Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib After Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma (BMT CTN 1302)

National Heart, Lung, and Blood Institute (NHLBI)15 sites in 1 country57 target enrollmentAugust 2015

ConditionsMultiple Myeloma

InterventionsAllogeneic HSCT Fludarabine Melphalan Bortezomib Ixazomib Placebo

Overview

Phase: Phase 2
Intervention: Allogeneic HSCT
Conditions: Multiple Myeloma
Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
Enrollment: 57
Locations: 15
Primary Endpoint: Percentage of Participants With Progression-Free Survival
Status: Completed
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is designed to compare progression-free survival (PFS) from randomization among patients randomized on the BMT CTN 1302 protocol, "Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib after Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma". It is hypothesized that Ixazomib maintenance therapy will result in improved PFS in patients with high-risk multiple myeloma following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) compared to placebo.

Detailed Description

The study is designed as a Phase II, multi-center double-blind trial that randomizes patients with high risk Multiple Myeloma to Ixazomib maintenance or placebo 60-120 days after allogeneic HSCT. The primary objective of this randomized trial is to compare progression free survival from randomization as a time to event endpoint between patients randomized to Ixazomib maintenance or placebo. Secondary objectives are to describe for each treatment arm: rates of grade II-IV and III-IV Graft-Versus-Host-Disease (GVHD), chronic GVHD, best disease response rates, disease progression, transplant related mortality, overall survival, rates of Grade ≥ 3 toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, incidence of infections, and health-related quality of life.

Registry

clinicaltrials.gov

Start Date

August 2015

End Date

October 1, 2020

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

National Heart, Lung, and Blood Institute (NHLBI)

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must meet one of the following disease criteria:
•a. Patients with high risk multiple myeloma in partial response (PR) or better with no prior progression and are ≤ 24.0 months after autologous hematopoietic cell transplantation (HCT) (single or planned tandem), or are ≤ 24.0 months after initiation of systemic anti-myeloma therapy for patients without prior autologous HCT; or
•i. High risk is defined by the presence of any one of the following detected at any time prior to enrollment: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1(1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling (GEP)
•b. Patients with high risk multiple myeloma (see criterion 2.a.i. above) in very good partial response (VGPR) or better with 1 prior progression which occurred ≤ 24.0 months after autologous HCT (single or planned tandem), or ≤ 24.0 months after initiation of systemic anti-myeloma therapy for patients without prior autologous HCT; or
•i. Patients with one prior progression without measurable monoclonal paraprotein at the time of disease progression or relapse (\< 1.0 g/dl in serum or \< 200 mg/24hrs in urine) may be considered to have met VGPR criteria if \< 5% plasma cells in bone marrow and ≥ 90% decrease in the difference between involved and uninvolved free light chain (FLC) levels from baseline (time of progression/relapse).
•ii. In patients with immunoglobulin G (IgG) kappa multiple myeloma (MM) receiving daratumumab: International Myeloma Working Group criteria for VGPR may not be achieved since daratumumab is known to increase the IgG kappa spike. In such cases the FLC and marrow may be used to establish VGPR, as above, with prior approval from the protocol co-chairs.
•c. Patients with standard risk multiple myeloma in VGPR or better (see criteria 2.b.i. and 2.b.ii. above) at the time of enrollment with 1 prior progression ≤ 24.0 months from single or planned tandem autologous HCT; or d. Patients with primary plasma cell leukemia in VGPR or better with no prior disease progression and are ≤ 18.0 months after autologous HCT, or are ≤ 18.0 months after initiation of anti-myeloma therapy without prior autologous HCT.
•Patients must have a related or unrelated peripheral blood stem cell donor that meet one of the following criteria:
•A sibling donor who is a 6/6 match at HLA-A and -B (intermediate or higher resolution) and -DR Beta 1 (DRB1) (at high resolution using DNA-based typing) and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation OR
•A related donor (other than sibling) who is a 8/8 match for HLA-A, -B, -C (at intermediate or higher resolution) and -DRB1 (at high resolution using DNA-based typing) and must be willing to donate peripheral blood stem cells and meet institutional criteria for donation OR

Exclusion Criteria

•Karnofsky Performance Score \< 70%
•Prior allogeneic HCT
•Patient with purely non-secretory multiple myeloma \[absence of monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by the use of conventional electrophoresis and immunofixation techniques and the absence of involved serum free light chain \> 100 mg/L\].
•Planned pre-emptive/prophylactic administration of donor lymphocytes (as per section 2.5.2)
•Central Nervous System (CNS) involvement with multiple myeloma defined as cerebrospinal fluid (CSF) positivity for plasma cells or a parenchymal CNS plasmacytoma
•Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
•Presence of fluid collection (ascites, pleural, or pericardial effusion) that interferes with methotrexate clearance or makes methotrexate use contraindicated.
•Patients seropositive for the human immunodeficiency virus (HIV).
•Patient with active Hepatitis B or C determined by serology and/or nucleic acid amplification test (NAAT).
•Patients with hypersensitivity to bortezomib, boron or mannitol.

Intervention: Placebo

Outcomes

Primary Outcomes

Percentage of Participants With Progression-Free Survival

Time Frame: 12 months and 21 months post-randomization

The primary endpoint compares progression-free survival as a time to event endpoint from randomization between patients randomized to ixazomib and placebo maintenance in high risk multiple myeloma. Participants are considered a failure of the primary endpoint if they die or suffer from disease progression or if they initiate non-protocol anti-myeloma therapy. Disease progression was evaluated using the International Uniform Response Criteria. Participants must meet one of the criteria for disease progression specified in the protocol. The time to this event is the time from randomization to progression, death, or initiation of non-protocol anti myeloma therapy whichever comes first. The Kaplan-Meier estimator was used to estimate progression-free survival during the 2 year post-transplant follow-up period. Participants who were event-free at two years post-transplant are censored at that time.

Secondary Outcomes

Percentage of Participants With Disease Progression(12 months and 21 months post-randomization)
Percentage of Participants With Overall Survival (OS)(12 months and 21 months post-randomization)
Percentage of Participants With Chronic GVHD(12 months and 21 months post-randomization)
Percentage of Participants With Acute GVHD (Grades III-IV)(100 days post-randomization)
Medical Outcomes Study (MOS) - Short Form 36 (SF-36) Score(Randomization, 6 months post-randomization, 24 months post-transplant)
Percentage of Participants With Toxicities Post-randomization by Toxicity Type(2 years post-randomization)
Functional Assessment of Cancer Therapy (FACT) - Bone Marrow Transplant (BMT) Total Score(Randomization, 6-months post-randomization, 24 months post-transplant)
Percentage of Participants With Best Response to Treatment After Randomization(2 years post-transplant)
Percentage of Participants With Response to Treatment(18 months and 24 months post-transplant)
Percentage of Participants With Toxicities Post-randomization by Time Point(6, 12 and 18 months post-randomization)
Percentage of Participants With Infections Post-randomization by Infection Type(2 years post-randomization)
Percentage of Participants With Treatment-Related Mortality (TRM)(12 months and 21 months post-randomization)
Percentage of Participants With Infections Post-randomization by Time Point(6, 12 and 18 months post-randomization)