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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2010-01139 | Other Identifier | NCI/CTRP |
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RATIONALE: Drugs used in chemotherapy, such as azacitidine and dexamethasone, work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Giving azacitidine together with lenalidomide and dexamethasone may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with lenalidomide and low-dose dexamethasone in treating patients with relapsed or refractory multiple myeloma.
PRIMARY OBJECTIVES:
Define the highest tolerated low dose (HTLD) and safety of azacitidine given at low but increasing doses up to 50mg/m2 twice a week concurrently with Glomerular filtration rate (GFR)-adjusted lenalidomide and low dose dexamethasone in patients with relapsed or refractory multiple myeloma.
SECONDARY OBJECTIVES:
OUTLINE:
This is a phase I, dose-escalation study of azacitidine followed by a phase II study.
Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 3 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A - Azacitidine/Lenalidomide/Dexamethasone | Experimental | Dose Level (DL) 1 - Azacitidine 30mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week DL 2 - Azacitidine 40mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week DL 3 - Azacitidine 30mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week DL 4 - Azacitidine 40mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week DL 5 - Azacitidine 50mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients (with GFR > 60 ml/min) receive azacitidine subcutaneously 1 or 2x per weekly and oral Dexamethasone 1x weekly starting on day 1. Patients receive oral lenalidomide 1x daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
|
| Arm B - Chronic Kidney Disease (CDK) Cohort | Experimental | DL (-1) - Azacitidine 30mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week DL 1 - Azacitidine 40mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week DL 2 - Azacitidine 50mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week Patients (with GFR 30-59 ml/min Chronic Kidney Disease (CKD)) receive azacitidine subcutaneously 1 or 2x per weekly and oral dexamethasone 1x weekly starting on day 1. Patients receive oral lenalidomide 1x daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| azacitidine | Drug | Given by subcutaneous injection (SC) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I: Highest Tolerated Low Dose (HTLD) | Azacitidine given at low but increasing doses up to 50mg/m2 twice a week. Maximum tolerated dose reported. | During the first 28-day cycle |
| Measure | Description | Time Frame |
|---|---|---|
| Percent of Participants With Clinical Benefit and Response According to International Response Criteria | Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. |
| Measure | Description | Time Frame |
|---|---|---|
| Changes in Global Gene Expression | The RNA harvested from myeloma cells before and after the first cycle of therapy at the HTLD level will furthermore be used to identify changes in global gene expression using the Illumina® HT12 array. | before and after the first cycle of therapy |
| Quantify the Activity of Azacitidine Inactivating Enzyme Cytidine Deaminase (CDA) |
Inclusion Criteria:
Understand and voluntarily sign an informed consent form
Able to adhere to the study visit schedule and other protocol requirements
Refractory or relapsed multiple myeloma
Measurable disease defined as at least one of the following: Serum m-spike ≥ 1g/dL, urine m-spike ≥ 200mg/24hrs, serum free light chains ≥ 100mg/L (provided the kappa/lambda ratio is abnormal), or bone marrow plasma cells ≥ 30%
Previous therapy with IMiDâ„¢ compounds (thalidomide, lenalidomide, pomalidomide), proteasome inhibitors (bortezomib, carfilzomib), and corticosteroids must be discontinued at least 14 days before entry onto this study.
Previous cytotoxic chemotherapy (e.g. alkylating chemotherapy, anthracyclines, and vinca alkaloids), radiation therapy to the pelvis, and any experimental therapy other than carfilzomib or pomalidomide must have been discontinued at least 28 days prior to entry onto this study.
Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at study entry.
Laboratory test results within these ranges:
All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.
Females of childbearing potential (FCBP)must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method at the same time, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin) if no additional risk factor for venous thromboembolic event (VTE) other than myeloma diagnosis according to IMW guidelines
Able to take low molecular weight heparin or warfarin if ≥ 1 additional risk factor for VTE according to IMW guidelines
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Frederic Reu | Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center | Principal Investigator |
| Ehsan Malek, MD | University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center | Cleveland | Ohio | 44106 | United States | ||
The 11 phase II participants were a separate population from phase I
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (GFR>=60mL/Min) Dose Level DL 1 | Azacitidine (AZA) 30mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Azacitidine/Lenalidomide/Dexamethasone Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Phase I |
|
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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 | Jul 16, 2015 |
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| lenalidomide | Drug | Given orally |
|
|
| dexamethasone | Drug | Given orally |
|
|
| DNA methylation analysis | Other | Correlative studies |
|
| gene expression analysis | Other | Correlative studies |
|
| bone marrow aspiration | Other | Correlative studies |
|
| immunohistochemistry staining method | Other | Correlative studies |
|
|
| reverse transcriptase-polymerase chain reaction | Other | Correlative studies |
|
|
| flow cytometry | Other | Correlative studies |
|
| at 6 months |
| Percent of Participants With Clinical Benefit and Response According to International Response Criteria | Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. | at 12 months |
| Median Progression-free Survival (PFS) | Median PFS, measured in months from study entry to progression as defined by international response criteria or death of any cause, whichever comes first | Up to 3 years |
| Overall Survival | Overall survival will be measured from study entry to death from any cause - median months survival will be reported | up to 3 years |
Plasma from peripheral blood draws will be used to quantify the activity of CDA using an HPLC method.The enzymatic activity is determined by comparison of cytidine deamination achieved by plasma samples with deamination achieved by incubation of cytidine with dilutions of pure CDA enzyme standards. |
| at 6 months |
| Promoter Demethylation and Gene Reactivation | Promoter demethylation and gene reactivation will be measured at least at the HTLD level using the Illumina® HumanMethylation27 BeadChip array on CD138 purified and CD34 purified cells obtained from bone marrow aspirates | within 7 days before treatment start and at the end of cycle #1 |
| CD34+ Cell Yield and Time to Neutrophil and Platelet Recovery | CD34+ cell yield will be calculated based on flow cytometry of mononuclear cells harvested following stem cell mobilization. Time to neutrophil (> 1,000/mm3) and platelet (> 100,000/mm3) recovery will be counted from the day of stem cell infusion (=day 0) | after cycle 1 (28 days) |
| Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center |
| Cleveland |
| Ohio |
| 44195 |
| United States |
| FG001 | Arm A (GFR>=60mL/Min) Dose Level 2 | Azacitidine 40mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| FG002 | Arm A (GFR>=60mL/Min) Dose Level 3 | Azacitidine 30mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| FG003 | Arm A (GFR>=60mL/Min) Dose Level 4 | Azacitidine 40mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| FG004 | Arm A (GFR>=60mL/Min) Dose Level 5 | Azacitidine 50mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| FG005 | Arm B (GFR 30-59mL/Min - CKD) Dose Level -1 | Azacitidine 30mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| FG006 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 1 | Azacitidine 40mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week |
| FG007 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 2 | Azacitidine 50mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week |
| FG008 | Phase II Arm A or B GFR >= 30mL/Min Expansion Dose (50 BIW) | Azacitidine 50mg/m2 2x week + Lenalidomide (10mg if CKD, 25mg if non-CKD) d1-21 every 28d + Dexamethasone 40mg once a week |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Phase II - Expansion Phase |
|
Participants who signed consent and were put on study
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (GFR>=60mL/Min) Dose Level DL 1 | Azacitidine (AZA) 30mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Azacitidine/Lenalidomide/Dexamethasone Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. lenalidomide: Given orally dexamethasone: Given orally DNA methylation analysis: Correlative studies gene expression analysis: Correlative studies bone marrow aspiration: Correlative studies immunohistochemistry staining method: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies flow cytometry: Correlative studies |
| BG001 | Arm A (GFR>=60mL/Min) Dose Level 2 | Azacitidine 40mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity lenalidomide: Given orally dexamethasone: Given orally DNA methylation analysis: Correlative studies gene expression analysis: Correlative studies bone marrow aspiration: Correlative studies immunohistochemistry staining method: Correlative studies reverse transcriptase-polymerase chain reaction: Correlative studies flow cytometry: Correlative studies |
| BG002 | Arm A (GFR>=60mL/Min) Dose Level 3 | Azacitidine 30mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| BG003 | Arm A (GFR>=60mL/Min) Dose Level 4 | Azacitidine 40mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| BG004 | Arm A (GFR>=60mL/Min) Dose Level 5 | Azacitidine 50mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| BG005 | Arm B (GFR 30-59mL/Min - CKD) Dose Level -1 | Azacitidine 30mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. |
| BG006 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 1 | Azacitidine 40mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week |
| BG007 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 2 | Azacitidine 50mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week |
| BG008 | Arm A or B GFR >= 30mL/ Min Expansion Dose (50 BIW) | Azacitidine 50mg/m2 2x week + Lenalidomide (10mg if CKD, 25mg if non-CKD) d1-21 every 28d + Dexamethasone 40mg once a week |
| BG009 | 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, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | 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 | Phase I: Highest Tolerated Low Dose (HTLD) | Azacitidine given at low but increasing doses up to 50mg/m2 twice a week. Maximum tolerated dose reported. | Participants in phase 1 portion of study | Posted | Number | mg/m^2 | During the first 28-day cycle |
|
|
| |||||||||||||||||||||||||||||
| Secondary | Percent of Participants With Clinical Benefit and Response According to International Response Criteria | Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. | Response-evaluable participants. Data from different dose levels were combined for the analysis as pre-specified in the study protocol | Posted | Number | percentage of participants | at 6 months |
| |||||||||||||||||||||||||||||||
| Secondary | Percent of Participants With Clinical Benefit and Response According to International Response Criteria | Percent of participants with response according to international response criteria (>= PR) and percent of participants with clinical benefit response (>= minor response according to adapted EBMT criteria). Determined with serum and 24 hour urine protein electrophoresis, and as appropriate, supplemented by immunofixation, serum free light chain assay, and bone marrow examination. Response before high dose melphalan and autologous stem cell transplant will also be confirmed by two separate blood and 24 hour urine tests between the last dose of combination therapy and the first dose of the mobilizing agent. | Response-evaluable participants | Posted | Number | percentage of participants | at 12 months |
| |||||||||||||||||||||||||||||||
| Secondary | Median Progression-free Survival (PFS) | Median PFS, measured in months from study entry to progression as defined by international response criteria or death of any cause, whichever comes first | Evaluable participants who received treatment | Posted | Median | 95% Confidence Interval | months | Up to 3 years |
|
| |||||||||||||||||||||||||||||
| Secondary | Overall Survival | Overall survival will be measured from study entry to death from any cause - median months survival will be reported | Evaluable participants who received treatment | Posted | Median | 95% Confidence Interval | months | up to 3 years |
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| |||||||||||||||||||||||||||||
| Other Pre-specified | Changes in Global Gene Expression | The RNA harvested from myeloma cells before and after the first cycle of therapy at the HTLD level will furthermore be used to identify changes in global gene expression using the Illumina® HT12 array. | Not Posted | before and after the first cycle of therapy | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Quantify the Activity of Azacitidine Inactivating Enzyme Cytidine Deaminase (CDA) | Plasma from peripheral blood draws will be used to quantify the activity of CDA using an HPLC method.The enzymatic activity is determined by comparison of cytidine deamination achieved by plasma samples with deamination achieved by incubation of cytidine with dilutions of pure CDA enzyme standards. | Not Posted | at 6 months | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | Promoter Demethylation and Gene Reactivation | Promoter demethylation and gene reactivation will be measured at least at the HTLD level using the Illumina® HumanMethylation27 BeadChip array on CD138 purified and CD34 purified cells obtained from bone marrow aspirates | Not Posted | within 7 days before treatment start and at the end of cycle #1 | Participants | ||||||||||||||||||||||||||||||||||
| Other Pre-specified | CD34+ Cell Yield and Time to Neutrophil and Platelet Recovery | CD34+ cell yield will be calculated based on flow cytometry of mononuclear cells harvested following stem cell mobilization. Time to neutrophil (> 1,000/mm3) and platelet (> 100,000/mm3) recovery will be counted from the day of stem cell infusion (=day 0) | Not Posted | after cycle 1 (28 days) | Participants |
Up to 3 years from study entry
Participants who started treatment on study were followed for Adverse Events. Number of participants at risk on Arm B Dose Level -1 is 0 because no participants were accrued to this dose level.
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 | Arm A (GFR>=60mL/Min) Dose Level DL 1 | Azacitidine (AZA) 30mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Azacitidine/Lenalidomide/Dexamethasone Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 3 | 3 | 0 | 3 | 3 | 3 |
| EG001 | Arm A (GFR>=60mL/ Min) Dose Level 2 | Azacitidine 40mg/m2 1x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 3 | 3 | 0 | 3 | 1 | 3 |
| EG002 | Arm A (GFR>=60mL/ Min) Dose Level 3 | Azacitidine 30mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 4 | 4 | 2 | 4 | 2 | 4 |
| EG003 | Arm A (GFR>=60mL/ Min) Dose Level 4 | Azacitidine 40mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 5 | 6 | 2 | 6 | 2 | 6 |
| EG004 | Arm A (GFR>=60mL/ Min) Dose Level 5 | Azacitidine 50mg/m2 2x week + Lenalidomide 25mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 6 | 6 | 1 | 6 | 3 | 6 |
| EG005 | Arm B (GFR 30-59mL/Min - CKD) Dose Level -1 | Azacitidine 30mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week Patients receive azacitidine subcutaneously once or twice weekly and oral dexamethasone once weekly starting on day 1. Patients also receive oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses. Patients then continue to receive lenalidomide as maintenance therapy. Treatment continues in the absence of disease progression or unacceptable toxicity. | 0 | 0 | 0 | 0 | 0 | 0 |
| EG006 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 1 | Azacitidine 40mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week | 3 | 3 | 1 | 3 | 1 | 3 |
| EG007 | Arm B (GFR 30-59mL/Min - CKD) Dose Level 2 | Azacitidine 50mg/m2 2x week + Lenalidomide 10mg d1-21 every 28d + Dexamethasone 40mg once a week | 5 | 6 | 1 | 6 | 4 | 6 |
| EG008 | Arm A or B GFR >= 30mL/ Min Expansion Dose (50 BIW) | Azacitidine 50mg/m2 2x week + Lenalidomide (10mg if CKD, 25mg if non-CKD) d1-21 every 28d + Dexamethasone 40mg once a week | 10 | 11 | 1 | 11 | 9 | 11 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Esophagitis | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Pain | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Confusion | Psychiatric disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Edema limbs | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Fatigue | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Fever | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Injection site reaction | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Pain | General disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Creatinine increased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Platelet count decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| White blood cell decreased | Investigations | CTCAE v4.0 | Non-systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Itching scalp | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE v4.0 | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jason Valent | Cleveland Clinic, Case Comprehensive Cancer Center | +1 216-445-7238 | VALENTJ3@ccf.org |
| May 5, 2020 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 17, 2016 | Jul 7, 2020 | ICF_001.pdf |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001374 | Azacitidine |
| D000077269 | Lenalidomide |
| D003907 | Dexamethasone |
| D002123 | Calcium Dobesilate |
| D019175 | DNA Methylation |
| D020869 | Gene Expression Profiling |
| D007150 | Immunohistochemistry |
| D020133 | Reverse Transcriptase Polymerase Chain Reaction |
| D005434 | Flow Cytometry |
| 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 |
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D001557 | Benzenesulfonates |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D001190 | Arylsulfonates |
| D017739 | Arylsulfonic Acids |
| D013451 | Sulfonic Acids |
| D013456 | Sulfur Acids |
| D013457 | Sulfur Compounds |
| D008745 | Methylation |
| D000478 | Alkylation |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D008660 | Metabolism |
| D055614 | Genetic Phenomena |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D006651 | Histocytochemistry |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D006652 | Histological Techniques |
| D007158 | Immunologic Techniques |
| D016133 | Polymerase Chain Reaction |
| D021141 | Nucleic Acid Amplification Techniques |
| D002469 | Cell Separation |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|
|
|
|