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Closed due to slow enrollment
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This is a research study to be done at multiple sites in participants with advanced acute myeloid leukemia (AML) that have a mutation in Fms-like tyrosine kinase-3 internal tandem duplications (FLT3-ITD). This study is to learn more about an investigational drug, quizartinib, being tested with the anti-cancer medicine CPX-351 (also called Vyxeosâ„¢), which is approved and widely used to treat AML.
The purpose of this study is to assess the safety, tolerability and survival of patients receiving the combination of CPX-351 and quizartinib.
This is an open-label, two-part Phase II clinical trial in patients with relapsed or refractory FLT3-ITD mutation-positive acute myeloid leukemia (AML). The study is designed to assess the safety and tolerability as well as the efficacy of administering CPX-351 (cytarabine:daunorubicin liposome complex) with quizartinib. CPX-351 is a formulation of two drugs, cytarabine and daunorubicin, that is administered as the first part of treatment to get rid of as many leukemia cells in your bone marrow as possible. Quizartinib is an investigational drug made of a protein that inhibits FLT3 and will be given after CPX-351 has been given. The plan for administration is divided into three phases: induction, consolidation, and maintenance.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CPX-351 and Quizartinib treatment | Experimental | Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CPX-351 | Drug | Given during the induction and consildation phase and will consist of 44 mg/m^2 daunorubicin with 100 mg/m^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Treatment Related Adverse Events After Taking CPX-351 and Quizartinib | Counting the number of patients with treatment related adverse events as a measure of safety and tolerability. | Collected during treatment and for 30 days after last dose, approximately 35 total days for the 1 patient treated. |
| Number of Patients With an Overall Response Taking CPX-351 and Quizartinib | Overall response is defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL) | from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Median Time to Platelet Count Recovery | Time to platelet recovery is defined as the time to when the peripheral blood platelet count is >50, 000/ μL | from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months |
| Median Time to Absolute Neutrophil Count (ANC) Recovery |
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Inclusion Criteria:
Written informed consent form (ICF), according to local guidelines, signed by the patient or by a legal guardian prior to the performance of any study-related screening procedures.
Patients with the following types of AML with >5% blasts:
First-line therapy must have contained a standard induction chemotherapy (e.g. 7+3, FLAG-IDA, FLAG, CLAG, MEC, hypomethylating agent with venetoclax) with or without receiving a prior FLT3 inhibitor (e.g. midostaurin) or multi-tyrosine kinase inhibitor (e.g. sorafenib). All patients who relapsed after an alloHCT are included, except patients with active graft-versus-host disease (GVHD) requiring >10 mg prednisone.
Patients must be able to swallow and retain oral medication.
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 (Appendix A).
Adequate renal and hepatic parameters (aspartate aminotransferase [AST], alanine aminotransferase [ALT] ≤2.5 institutional upper limit of normal [ULN]; total bilirubin ≤2.0 institutional ULN; serum creatinine [Cr] ≤2.0). In patients with suspected liver infiltration, ALT can be ≤5 institutional ULN.
Exclusion Criteria:
Acute promyelocytic leukemia (t[15;17])
Female patients who are lactating or have a positive serum pregnancy test during the screening period. Female patients of childbearing potential who are not willing to employ highly effective birth control (as defined in Appendix C of protocol) from screening to 6 months following the last dose of CPX-351 and/or quizartinib.
Evidence of active and uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of active infection progression are present. This is assessed by the site clinicians, including an infectious disease consulting physician, if requested by the Principal Investigator (PI), regarding adequacy of therapy. These infections include, but are not limited to:
History of hypersensitivity to cytarabine, daunorubicin, or an FLT3 inhibitor
Any patients with known significant impairment in gastrointestinal (GI) function or GI disease that my significantly alter the absorption of quizartinib.
Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Uncontrolled or significant cardiovascular disease, including any of the following:
History of New York Heart Association Class 3 or 4 heart failure
Prior anthracycline (or equivalent) cumulative exposure ≥368 mg/m2 daunorubicin (or equivalent)
Any serious underlying medical condition that, in the opinion of the Investigator or Medical Monitor, would impair the ability to receive or tolerate the planned treatment.
Patients with inadequate adequate pulmonary function will be excluded. Inadequate pulmonary function is defined as requiring supplemental O2, or diffusing capacity of the lungs for carbon monoxide [DLCO] <40%.
Active acute or chronic GVHD requiring prednisone >10 mg or equivalent.
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| Name | Affiliation | Role |
|---|---|---|
| Michael Tees, MD, MPH | Colorado Blood Cancer Institute | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Colorado Blood Cancer Institute | Denver | Colorado | 80218 | United States | ||
| HCA Midwest |
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| ID | Title | Description |
|---|---|---|
| FG000 | CPX-351 and Quizartinib Treatment | Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m^2 daunorubicin with 100 mg/m^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase. |
| 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 | Aug 10, 2020 |
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| Quizartinib | Drug | Given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase. |
|
Time to neutrophil recovery is defined as the time to when the peripheral blood ANC is ≥500/μL |
| from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months |
| Number of Patients Proceeding to an Allogeneic Hematopoietic Cell Transplantation (alloHCT) | Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) following treatment in induction and consolidation therapies. | up to 60 days after consolidation therapy |
| Median Time to Disease Progression | Time to disease progression, confirmed by bone marrow biopsy. | from diagnosis of relapse or refractory AML until disease progression for up to 2 years post treatment |
| Event-free Survival Time | Defined as the number of days until evidence of PD by bone marrow biopsy/aspirate, or death, regardless of cause. Patients who are alive without a disease response assessment of relapsed disease will be censored at the last adequate disease assessment date. Patients without a disease response assessment will be censored at the first date of treatment. | from day 1 for up to 4 years |
| Overall Survival (OS) | Overall survival is defined as the time from the first date of treatment until death as a result of any cause. For OS time, patients that have not died or are lost to follow-up will be censored at the date the patient was last known to be alive or the date of last contact. | Up to 8 months |
| Number of Patients Who Develop Late Responses | Late responses as defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL | up to 4 years |
| Number of Patients Who Can Receive Consolidation and Maintenance Therapy | Patients who proceed through induction to next stages of consolidation and maintenance | approximately 3 months |
| Treatment-related Mortality Rate | As determined by the number of treatment related deaths during study treatment | Observed during treatment and for 30 days after last dose, so approximately 35 days for the 1 patient treated. |
| Percentage of Patients Who Achieve a PR or Molecular Complete Remission | A PR is defined as persistent disease by morphology but with a >50% reduction in the blast count/cellularity ratio compared to the most recent BM biopsy prior to treatment. A molecular complete remission is defined as no evidence of disease by bone marrow biopsy/aspirate by morphology, immunohistochemistry, or flow cytometry, and FLT3 mutation by MRD analysis. | from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment |
| Mean Elapsed Time for Patients to Achieve Molecular CR | The mean time to achievement of a complete morphologic CR with persistent disease detected by flow or molecular minimal residual disease (MRD) analysis. | From Date of First Treatment to up to 2 years |
| Quizartinib Tolerability After Allogeneic Hematopoietic Cell Transplantation (alloHCT) or Donor Lymphocyte Infusion (DLI) | Defined as the number of patients who received quizartinib and proceeded to alloHCT or DLI as part of this study and had treatment-related adverse events | From Date of First Treatment, up to 2 years |
| Kansas City |
| Missouri |
| 64132 |
| United States |
| Tennessee Oncology | Nashville | Tennessee | 37203 | United States |
| St. David's South Austin Medical Center | Austin | Texas | 78704 | United States |
| Texas Transplant Institute | San Antonio | Texas | 78229 | United States |
| COMPLETED |
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| NOT COMPLETED |
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Only 1 patient was enrolled and treated before study was terminated due to slow accrual
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| ID | Title | Description |
|---|---|---|
| BG000 | CPX-351 and Quizartinib Treatment | Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m^2 daunorubicin with 100 mg/m^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| 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 | Number of Patients With Treatment Related Adverse Events After Taking CPX-351 and Quizartinib | Counting the number of patients with treatment related adverse events as a measure of safety and tolerability. | 1 patient was treated on study and did have treatment-related adverse events | Posted | Count of Participants | Participants | Collected during treatment and for 30 days after last dose, approximately 35 total days for the 1 patient treated. |
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| Primary | Number of Patients With an Overall Response Taking CPX-351 and Quizartinib | Overall response is defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL) | Patients must have received at least one dose of CPX-351 or quizartinib, who have an adequate baseline disease assessment, and an adequate post-baseline assessment and who discontinue due to death or PD prior to their first assessment. The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed. | Posted | from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment |
| ||||||||||||||||||||||||||||||
| Secondary | Median Time to Platelet Count Recovery | Time to platelet recovery is defined as the time to when the peripheral blood platelet count is >50, 000/ μL | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed. | Posted | from cycle 1 Day 1 (each cycle is 28 days) for up to 24 months |
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| Secondary | Median Time to Absolute Neutrophil Count (ANC) Recovery | Time to neutrophil recovery is defined as the time to when the peripheral blood ANC is ≥500/μL | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed. | Posted | from Cycle 1 Day 1 (each cycle is 28 days) for up to 24 months |
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| Secondary | Number of Patients Proceeding to an Allogeneic Hematopoietic Cell Transplantation (alloHCT) | Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) following treatment in induction and consolidation therapies. | The patient discontinued treatment early and didn't follow induction and consolidation therapies to reach the alloHCT. Therefore no patients were analyzed. | Posted | up to 60 days after consolidation therapy |
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| Secondary | Median Time to Disease Progression | Time to disease progression, confirmed by bone marrow biopsy. | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline evaluation was done. Therefore, no patients were analyzed. | Posted | from diagnosis of relapse or refractory AML until disease progression for up to 2 years post treatment |
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| Secondary | Event-free Survival Time | Defined as the number of days until evidence of PD by bone marrow biopsy/aspirate, or death, regardless of cause. Patients who are alive without a disease response assessment of relapsed disease will be censored at the last adequate disease assessment date. Patients without a disease response assessment will be censored at the first date of treatment. | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib. No post-baseline assessment was performed and was therefore censored at Date of First Treatment. Therefore, no patients were analyzed. | Posted | from day 1 for up to 4 years |
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| Secondary | Overall Survival (OS) | Overall survival is defined as the time from the first date of treatment until death as a result of any cause. For OS time, patients that have not died or are lost to follow-up will be censored at the date the patient was last known to be alive or the date of last contact. | Only 1 patient was treated. | Posted | Number | months | Up to 8 months |
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| Secondary | Number of Patients Who Develop Late Responses | Late responses as defined by the International Working Group response criteria (Cheson et al 2003) as having a complete remission (CR) - a complete morphologic response with complete blood count recovery absolute neutrophil count ≥1000/μL and platelet count ≥100,000/μL) or a complete morphologic response with an incomplete blood count recovery (CRi) - absolute neutrophil count <1000/μL and/or platelet count <100,000/μL | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed. | Posted | up to 4 years |
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| Secondary | Number of Patients Who Can Receive Consolidation and Maintenance Therapy | Patients who proceed through induction to next stages of consolidation and maintenance | The patient discontinued treatment early and didn't follow induction and consolidation therapies to reach the alloHCT or maintenance therapy. | Posted | Count of Participants | Participants | approximately 3 months |
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| Secondary | Treatment-related Mortality Rate | As determined by the number of treatment related deaths during study treatment | The 1 enrolled patient did not have a treatment-related death. | Posted | Count of Participants | Participants | Observed during treatment and for 30 days after last dose, so approximately 35 days for the 1 patient treated. |
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| Secondary | Percentage of Patients Who Achieve a PR or Molecular Complete Remission | A PR is defined as persistent disease by morphology but with a >50% reduction in the blast count/cellularity ratio compared to the most recent BM biopsy prior to treatment. A molecular complete remission is defined as no evidence of disease by bone marrow biopsy/aspirate by morphology, immunohistochemistry, or flow cytometry, and FLT3 mutation by MRD analysis. | The 1 patient that was enrolled discontinued study treatment in Cycle 1 prior to receiving Quizartinib, no post-baseline assessment was done. Therefore, no patients were analyzed. | Posted | from cycle 1 day 1 (each cycle is 28 days) until disease progression for up to 2 years post treatment |
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| Secondary | Mean Elapsed Time for Patients to Achieve Molecular CR | The mean time to achievement of a complete morphologic CR with persistent disease detected by flow or molecular minimal residual disease (MRD) analysis. | The 1 patient enrolled discontinued in Cycle 1. No post-baseline assessment therefore no patients analyzed | Posted | From Date of First Treatment to up to 2 years |
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| Secondary | Quizartinib Tolerability After Allogeneic Hematopoietic Cell Transplantation (alloHCT) or Donor Lymphocyte Infusion (DLI) | Defined as the number of patients who received quizartinib and proceeded to alloHCT or DLI as part of this study and had treatment-related adverse events | The 1 patient enrolled discontinued the study prior to receiving their first dose of quizartinib. Therefore no patients analyzed. | Posted | From Date of First Treatment, up to 2 years |
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Collected for 30 days after last dose, so approximately 35 days for the 1 patient treated.
All patients who received at least one dose of protocol treatment were followed for safety. Adverse events and serious adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CPX-351 and Quizartinib Treatment | Participants with FLT3 mutation positive AML will be given CPX-351 followed by quizartinib in three phases: induction, consolidation, and maintenance. CPX-351: To be given during the induction and consolidation phase and will consist of 44 mg/m^2 daunorubicin with 100 mg/m^2 cytarabine administered intravenously on Days 1, 3, and 5 during induction phase and Days 1 and 3 of consolidation phase. Quizartinib: To be given during induction, consolidation, and maintenance phases and will be taken orally at a dose of 30mg on Days 8-21 of induction phase, Days 6-21 of consolidation phase, and daily in maintenance phase. | 1 | 1 | 0 | 1 | 1 | 1 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Chills | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Electrocardiogram QT prolonged | Investigations | MedDRA (Unspecified) | Non-systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Insomnia | Psychiatric disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Mucosal inflammation | General disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (Unspecified) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Sarah Cannon Development Innovations, LLC | Sarah Cannon Development Innovations, LLC | 844-710-6157 | CANN.InnovationsMedical@sarahcannon.com |
| Apr 11, 2022 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| C000629812 | CPX-351 |
| C544967 | quizartinib |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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