Pomalidomide and Dexamethasone With or Without Ixazomib in Treating Patients With Relapsed Multiple Myeloma
- Conditions
- Multiple Myeloma in Relapse
- Interventions
- Registration Number
- NCT02004275
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
This randomized phase I/II trial studies the side effects and best dose of pomalidomide and ixazomib when given together with dexamethasone and to see how well pomalidomide and dexamethasone with or without ixazomib works in treating patients with multiple myeloma that has come back. Biological therapies, such as pomalidomide and dexamethasone, may stimulate the immune system in different ways and stop cancer cells from growing. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether pomalidomide and dexamethasone are more effective with or without ixazomib in treating multiple myeloma.
- Detailed Description
PRIMARY OBJECTIVES:
I. To establish the maximum tolerated dose (MTD) for combination therapy pomalidomide/dexamethasone/ixazomib. (Phase I) II. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves progression-free survival (PFS) relative to pomalidomide/dexamethasone. (Phase II)
SECONDARY OBJECTIVES:
I. To determine dose-limiting toxicities (DLTs). (Phase I) II. To analyze type and grade of all serious adverse events (SAEs). (Phase I) III. To analyze type and grade of all adverse events (AEs). (Phase I) IV. To analyze the reason for and incidence of dose modifications/omissions/delays. (Phase I) V. To assess preliminary evidence of clinical efficacy. (Phase I) VI. To assess whether the overall response rate (ORR), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent CR (sCR) rate differ with respect to treatment regimen. (Phase II) VII. To assess the clinical benefit rate (CBR: minimal response \[MR\] + ORR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) VIII. To assess the disease control rate (DCR: stable disease \[SD\] + CBR) for pomalidomide/dexamethasone/ixazomib compared to pomalidomide/dexamethasone. (Phase II) IX. For those patients achieving a PR or better, we will assess whether the combination of pomalidomide/dexamethasone/ixazomib increases the duration of response (DOR) compared to pomalidomide/dexamethasone. (Phase II) X. To assess whether the combination of pomalidomide/dexamethasone/ixazomib improves overall survival (OS) compared to those taking pomalidomide/dexamethasone alone. (Phase II) XI. To assess time to next treatment (TNT) for patients taking pomalidomide/dexamethasone/ixazomib compared to those on pomalidomide/dexamethasone. (Phase II) XII. To evaluate the safety of pomalidomide/dexamethasone/ixazomib compared with pomalidomide/dexamethasone. (Phase II) XIII. For patients on the pomalidomide/dexamethasone arm who opt to cross-over to the pomalidomide/dexamethasone/ixazomib arm, assessment of response rate (ORR, CBR, DCR), DOR, TNT, PFS and OS will be evaluated from date of cross-over. (Phase II) XIV. To determine if baseline level of perceived fatigue and overall quality of life (QOL) is associated with OS. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of pomalidomide and ixazomib followed by a phase II study.
After completion of study treatment, patients are followed up every 4 weeks until disease progression and then every 3 months for 3 years.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 118
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm I (pomalidomide, dexamethasone) dexamethasone Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II. Arm I (pomalidomide, dexamethasone) pomalidomide Patients receive pomalidomide PO QD on days 1-21 and dexamethasone PO QD on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving disease progression may cross over to Arm II. Arm II (pomalidomide, dexamethasone, ixazomib) pomalidomide Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (pomalidomide, dexamethasone, ixazomib) ixazomib Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Arm II (pomalidomide, dexamethasone, ixazomib) dexamethasone Patients receive pomalidomide, dexamethasone, and ixazomib as in Phase I. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Pomalidomide and Ixazomib, Determined According to Incidence of Dose Limiting Toxicity (DLT) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I) 28 days For this protocol, dose-limiting toxicity (DLT) will be defined by the following adverse events at least possibly related to study therapy: Grade 3 or higher non-hematologic toxicity, with the following exceptions: Alopecia is not expected but would not be considered a DLT. Nausea, vomiting and diarrhea will only be considered a DLT if it cannot be adequately managed with optimal supportive care. Grade 3 or 4 hyperglycemia due to dexamethasone will only be considered a DLT if it cannot be controlled with appropriate therapy Grade 4 hematologic toxicity, with the following exceptions: Grade 4 lymphopenia is expected with this regimen and will not be construed as a DLT. Grade 4 neutropenia will only be considered a DLT if it lasts longer than 7 days despite appropriate supportive care. Grade 4 thrombocytopenia will only be considered a DLT if it lasts longer than 7 days or is associated with greater then or equal to grade 3 bleeding event
Progression Free Survival (PFS) (Phase II) 3 years progression-free survival (PFS), defined as the time from randomization to the date the International Myeloma Working Group (IMWG) criteria for disease progression is met. If a patient initiates another anti-cancer treatment prior to disease progression, they will be censored at the date of initiation of this treatment. Patients will be randomized to treatment using the Pocock-Simon algorithm balancing the distribution of the following stratification factors between the two treatment arms: 1) ISS 1-2 disease vs. ISS 3 disease (current ISS stage based off screening beta 2 microglobulin and albumin) 2) High risk cytogenetics features: yes vs. no High risk cytogenetics features include: del(1p), gain of 1q, t(4;14), t(14;16), t(14; 20), del(17p) 3) Prior treatment with a proteasome inhibitor: yes vs. no
- Secondary Outcome Measures
Name Time Method Incidence and Type of Dose Limiting Toxicities (DLTs) Graded According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Phase I) 44.5 months These events are reported in the adverse events section of this report.
Disease Control Rate (DCR), Defined as Stable Disease (SD) and Better According to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II) 42 days Proportion of patients that went two of more cycles of treatment without discontinuing treatment for progression or intolerability.
Clinical Benefit Rate (CBR) 3 years Disease response status is based on the IMWG criteria being held for two consecutive evaluations at least 4 weeks apart. Clinical benefit rate (CBR) is defined as proportion of patients with minimal response (MR) and better according to International Myeloma Working Group (IMWG) Uniform Response Criteria (Phase II)
Duration of Response (DOR), Calculated for All Patients Achieving an Objective Response, Partial Response (PR) or Better (Phase II) Up to 3 years Time to Next Treatment (TNT) (Phase II) Up to 3 years post-registration Incidence of Dose Reductions/Delays (Phase I) 39 months Overall Response Rate (ORR) 3 years ORR is defined as partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR) according to International Myeloma Working Group (IMWG) Uniform Response Criteria
Baseline Level of Perceived Fatigue and QOL, Assessed Using the Registration Fatigue/Uniscale Assessment Form (Phase II) baseline Pre-treatment patient-report of fatigue and overall quality of life (based on a 10-point Likert scale). A higher number indicates a better quality of life where 10 is the best outcome and 0 is the worst.
Response Rates (Overall Response Rate (ORR), Clinical Benefit Rate (CBR), Disease Control Rate (DCR) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II) Up to 3 years Overall Survival (OS) (Phase II) 2 years Overall survival was analyzed from the time of registration to the date of death or last known date living. Due to median OS time not being reached due to lack of deaths at the time of this report by either arm, the 2 year OS rate has been reported. This analysis censors living patients at 2 years.
Incidence, Type and Severity of Adverse Events, Graded According to National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE) Version 4.0 (Phase II) 92 months The count of paitents that experenced an adverse event is reported in this section. A full table of these events is reported in the adverse event section of this report.
Progression Free Survival (PFS) for All Patients on the Pomalidomide/Dexamethasone Arm at the Time of Cross-over to Pomalidomide/Dexamethasone/Ixazomib (Phase II) Up to 3 years post-registration (at crossover)
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Trial Locations
- Locations (336)
Anchorage Associates in Radiation Medicine
🇺🇸Anchorage, Alaska, United States
Anchorage Radiation Therapy Center
🇺🇸Anchorage, Alaska, United States
Alaska Breast Care and Surgery LLC
🇺🇸Anchorage, Alaska, United States
Alaska Oncology and Hematology LLC
🇺🇸Anchorage, Alaska, United States
Alaska Regional Hospital
🇺🇸Anchorage, Alaska, United States
Alaska Women's Cancer Care
🇺🇸Anchorage, Alaska, United States
Anchorage Oncology Centre
🇺🇸Anchorage, Alaska, United States
Katmai Oncology Group
🇺🇸Anchorage, Alaska, United States
Providence Alaska Medical Center
🇺🇸Anchorage, Alaska, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
🇺🇸Burbank, California, United States
Scroll for more (326 remaining)Anchorage Associates in Radiation Medicine🇺🇸Anchorage, Alaska, United States