29 Jul Allogeneic Hematopoietic Stem Cell Transplantation With Ixazomib for High Risk Multiple Myeloma (BMT CTN 1302)
Full Study Title: Allogeneic Hematopoietic Stem Cell Transplantation With Ixazomib for High Risk Multiple Myeloma (BMT CTN 1302)
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.
- Age ≥ 18 years and ≤ 65 years at the time of enrollment.
- Patients must meet ONE of the criteria outlined in either a, b, c OR d:
- 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
- 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
- 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
- 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 .
- 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 -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
- 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)
- Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) ≥ 40% (adjusted for hemoglobin) and forced expiratory volume in one second (FEV1) ≥ 50%
- Liver function: total bilirubin < 2x the upper limit of normal and alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 2.5x the upper normal limit (Patients with Gilbert’s Disease are permitted to exceed the defined bilirubin value of 2x the upper limit of normal, however measurements of direct bilirubin should be done to confirm this diagnosis).
- Female subjects (unless postmenopausal for at least 1 year before the screening visit, or surgically sterilized), agree to practice two (2) effective methods of contraception at the same time, or agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception) through 90 days after the last dose of maintenance therapy (see Section 2.6.2 for definition of postmenopausal).
- Male subjects (even if surgically sterilized) must agree to one of the following: practice effective barrier contraception (see Section 220.127.116.11 for list of barrier methods), or practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of from the time of signing the informed consent through 90 days after last dose of maintenance therapy.
- Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
- Able to comply with the study visit schedule and other protocol requirements.
- Karnofsky Performance Score < 70%
- Prior allogeneic HSCT
- 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 preemptive/prophylactic administration of donor lymphocytes (as per section 2.5.2)
- Central Nervous System (CNS) involvement with multiple myeloma defined as 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 NAAT.
- Patients with 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.
- Patients with > grade 2 sensory peripheral neuropathy.
- Myocardial infarction within 6 months prior to enrollment or New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), 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.
- Female patients 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 < 5 years, which is in remission, will be reviewed on a case-by-case basis by the Protocol Officer or one of the Protocol Chairs.
- Failure to have fully recovered (i.e. no toxicities > Grade 1) from the reversible effects of prior chemotherapy.
- Patient with serious medical of 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.
- Patients who 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.
- Patients unable or unwilling to adhere to the study assessment schedule.
Study ID: NCT02440464
Medical College of Wisconsin
Mary Horowitz, MD
Parameswaran Hari, MD