Clinical Trial 18217

Cancer Type: Malignant Hematology
Interventions:Alkeran (Melphalan); Bortezomib; FK506 (Tacrolimus); Ixazomib (Ninlaro); Melphalan; Not Applicable; PS-341 (Bortezomib); Placebo; Tacrolimus; Velcade (Bortezomib); fludarabine (Fludarabine phosphate); methotrexate

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Taiga Nishihori

Overview

Study Title

Multicenter Phase II, Double-blind Placebo Controlled Trial of Maintenance Ixazomib after Allogeneic Hematopoietic Stem Cell Transplantation for High Risk Multiple Myeloma

Summary

The purpose of this study to learn if adding Ixazomib to the participant's maintenance treatment (chemotherapy) works better to control their disease than placebo (pill that doesn't have any drugs, like a sugar pill).

Objective

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 GVHD, chronic GVHD, best disease response rates, disease progression, transplant related mortality, overall survival, rates of Grade 3 or higher toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, incidence of infections, and health-related quality of life.

Inclusion Criteria

  • Age ≥ 18 years and ≤ 65 years at the time of enrollment.
  • Participants must meet ONE of the criteria outlined in either A, B, C or D: (A.) Patients with high risk multiple myeloma in partial response (PR) or better at the time of enrollment with no prior progression and within 18 months from initiation of systemic anti-myeloma therapy, which may include single or planned tandem autologous HSCT. [High risk is defined by the presence of any one of the following: 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) ; and elevated beta-2 microglobulin (≥ 5.5 mg/L at diagnosis), detected at any time prior to enrollment]; or (B.) Patients with high risk multiple myeloma (criterion 3a above) in very good partial response (VGPR) or better at the time of enrollment with at most 1 prior progression within 18 months from initiation of systemic anti-myeloma therapy in patients with NO prior autologous HSCT; or (C.) Patients with standard risk multiple myeloma in VGPR or better at the time of enrollment with 1 prior progression within 18 months from a single or planned tandem autologous HSCT; or (D.) Patients with primary plasma cell leukemia in VGPR or better at the time of enrollment with no prior disease progression and within 18 months prior to initiation of anti-myeloma therapy which may include single or planned tandem autologous transplant .
  • Must have a related or unrelated peripheral blood stem cell donor that meet one of the following criteria: (A.) A sibling donor who is a 6/6 match at HLA-A and -B (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 (B.) 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 (C.) An unrelated donor who is an 8/8 match at HLA-A, -B, -C, 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.
  • Cardiac function: Ejection fraction > 40%.
  • Estimated creatinine clearance greater than 40 mL/minute (using the Cockcroft-Gault formula and actual body weight).
  • Adequate pulmonary function, according to study guidelines.
  • Adequate liver function, according to study guidelines.
  • Males and females must follow study specific contraception guidelines.
  • Able to comply with the study visit schedule and other protocol requirements.

  • Exclusion Criteria

  • Karnofsky Performance Score less than 70%
  • Prior allogeneic HSCT
  • 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 preemptive/prophylactic administration of donor lymphocytes.
  • Central Nervous System (CNS) involvement with multiple myeloma defined as CSF positivity for plasma cells or a parenchymal CNS plasmacytoma.
  • 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.
  • Seropositive for the human immunodeficiency virus (HIV).
  • Active Hepatitis B or C determined by serology and/or NAAT.
  • Hypersensitivity to bortezomib, boron or mannitol.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Sensory peripheral neuropathy > Grade 2.
  • Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
  • Females who are lactating or pregnant
  • Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent > 5 years previously will be allowed. Cancer treated with curative intent > Multi-organ involvement by amyloidosis or evidence of amyloidosis-related organ dysfunction
  • Failure to have fully recovered (i.e. no toxicities > Grade 1) from the reversible effects of prior chemotherapy.
  • Serious medical or psychiatric illness likely to interfere with participation on this clinical study.
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
  • Have received radiation therapy within 3 weeks before transplant. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
  • Unable or unwilling to adhere to the study assessment schedule.