hospital Medical Center South | Shepherdsville | Kentucky | 40165 | United States |
| Ochsner Health Center-Summa | Baton Rouge | Louisiana | 70809 | United States |
| Medical Center of Baton Rouge | Baton Rouge | Louisiana | 70816 | United States |
| Ochsner Medical Center Jefferson | New Orleans | Louisiana | 70121 | United States |
| Harold Alfond Center for Cancer Care | Augusta | Maine | 04330 | United States |
| Eastern Maine Medical Center | Bangor | Maine | 04401 | United States |
| Waldo County General Hospital | Belfast | Maine | 04915 | United States |
| MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford | Biddeford | Maine | 04005 | United States |
| Lafayette Family Cancer Center-EMMC | Brewer | Maine | 04412 | United States |
| Penobscot Bay Medical Center | Rockport | Maine | 04856 | United States |
| MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford | Sanford | Maine | 04073 | United States |
| Mercy Medical Center | Springfield | Massachusetts | 01104 | United States |
| Baystate Medical Center | Springfield | Massachusetts | 01199 | United States |
| Trinity Health Saint Joseph Mercy Hospital Ann Arbor | Ann Arbor | Michigan | 48106 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Brighton | Brighton | Michigan | 48114 | United States |
| Trinity Health Medical Center - Brighton | Brighton | Michigan | 48114 | United States |
| Henry Ford Cancer Institute-Downriver | Brownstown | Michigan | 48183 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Canton | Canton | Michigan | 48188 | United States |
| Trinity Health Medical Center - Canton | Canton | Michigan | 48188 | United States |
| Caro Cancer Center | Caro | Michigan | 48723 | United States |
| Chelsea Hospital | Chelsea | Michigan | 48118 | United States |
| Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Chelsea | Michigan | 48118 | United States |
| Hematology Oncology Consultants-Clarkston | Clarkston | Michigan | 48346 | United States |
| Newland Medical Associates-Clarkston | Clarkston | Michigan | 48346 | United States |
| Henry Ford Macomb Hospital-Clinton Township | Clinton Township | Michigan | 48038 | United States |
| Henry Ford Medical Center-Fairlane | Dearborn | Michigan | 48126 | United States |
| Wayne State University/Karmanos Cancer Institute | Detroit | Michigan | 48201 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Henry Ford Health Saint John Hospital | Detroit | Michigan | 48236 | United States |
| Henry Ford River District Hospital | East China Township | Michigan | 48054 | United States |
| OSF Saint Francis Hospital and Medical Group | Escanaba | Michigan | 49829 | United States |
| Weisberg Cancer Treatment Center | Farmington Hills | Michigan | 48334 | United States |
| Cancer Hematology Centers - Flint | Flint | Michigan | 48503 | United States |
| Genesee Hematology Oncology PC | Flint | Michigan | 48503 | United States |
| Genesys Hurley Cancer Institute | Flint | Michigan | 48503 | United States |
| Hurley Medical Center | Flint | Michigan | 48503 | United States |
| Henry Ford Saint John Hospital - Academic | Grosse Pointe Woods | Michigan | 48236 | United States |
| Henry Ford Saint John Hospital - Breast | Grosse Pointe Woods | Michigan | 48236 | United States |
| Henry Ford Saint John Hospital - Van Elslander | Grosse Pointe Woods | Michigan | 48236 | United States |
| Allegiance Health | Jackson | Michigan | 49201 | United States |
| University of Michigan Health - Sparrow Lansing | Lansing | Michigan | 48912 | United States |
| Hope Cancer Clinic | Livonia | Michigan | 48154 | United States |
| Trinity Health Saint Mary Mercy Livonia Hospital | Livonia | Michigan | 48154 | United States |
| Henry Ford Saint John Hospital - Macomb Medical | Macomb | Michigan | 48044 | United States |
| Henry Ford Warren Hospital - Breast Macomb | Macomb | Michigan | 48044 | United States |
| Saint Mary's Oncology/Hematology Associates of Marlette | Marlette | Michigan | 48453 | United States |
| MyMichigan Medical Center Midland | Midland | Michigan | 48670 | United States |
| Henry Ford Medical Center-Columbus | Novi | Michigan | 48377 | United States |
| Hope Cancer Center | Pontiac | Michigan | 48341 | United States |
| Michigan Healthcare Professionals Pontiac | Pontiac | Michigan | 48341 | United States |
| Newland Medical Associates-Pontiac | Pontiac | Michigan | 48341 | United States |
| Trinity Health Saint Joseph Mercy Oakland Hospital | Pontiac | Michigan | 48341 | United States |
| Henry Ford Rochester Hospital | Rochester Hills | Michigan | 48309 | United States |
| MyMichigan Medical Center Saginaw | Saginaw | Michigan | 48601 | United States |
| Oncology Hematology Associates of Saginaw Valley PC | Saginaw | Michigan | 48604 | United States |
| Bhadresh Nayak MD PC-Sterling Heights | Sterling Heights | Michigan | 48312 | United States |
| MyMichigan Medical Center Tawas | Tawas City | Michigan | 48764 | United States |
| Advanced Breast Care Center PLLC | Warren | Michigan | 48088 | United States |
| Henry Ford Health Warren Hospital | Warren | Michigan | 48093 | United States |
| Henry Ford Madison Heights Hospital - Breast | Warren | Michigan | 48093 | United States |
| Henry Ford Warren Hospital - GLCMS | Warren | Michigan | 48093 | United States |
| Macomb Hematology Oncology PC | Warren | Michigan | 48093 | United States |
| Henry Ford West Bloomfield Hospital | West Bloomfield | Michigan | 48322 | United States |
| Saint Mary's Oncology/Hematology Associates of West Branch | West Branch | Michigan | 48661 | United States |
| Huron Gastroenterology PC | Ypsilanti | Michigan | 48106 | United States |
| Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus | Ypsilanti | Michigan | 48197 | United States |
| Sanford Joe Lueken Cancer Center | Bemidji | Minnesota | 56601 | United States |
| Essentia Health Saint Joseph's Medical Center | Brainerd | Minnesota | 56401 | United States |
| Fairview Ridges Hospital | Burnsville | Minnesota | 55337 | United States |
| Mercy Hospital | Coon Rapids | Minnesota | 55433 | United States |
| Essentia Health - Deer River Clinic | Deer River | Minnesota | 56636 | United States |
| Essentia Health Saint Mary's - Detroit Lakes Clinic | Detroit Lakes | Minnesota | 56501 | United States |
| Essentia Health Cancer Center | Duluth | Minnesota | 55805 | United States |
| Essentia Health Saint Mary's Medical Center | Duluth | Minnesota | 55805 | United States |
| Miller-Dwan Hospital | Duluth | Minnesota | 55805 | United States |
| Fairview Southdale Hospital | Edina | Minnesota | 55435 | United States |
| Lake Region Healthcare Corporation-Cancer Care | Fergus Falls | Minnesota | 56537 | United States |
| Essentia Health - Fosston | Fosston | Minnesota | 56542 | United States |
| Unity Hospital | Fridley | Minnesota | 55432 | United States |
| Essentia Health Hibbing Clinic | Hibbing | Minnesota | 55746 | United States |
| Fairview Clinics and Surgery Center Maple Grove | Maple Grove | Minnesota | 55369 | United States |
| Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota | 55109 | United States |
| Saint John's Hospital - Healtheast | Maplewood | Minnesota | 55109 | United States |
| Abbott-Northwestern Hospital | Minneapolis | Minnesota | 55407 | United States |
| Hennepin County Medical Center | Minneapolis | Minnesota | 55415 | United States |
| Health Partners Inc | Minneapolis | Minnesota | 55454 | United States |
| Monticello Cancer Center | Monticello | Minnesota | 55362 | United States |
| New Ulm Medical Center | New Ulm | Minnesota | 56073 | United States |
| Essentia Health - Park Rapids | Park Rapids | Minnesota | 56470 | United States |
| North Memorial Medical Health Center | Robbinsdale | Minnesota | 55422 | United States |
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota | 55416 | United States |
| Regions Hospital | Saint Paul | Minnesota | 55101 | United States |
| United Hospital | Saint Paul | Minnesota | 55102 | United States |
| Essentia Health Sandstone | Sandstone | Minnesota | 55072 | United States |
| Saint Francis Regional Medical Center | Shakopee | Minnesota | 55379 | United States |
| Lakeview Hospital | Stillwater | Minnesota | 55082 | United States |
| Sanford Thief River Falls Medical Center | Thief River Falls | Minnesota | 56701 | United States |
| Essentia Health Virginia Clinic | Virginia | Minnesota | 55792 | United States |
| Ridgeview Medical Center | Waconia | Minnesota | 55387 | United States |
| Rice Memorial Hospital | Willmar | Minnesota | 56201 | United States |
| Minnesota Oncology Hematology PA-Woodbury | Woodbury | Minnesota | 55125 | United States |
| Sanford Cancer Center Worthington | Worthington | Minnesota | 56187 | United States |
| Fairview Lakes Medical Center | Wyoming | Minnesota | 55092 | United States |
| Baptist Memorial Hospital and Cancer Center-Oxford | Oxford | Mississippi | 38655 | United States |
| Baptist Memorial Hospital and Cancer Center-Desoto | Southhaven | Mississippi | 38671 | United States |
| Saint Louis Cancer and Breast Institute-Ballwin | Ballwin | Missouri | 63011 | United States |
| Central Care Cancer Center - Bolivar | Bolivar | Missouri | 65613 | United States |
| Parkland Health Center-Bonne Terre | Bonne Terre | Missouri | 63628 | United States |
| Cox Cancer Center Branson | Branson | Missouri | 65616 | United States |
| Saint Francis Medical Center | Cape Girardeau | Missouri | 63703 | United States |
| Southeast Cancer Center | Cape Girardeau | Missouri | 63703 | United States |
| Siteman Cancer Center at Saint Peters Hospital | City of Saint Peters | Missouri | 63376 | United States |
| Siteman Cancer Center at West County Hospital | Creve Coeur | Missouri | 63141 | United States |
| Centerpoint Medical Center LLC | Independence | Missouri | 64057 | United States |
| MU Health Care Goldschmidt Cancer Center | Jefferson City | Missouri | 65109 | United States |
| Freeman Health System | Joplin | Missouri | 64804 | United States |
| Mercy Hospital Joplin | Joplin | Missouri | 64804 | United States |
| Research Medical Center | Kansas City | Missouri | 64132 | United States |
| Delbert Day Cancer Institute at PCRMC | Rolla | Missouri | 65401 | United States |
| Mercy Clinic-Rolla-Cancer and Hematology | Rolla | Missouri | 65401 | United States |
| Heartland Regional Medical Center | Saint Joseph | Missouri | 64506 | United States |
| Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri | 63670 | United States |
| Mercy Hospital Springfield | Springfield | Missouri | 65804 | United States |
| CoxHealth South Hospital | Springfield | Missouri | 65807 | United States |
| Saint Louis Cancer and Breast Institute-South City | St Louis | Missouri | 63109 | United States |
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| Siteman Cancer Center-South County | St Louis | Missouri | 63129 | United States |
| Missouri Baptist Medical Center | St Louis | Missouri | 63131 | United States |
| Siteman Cancer Center at Christian Hospital | St Louis | Missouri | 63136 | United States |
| Mercy Hospital Saint Louis | St Louis | Missouri | 63141 | United States |
| Missouri Baptist Sullivan Hospital | Sullivan | Missouri | 63080 | United States |
| BJC Outpatient Center at Sunset Hills | Sunset Hills | Missouri | 63127 | United States |
| Mercy Hospital Washington | Washington | Missouri | 63090 | United States |
| Community Hospital of Anaconda | Anaconda | Montana | 59711 | United States |
| Billings Clinic Cancer Center | Billings | Montana | 59101 | United States |
| Saint Vincent Healthcare | Billings | Montana | 59101 | United States |
| Saint Vincent Frontier Cancer Center | Billings | Montana | 59102 | United States |
| Bozeman Health Deaconess Hospital | Bozeman | Montana | 59715 | United States |
| Saint James Community Hospital and Cancer Treatment Center | Butte | Montana | 59701 | United States |
| Benefis Sletten Cancer Institute | Great Falls | Montana | 59405 | United States |
| Great Falls Clinic | Great Falls | Montana | 59405 | United States |
| Saint Peter's Community Hospital | Helena | Montana | 59601 | United States |
| Logan Health Medical Center | Kalispell | Montana | 59901 | United States |
| Saint Patrick Hospital - Community Hospital | Missoula | Montana | 59802 | United States |
| Community Medical Center | Missoula | Montana | 59804 | United States |
| Nebraska Cancer Specialists/Oncology Hematology West PC | Grand Island | Nebraska | 68803 | United States |
| Nebraska Medicine Heartland Hematology Oncology | Kearney | Nebraska | 68845 | United States |
| CHI Health Good Samaritan | Kearney | Nebraska | 68847 | United States |
| Saint Elizabeth Regional Medical Center | Lincoln | Nebraska | 68510 | United States |
| Alegent Health Immanuel Medical Center | Omaha | Nebraska | 68122 | United States |
| Hematology and Oncology Consultants PC | Omaha | Nebraska | 68122 | United States |
| Alegent Health Bergan Mercy Medical Center | Omaha | Nebraska | 68124 | United States |
| Alegent Health Lakeside Hospital | Omaha | Nebraska | 68130 | United States |
| Creighton University Medical Center | Omaha | Nebraska | 68131 | United States |
| Midlands Community Hospital | Papillion | Nebraska | 68046 | United States |
| Morristown Medical Center | Morristown | New Jersey | 07960 | United States |
| Overlook Hospital | Summit | New Jersey | 07902 | United States |
| Lovelace Medical Center-Saint Joseph Square | Albuquerque | New Mexico | 87102 | United States |
| University of New Mexico Cancer Center | Albuquerque | New Mexico | 87106 | United States |
| New Mexico Oncology Hematology Consultants | Albuquerque | New Mexico | 87109 | United States |
| Presbyterian Kaseman Hospital | Albuquerque | New Mexico | 87110 | United States |
| Presbyterian Rust Medical Center/Jorgensen Cancer Center | Rio Rancho | New Mexico | 87124 | United States |
| University of Rochester | Rochester | New York | 14642 | United States |
| Dickstein Cancer Treatment Center | White Plains | New York | 10601 | United States |
| East Carolina University | Greenville | North Carolina | 27834 | United States |
| Margaret R Pardee Memorial Hospital | Hendersonville | North Carolina | 28791 | United States |
| Sanford Bismarck Medical Center | Bismarck | North Dakota | 58501 | United States |
| Essentia Health Cancer Center-South University Clinic | Fargo | North Dakota | 58103 | United States |
| Sanford South University Medical Center | Fargo | North Dakota | 58103 | United States |
| Sanford Broadway Medical Center | Fargo | North Dakota | 58122 | United States |
| Sanford Roger Maris Cancer Center | Fargo | North Dakota | 58122 | United States |
| Essentia Health - Jamestown Clinic | Jamestown | North Dakota | 58401 | United States |
| Indu and Raj Soin Medical Center | Beavercreek | Ohio | 45431 | United States |
| Dayton Physicians LLC-Miami Valley South | Centerville | Ohio | 45459 | United States |
| Miami Valley Hospital South | Centerville | Ohio | 45459 | United States |
| Good Samaritan Hospital - Cincinnati | Cincinnati | Ohio | 45220 | United States |
| Oncology Hematology Care Inc-Kenwood | Cincinnati | Ohio | 45236 | United States |
| Bethesda North Hospital | Cincinnati | Ohio | 45242 | United States |
| TriHealth Cancer Institute-Westside | Cincinnati | Ohio | 45247 | United States |
| TriHealth Cancer Institute-Anderson | Cincinnati | Ohio | 45255 | United States |
| Cleveland Clinic Cancer Center/Fairview Hospital | Cleveland | Ohio | 44111 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Good Samaritan Hospital - Dayton | Dayton | Ohio | 45406 | United States |
| Miami Valley Hospital | Dayton | Ohio | 45409 | United States |
| Dayton Physician LLC - Englewood | Dayton | Ohio | 45415 | United States |
| Miami Valley Hospital North | Dayton | Ohio | 45415 | United States |
| Armes Family Cancer Center | Findlay | Ohio | 45840 | United States |
| Blanchard Valley Hospital | Findlay | Ohio | 45840 | United States |
| Orion Cancer Care | Findlay | Ohio | 45840 | United States |
| Atrium Medical Center-Middletown Regional Hospital | Franklin | Ohio | 45005-1066 | United States |
| Dayton Physicians LLC-Atrium | Franklin | Ohio | 45005 | United States |
| Dayton Physicians LLC-Wayne | Greenville | Ohio | 45331 | United States |
| Wayne Hospital | Greenville | Ohio | 45331 | United States |
| Cleveland Clinic Cancer Center Independence | Independence | Ohio | 44131 | United States |
| Greater Dayton Cancer Center | Kettering | Ohio | 45409 | United States |
| First Dayton Cancer Care | Kettering | Ohio | 45420 | United States |
| Kettering Medical Center | Kettering | Ohio | 45429 | United States |
| Cleveland Clinic Cancer Center Mansfield | Mansfield | Ohio | 44906 | United States |
| Hillcrest Hospital Cancer Center | Mayfield Heights | Ohio | 44124 | United States |
| North Coast Cancer Care | Sandusky | Ohio | 44870 | United States |
| Springfield Regional Cancer Center | Springfield | Ohio | 45504 | United States |
| Springfield Regional Medical Center | Springfield | Ohio | 45504 | United States |
| Cleveland Clinic Cancer Center Strongsville | Strongsville | Ohio | 44136 | United States |
| Dayton Physicians LLC - Troy | Troy | Ohio | 45373 | United States |
| Upper Valley Medical Center | Troy | Ohio | 45373 | United States |
| South Pointe Hospital | Warrensville Heights | Ohio | 44122 | United States |
| Cleveland Clinic Wooster Family Health and Surgery Center | Wooster | Ohio | 44691 | United States |
| University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | 73104 | United States |
| Integris Southwest Medical Center | Oklahoma City | Oklahoma | 73109 | United States |
| Mercy Hospital Oklahoma City | Oklahoma City | Oklahoma | 73120 | United States |
| Integris Cancer Institute of Oklahoma | Oklahoma City | Oklahoma | 73142 | United States |
| Saint Alphonsus Cancer Care Center-Baker City | Baker City | Oregon | 97814 | United States |
| Saint Charles Health System | Bend | Oregon | 97701 | United States |
| Clackamas Radiation Oncology Center | Clackamas | Oregon | 97015 | United States |
| Providence Cancer Institute Clackamas Clinic | Clackamas | Oregon | 97015 | United States |
| Bay Area Hospital | Coos Bay | Oregon | 97420 | United States |
| Providence Newberg Medical Center | Newberg | Oregon | 97132 | United States |
| Saint Alphonsus Cancer Care Center-Ontario | Ontario | Oregon | 97914 | United States |
| Providence Portland Medical Center | Portland | Oregon | 97213 | United States |
| Providence Saint Vincent Medical Center | Portland | Oregon | 97225 | United States |
| Saint Charles Health System-Redmond | Redmond | Oregon | 97756 | United States |
| Jefferson Abington Hospital | Abington | Pennsylvania | 19001 | United States |
| Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | 18103 | United States |
| Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | 18017 | United States |
| Christiana Care Health System-Concord Health Center | Chadds Ford | Pennsylvania | 19317 | United States |
| Pocono Medical Center | East Stroudsburg | Pennsylvania | 18301 | United States |
| Ephrata Cancer Center | Ephrata | Pennsylvania | 17522 | United States |
| Ephrata Community Hospital | Ephrata | Pennsylvania | 17522 | United States |
| Adams Cancer Center | Gettysburg | Pennsylvania | 17325 | United States |
| WellSpan Medical Oncology and Hematology | Hanover | Pennsylvania | 17331 | United States |
| Lehigh Valley Hospital-Hazleton | Hazleton | Pennsylvania | 18201 | United States |
| Sechler Family Cancer Center | Lebanon | Pennsylvania | 17042 | United States |
| University of Pennsylvania/Abramson Cancer Center | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | 15232 | United States |
| Penn State Health Saint Joseph Medical Center | Reading | Pennsylvania | 19605 | United States |
| Asplundh Cancer Pavilion | Willow Grove | Pennsylvania | 19090 | United States |
| WellSpan Health-York Cancer Center | York | Pennsylvania | 17403 | United States |
| WellSpan Health-York Hospital | York | Pennsylvania | 17403 | United States |
| Prisma Health Cancer Institute - Spartanburg | Boiling Springs | South Carolina | 29316 | United States |
| Prisma Health Cancer Institute - Laurens | Clinton | South Carolina | 29325 | United States |
| Prisma Health Cancer Institute - Easley | Easley | South Carolina | 29640 | United States |
| Prisma Health Cancer Institute - Butternut | Greenville | South Carolina | 29605 | United States |
| Prisma Health Cancer Institute - Faris | Greenville | South Carolina | 29605 | United States |
| Prisma Health Greenville Memorial Hospital | Greenville | South Carolina | 29605 | United States |
| Prisma Health Cancer Institute - Eastside | Greenville | South Carolina | 29615 | United States |
| Prisma Health Cancer Institute - Greer | Greer | South Carolina | 29650 | United States |
| Prisma Health Cancer Institute - Seneca | Seneca | South Carolina | 29672 | United States |
| Sanford Cancer Center Oncology Clinic | Sioux Falls | South Dakota | 57104 | United States |
| Sanford USD Medical Center - Sioux Falls | Sioux Falls | South Dakota | 57117-5134 | United States |
| Memorial Hospital | Chattanooga | Tennessee | 37404 | United States |
| Pulmonary Medicine Center of Chattanooga-Hixson | Hixson | Tennessee | 37343 | United States |
| Baptist Memorial Hospital and Cancer Center-Memphis | Memphis | Tennessee | 38120 | United States |
| Memorial GYN Plus | Ooltewah | Tennessee | 37363 | United States |
| Saint Joseph Regional Cancer Center | Bryan | Texas | 77802 | United States |
| Covenant Medical Center-Lakeside | Lubbock | Texas | 79410 | United States |
| Virginia Commonwealth University/Massey Cancer Center | Richmond | Virginia | 23298 | United States |
| Providence Regional Cancer System-Aberdeen | Aberdeen | Washington | 98520 | United States |
| PeaceHealth Saint Joseph Medical Center | Bellingham | Washington | 98225 | United States |
| Highline Medical Center-Main Campus | Burien | Washington | 98166 | United States |
| Providence Regional Cancer System-Centralia | Centralia | Washington | 98531 | United States |
| Swedish Cancer Institute-Edmonds | Edmonds | Washington | 98026 | United States |
| Saint Elizabeth Hospital | Enumclaw | Washington | 98022 | United States |
| Providence Regional Cancer Partnership | Everett | Washington | 98201 | United States |
| Saint Francis Hospital | Federal Way | Washington | 98003 | United States |
| Swedish Cancer Institute-Issaquah | Issaquah | Washington | 98029 | United States |
| Kadlec Clinic Hematology and Oncology | Kennewick | Washington | 99336 | United States |
| Providence Regional Cancer System-Lacey | Lacey | Washington | 98503 | United States |
| Saint Clare Hospital | Lakewood | Washington | 98499 | United States |
| PeaceHealth Saint John Medical Center | Longview | Washington | 98632 | United States |
| Harrison HealthPartners Hematology and Oncology-Poulsbo | Poulsbo | Washington | 98370 | United States |
| Pacific Gynecology Specialists | Seattle | Washington | 98104 | United States |
| Swedish Medical Center-Ballard Campus | Seattle | Washington | 98107 | United States |
| Kaiser Permanente Washington | Seattle | Washington | 98112 | United States |
| Swedish Medical Center-Cherry Hill | Seattle | Washington | 98122-5711 | United States |
| Swedish Medical Center-First Hill | Seattle | Washington | 98122 | United States |
| PeaceHealth United General Medical Center | Sedro-Woolley | Washington | 98284 | United States |
| Providence Regional Cancer System-Shelton | Shelton | Washington | 98584 | United States |
| Saint Michael Cancer Center | Silverdale | Washington | 98383 | United States |
| MultiCare Deaconess Cancer and Blood Specialty Center - Downtown | Spokane | Washington | 99204 | United States |
| MultiCare Deaconess Cancer and Blood Specialty Center - North | Spokane | Washington | 99218 | United States |
| MultiCare Deaconess Cancer and Blood Specialty Center - Valley | Spokane Valley | Washington | 99216 | United States |
| Franciscan Research Center-Northwest Medical Plaza | Tacoma | Washington | 98405 | United States |
| Northwest Medical Specialties PLLC | Tacoma | Washington | 98405 | United States |
| PeaceHealth Southwest Medical Center | Vancouver | Washington | 98664 | United States |
| Providence Saint Mary Regional Cancer Center | Walla Walla | Washington | 99362 | United States |
| Providence Regional Cancer System-Yelm | Yelm | Washington | 98597 | United States |
| Edwards Comprehensive Cancer Center | Huntington | West Virginia | 25701 | United States |
| Duluth Clinic Ashland | Ashland | Wisconsin | 54806 | United States |
| Northwest Wisconsin Cancer Center | Ashland | Wisconsin | 54806 | United States |
| Saint Vincent Hospital Cancer Center Green Bay | Green Bay | Wisconsin | 54301 | United States |
| Saint Vincent Hospital Cancer Center at Saint Mary's | Green Bay | Wisconsin | 54303 | United States |
| Gundersen Lutheran Medical Center | La Crosse | Wisconsin | 54601 | United States |
| University of Wisconsin Carbone Cancer Center - University Hospital | Madison | Wisconsin | 53792 | United States |
| Holy Family Memorial Hospital | Manitowoc | Wisconsin | 54221 | United States |
| Saint Vincent Hospital Cancer Center at Marinette | Marinette | Wisconsin | 54143 | United States |
| Medical College of Wisconsin | Milwaukee | Wisconsin | 53226 | United States |
| Cancer Center of Western Wisconsin | New Richmond | Wisconsin | 54017 | United States |
| Saint Vincent Hospital Cancer Center at Oconto Falls | Oconto Falls | Wisconsin | 54154 | United States |
| HSHS Saint Nicholas Hospital | Sheboygan | Wisconsin | 53081 | United States |
| Saint Vincent Hospital Cancer Center at Sturgeon Bay | Sturgeon Bay | Wisconsin | 54235-1495 | United States |
| Cheyenne Regional Medical Center-West | Cheyenne | Wyoming | 82001 | United States |
| Billings Clinic-Cody | Cody | Wyoming | 82414 | United States |
| Welch Cancer Center | Sheridan | Wyoming | 82801 | United States |
Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| FG002 | Azacitidine + Midostaurin | Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Azacitidine | Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| BG001 | Azacitidine + Nivolumab | Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| BG002 | Azacitidine +Midostaurin | Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||
| Baseline Blast Percentage | Count of Participants | Participants |
| ||||||||||||||||
| FLT3-Centrally Reviewed | Count of Participants | Participants |
| ||||||||||||||||
| Zubrod Performance Status | Zubrod sacle ranges from 0-4, higher scores reflecting greater disability 0: Fully active, able to carry on all pre-disease performance w/o restriction
| Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Overall Survival (OS) (Phase II) | Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died. | The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm). | Posted | Median | 95% Confidence Interval | months | Day of registration on study until death from any cause, assessed for up to 5 years |
|
|
| |||||||||||||||||||||||||||||||
| Primary | OS (Phase III) | Time from date of randomization on study until death from any cause with observations censored on the day of last contact for patients not known to have died. | Due to unexpected toxicities on the Azacitidine + Nivolumab arm during the first two cycles of therapy, the trial was closed early, before the phase II portions was completed and before reaching the phase III portion. | Posted | Day of registration on study until death from any cause, assessed for up to 5 years |
| ||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs | Only adverse events that are possibly, probably, or definitely related to study drugs are reported. CTCAE Version 5.0 was used for all AE reporting. | Participants who were eligible and received at least one dose of protocol treatment. | Posted | Number | Participants | Duration of treatment and follow up until death or 5 years post randomization (registration to Step 2). |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Remission Rates | #participants(ps) w comp response(resp)(CR), comp remission w incomp bld ct recovery(CRp/CRi), morphol leukemia-free state(MLFS), erythroid&neutrophil&platelet resp(HI-E,HI-N,HI-P), HI-P, marrow comp resp(CRm), stable disease(SD), no resp(NR) CR:BM blasts<5%; no circ blasts&blasts w Auer rods(AR); no extramedullary disease(ED); ANC≥1x10^9/L; plt ct≥100x10^9/L CRp/CRi:CR criteria excl residual neutropenia<1x10^9/L or ITP<100x10^9/L MLFS:BM blasts<5%; no blasts w AR, ED, hem recovery rqd HI-E:≥1.5g/dL↑Hb pretx;&RBC trans-depen ps, achieve trans independ or relevant↓RBC trans rqd HI-N:ANC↑pretx≥100%,&an absolute↑of>500/mm3 pretx HI-P:Absolute↑≥30000/mm3 pretx for ps w plt ct>20000/mm3 pretx. Ps w plt ct≤20000/mm3 pretx,↑≥100% pretx ct to plt ct>20000/mm3. Plt trans-depend ps, plt trans independ rqd CRm:CR for BM exam≤5%myeloblasts&marrow myeloblasts↓≥50%pretx SD:Not achieve≥PR, w no evidence prog NR:Not achieve CR,CRi,PR,MLFS,SD, excl ps w death in aplasia or due to indet cause | The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm). | Posted | Count of Participants | Participants | Up to 5 years |
| ||||||||||||||||||||||||||||||||||
| Other Pre-specified | OS | Will be estimated using the Kaplan-Meier method or Cox regression models. Landmark analyses of different response categories will be evaluated based on dates at which 75% and 90% of patients have achieved a response (with other quantiles analyzed as needed). | Not Posted | Day of registration on study until death from any cause, assessed for up to 5 years | Participants | |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Relapse-free Survival (RFS) | Time from the date of achievement of a remission (defined as patients achieving complete remission (CR), or CR with incomplete hematological recovery (CRi)) until the date of relapse or death from any cause; patients not known to have relapsed or died at last follow-up are censored on the date of last contact. | The analysis population includes the 17 participants who were eligible and evaluable and had complete response or complete remission with incomplete blood count recovery (CRp/CRi) (6 in the Azacitidine arm, 5 in the Azacitidine+Nivolumab arm, and 6 in the Azacitidine+Midostaurin arm). | Posted | Median | 95% Confidence Interval | months | Date of achievement of a remission until the date of relapse or death from any cause, assessed for up to 5 years |
| |||||||||||||||||||||||||||||||||
| Other Pre-specified | Event-free Survival (EFS) | Time from from the date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause; patients not known to have any of these events are censored on the date of last contact. | The analysis population includes the 76 participants who were eligible and evaluable (26 in the Azacitidine arm, 25 in the Azacitidine+Nivolumab arm, and 25 in the Azacitidine+Midostaurin arm). | Posted | Median | 95% Confidence Interval | months | Date of randomization to the first of: date of primary refractory disease; date of progressive disease; date off protocol therapy without CR or CRi; date of relapse from CR or CRi, or death from any cause, assessed for up to 5 years |
| |||||||||||||||||||||||||||||||||
| Other Pre-specified | Cumulative Incidence of Relapse Defined as Achieving CR or CRi | Cumulative incident endpoints and associations will be assessed using Cox regression models (for cause-specific hazards as appropriate). | Not Posted | Date of achievement of a remission until the date of relapse or death, assessed for up to 5 years | Participants | |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | FLT3-ITD | The prognostic effect of FLT3-ITD (positive versus negative or non-evaluable) with respect to the outcome OS will be evaluated using Cox regression models. The predictive effect of FLT3-ITD (positive versus negative/non-evaluable) with respect to the outcome of OS and the treatments of azacitdine+midostaurin versus azacitidine will be evaluated using a Cox regression model with treatment arm and FLT3-ITD as covariates and including the interaction between the two covariates. | Not Posted | Up to 5 years | Participants | |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Cytogenetic Abnormalities, Risk Categories, and Mutations in Bone Marrow | Univariate and multivariable regression models will be used to assess potential associations between outcomes (CR, OS, EFS, and RFS) and cytogenetic abnormalities and mutation status (including FLT3-ITD). Regression models including interaction terms with treatment arm will be fit. In addition to analyzing FLT3-ITD as categorical variable used in randomization stratification, we will analyze FLT3-TKD also and evaluate FLT3-ITD allelic ratio as a quantitative variable and as a binary variable using the threshold of 0.50. | Not Posted | Up to 5 years | Participants | |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Potential Control Arm Drift | Only concurrently randomized patients will be evaluated in comparisons between arms. | Not Posted | Up to 5 years | Participants |
Duration of treatment and follow up until death or 5 years post randomization (registration to Step 2).
CTCAE version 5.0 was used for reporting toxicities and SAEs. There were 25 participants in the Azacitidine arm, 25 participants in the Azacitidine + Nivolumab arm, and 23 participants in the Azacitidine + Midostaurin arm that were evaluable for AEs.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azacitidine | Patients receive azacitidine SC or IV daily on days 1-7 or on an interrupted schedule which ensures that all 7 days of therapy are received within a 12 day period. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. One participant withdrew from protocol therapy before starting treatment and is therefore included in the All-Cause Mortality but not Serious Adverse Events. | 24 | 26 | 9 | 25 | 23 | 25 |
| EG001 | Azacitidine + Nivolumab | Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. | 25 | 25 | 20 | 25 | 23 | 25 |
| EG002 | Azacitidine +Midostaurin | Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. One participant withdrew from protocol therapy before starting treatment and one participant died before starting treatment, therefore these two participants are included in the All-Cause Mortality but not Serious Adverse Events. | 23 | 25 | 17 | 23 | 22 | 23 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Disseminated intravascular coagulation | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Leukocytosis | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Atrial fibrillation | Cardiac disorders | Systematic Assessment |
| ||
| Cardiac arrest | Cardiac disorders | Systematic Assessment |
| ||
| Heart failure | Cardiac disorders | Systematic Assessment |
| ||
| Left ventricular systolic dysfunction | Cardiac disorders | Systematic Assessment |
| ||
| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Pericardial tamponade | Cardiac disorders | Systematic Assessment |
| ||
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Supraventricular tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Esophageal ulcer | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastrointestinal disorders-Other | Gastrointestinal disorders | Systematic Assessment |
| ||
| Jejunal obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Lower gastrointestinal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
| ||
| Rectal hemorrhage | Gastrointestinal disorders | Systematic Assessment |
| ||
| Small intestinal obstruction | Gastrointestinal disorders | Systematic Assessment |
| ||
| Small intestinal perforation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Typhlitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Death NOS | General disorders | Systematic Assessment |
| ||
| Edema limbs | General disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Infusion related reaction | General disorders | Systematic Assessment |
| ||
| Multi-organ failure | General disorders | Systematic Assessment |
| ||
| Non-cardiac chest pain | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Sudden death NOS | General disorders | Systematic Assessment |
| ||
| Allergic reaction | Immune system disorders | Systematic Assessment |
| ||
| Immune system disorders-Other | Immune system disorders | Systematic Assessment |
| ||
| Enterocolitis infectious | Infections and infestations | Systematic Assessment |
| ||
| Infections and infestations-Other | Infections and infestations | Systematic Assessment |
| ||
| Joint infection | Infections and infestations | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Skin infection | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Hip fracture | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Activated partial thromboplastin time prolonged | Investigations | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Cardiac troponin I increased | Investigations | Systematic Assessment |
| ||
| Ejection fraction decreased | Investigations | Systematic Assessment |
| ||
| Fibrinogen decreased | Investigations | Systematic Assessment |
| ||
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
| ||
| Acidosis | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypoglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neoplasms benign, malignant and unspecified - Other | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Encephalopathy | Nervous system disorders | Systematic Assessment |
| ||
| Intracranial hemorrhage | Nervous system disorders | Systematic Assessment |
| ||
| Ischemia cerebrovascular | Nervous system disorders | Systematic Assessment |
| ||
| Movements involuntary | Nervous system disorders | Systematic Assessment |
| ||
| Seizure | Nervous system disorders | Systematic Assessment |
| ||
| Confusion | Psychiatric disorders | Systematic Assessment |
| ||
| Delirium | Psychiatric disorders | Systematic Assessment |
| ||
| Acute kidney injury | Renal and urinary disorders | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Urinary retention | Renal and urinary disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Blood and lymphatic system disorders-Other | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Cardiac disorders-Other | Cardiac disorders | Systematic Assessment |
| ||
| Heart failure | Cardiac disorders | Systematic Assessment |
| ||
| Myocardial infarction | Cardiac disorders | Systematic Assessment |
| ||
| Sinus tachycardia | Cardiac disorders | Systematic Assessment |
| ||
| Hypothyroidism | Endocrine disorders | Systematic Assessment |
| ||
| Blurred vision | Eye disorders | Systematic Assessment |
| ||
| Eye disorders-Other | Eye disorders | Systematic Assessment |
| ||
| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Constipation | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
| ||
| Dyspepsia | Gastrointestinal disorders | Systematic Assessment |
| ||
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
| ||
| Gastrointestinal disorders-Other | Gastrointestinal disorders | Systematic Assessment |
| ||
| Mucositis oral | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Oral pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Chills | General disorders | Systematic Assessment |
| ||
| Edema limbs | General disorders | Systematic Assessment |
| ||
| Fatigue | General disorders | Systematic Assessment |
| ||
| Fever | General disorders | Systematic Assessment |
| ||
| Gait disturbance | General disorders | Systematic Assessment |
| ||
| General disorders and administration site conditio | General disorders | Systematic Assessment |
| ||
| Injection site reaction | General disorders | Systematic Assessment |
| ||
| Malaise | General disorders | Systematic Assessment |
| ||
| Non-cardiac chest pain | General disorders | Systematic Assessment |
| ||
| Pain | General disorders | Systematic Assessment |
| ||
| Infections and infestations-Other | Infections and infestations | Systematic Assessment |
| ||
| Lung infection | Infections and infestations | Systematic Assessment |
| ||
| Sinusitis | Infections and infestations | Systematic Assessment |
| ||
| Skin infection | Infections and infestations | Systematic Assessment |
| ||
| Upper respiratory infection | Infections and infestations | Systematic Assessment |
| ||
| Urinary tract infection | Infections and infestations | Systematic Assessment |
| ||
| Bruising | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Fall | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Injury, poisoning and procedural complications-Oth | Injury, poisoning and procedural complications | Systematic Assessment |
| ||
| Alanine aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Alkaline phosphatase increased | Investigations | Systematic Assessment |
| ||
| Aspartate aminotransferase increased | Investigations | Systematic Assessment |
| ||
| Blood bilirubin increased | Investigations | Systematic Assessment |
| ||
| Cardiac troponin I increased | Investigations | Systematic Assessment |
| ||
| Creatinine increased | Investigations | Systematic Assessment |
| ||
| Electrocardiogram QT corrected interval prolonged | Investigations | Systematic Assessment |
| ||
| INR increased | Investigations | Systematic Assessment |
| ||
| Lymphocyte count decreased | Investigations | Systematic Assessment |
| ||
| Neutrophil count decreased | Investigations | Systematic Assessment |
| ||
| Platelet count decreased | Investigations | Systematic Assessment |
| ||
| Serum amylase increased | Investigations | Systematic Assessment |
| ||
| Weight loss | Investigations | Systematic Assessment |
| ||
| White blood cell decreased | Investigations | Systematic Assessment |
| ||
| Anorexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypercalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperglycemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperkalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypermagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypernatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyperuricemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypoalbuminemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypocalcemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypokalemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypomagnesemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hyponatremia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Hypophosphatemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Arthritis | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Bone pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Generalized muscle weakness | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Pain in extremity | Musculoskeletal and connective tissue disorders | Systematic Assessment |
| ||
| Neoplasms benign, malignant and unspecified (incl | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| Dysgeusia | Nervous system disorders | Systematic Assessment |
| ||
| Headache | Nervous system disorders | Systematic Assessment |
| ||
| Lethargy | Nervous system disorders | Systematic Assessment |
| ||
| Peripheral sensory neuropathy | Nervous system disorders | Systematic Assessment |
| ||
| Anxiety | Psychiatric disorders | Systematic Assessment |
| ||
| Confusion | Psychiatric disorders | Systematic Assessment |
| ||
| Delirium | Psychiatric disorders | Systematic Assessment |
| ||
| Depression | Psychiatric disorders | Systematic Assessment |
| ||
| Insomnia | Psychiatric disorders | Systematic Assessment |
| ||
| Hematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Urinary frequency | Renal and urinary disorders | Systematic Assessment |
| ||
| Urinary urgency | Renal and urinary disorders | Systematic Assessment |
| ||
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Epistaxis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Postnasal drip | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Respiratory, thoracic and mediastinal disorders-Ot | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Sore throat | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Alopecia | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Dry skin | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Pruritus | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Purpura | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Rash maculo-papular | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Skin and subcutaneous tissue disorders-Other | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Hot flashes | Vascular disorders | Systematic Assessment |
| ||
| Hypertension | Vascular disorders | Systematic Assessment |
| ||
| Hypotension | Vascular disorders | Systematic Assessment |
| ||
| Thromboembolic event | Vascular disorders | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Leukemia Committee Statistician | SWOG Statistics and Data Management Center | 2066674623 | amoseley@fredhutch.org |
| Jun 5, 2024 |
| Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D009190 | Myelodysplastic Syndromes |
| D000077428 | GATA2 Deficiency |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D003561 | Cytarabine |
| D000077209 | Decitabine |
| D007267 | Injections |
| C059539 | midostaurin |
| D000077594 | Nivolumab |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
| D001087 | Arabinonucleosides |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Black |
|
| Asian |
|
| Unknown |
|
| >=20% (AML) |
|
| Mutated FLT3-ITD |
|
| 2-4 |
|
|
|
|
| Azacitidine + Nivolumab |
Patients receive azacitidine as in Arm A and nivolumab IV over 30-60 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| OG002 | Azacitidine +Midostaurin | Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
| Azacitidine +Midostaurin |
Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
|
|
| Azacitidine +Midostaurin |
Patients receive azacitidine as in Arm A and midostaurin orally (PO) twice daily (BID) on days 8-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
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