Refractory Multiple Myeloma, Relapse Multiple Myeloma
Conditions
Keywords
CAR-T, Chimeric antigen receptor T-cell therapy, CAR Therapy
Brief summary
This is a multicenter phase II, open-label study evaluating the efficacy and safety of belantamab mafodotin maintenance in participants with relapsed and/or refractory multiple myeloma (RRMM) who have received commercially available anti-BCMA CAR-T-cell therapy. Subjects will be enrolled 60-130 days after chimeric antigen receptor T-cell therapy (CAR-T) and receive belantamab mafodotin as maintenance therapy. Each maintenance cycle will have a duration of 56 days (+/- three days) and belantamab mafodotin will be administered at a dose of 2.5 mg/kg IV on day 1 of each cycle.
Detailed description
INTERVENTION DESCRIPTION: Subjects will receive belantamab mafodotin as maintenance therapy. Belantamab mafodotin will be administered IV over approximately 30 minutes at the recommended dose of 2.5 mg/kg IV over 30 minutes on day 1 of every eight-week (+/- three days) cycle for a maximum of 12 cycles. Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or end of study (maximum of 12 cycles), whichever occurs first. Dose interruptions or reductions may be required to address potential drug-associated toxicities. The dose to be administered will be based on actual body weight calculated at baseline. However, if the change in body weight is greater than 10%, the dose will be recalculated based on the actual body weight at the time of dosing. The dose may be reduced to address toxicity.
Interventions
DRUGBelantamab mafodotin
Belantamab mafodotin will be administered IV over approximately 30 minutes at the recommended dose of 2.5 mg/kg IV over 30 minutes on day 1 of every eight-week (+/- three days) cycle for a maximum of 12 cycles. Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or end of study (maximum of 12 cycles), whichever occurs first.
Sponsors
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of multiple myeloma with measurable disease (serum M-protein ≥ 0.5 g/dL or urine M-protein ≥200 mg/24 hour or involved serum-free light chain ≥10 mg/dL provided that the ratio of involved/uninvolved light chain is abnormal) prior to receiving CAR-T. Patients with no biochemically measurable disease before CAR-T may be enrolled if bidirectionally measurable plasmacytomas or bone marrow plasmacytomas \>10% are present prior to CAR-T infusion (sites must explicitly identify these patients to the Medical College of Wisconsin Multisite Team upon enrollment, as only four of these patients will be permitted on study, after which no future patients will be permitted to be enrolled). 2. Received at least three prior therapies (including a PI, immunomodulatory drugs (IMiD), and anti-cluster of differentiation 38 antibody (anti-CD38 antibody) ) given before CAR-T, and has not progressed/relapsed after receiving CAR-T therapy. 3. Achieved at least stable disease (SD) to CAR-T therapy and remained progression free after anti-BCMA CAR-T administration until enrollment (this requirement is also necessary prior administration of first study drug). 4. Voluntary consent (per single Institutional Review Board (sIRB) requirements) 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 subject at any time without prejudice to future medical care. 5. Age ≥ 18 years. 6. Life expectancy ≥ six months. 7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 8. Creatinine clearance (CrCl) ≥ 30 mL/minute, either measured or calculated using a standard formula (e.g., Modification of Diet in Renal Disease (MDRD) Study equation; Cockcroft and Gault). 9. Adequate hepatic function evidenced by aspartate aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 2.5 x ULN, bilirubin ≤ 1.5 x upper limit of the normal range (ULN) (isolated bilirubin ≥1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). 10. Adequate bone marrow function evidenced by hemoglobin ≥8 g/dL, platelets ≥75,000/mm3 (without transfusion of platelets in the prior seven days) and absolute neutrophil count ≥1,500/mm\^3 (growth factors are allowed during screening, but not within seven days prior to obtaining this result). 11. Spot urine (albumin/creatinine ratio) \< 500 mg/g (56 mg/mmol) OR urine dipstick negative/trace (if ≥ 1+ only eligible if confirmed \< 500 mg/g (56 mg/mmol) by albumin/creatinine ratio (spot urine from first void). 12. Patients with prior allotransplant more than one year prior to enrollment, with or without ongoing topical treatment for skin GVHD (without evidence of active GVHD) are eligible (refer to
Exclusion criteria
). 13. Female participants: Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP). OR Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), preferably with low user dependency during the intervention period and for four months after the last dose of belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on cycle 1 day 1 (C1D1) and agree to use a highly effective method of contraception during the study and for four months after the last dose of belantamab mafodotin. 14. Male participants: Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following from the time of first dose of study until six months after the last dose of belantamab mafodotin to allow for clearance of any altered sperm: Refrain from donating sperm. AND either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. OR Must agree to use contraception/barrier as detailed below: • Agree to use a male condom, even if they have undergone a successful vasectomy and female partner to use an additional highly effective contraceptive method with a failure rate of \<1% per year as described in when having sexual intercourse with a WOCBP (including pregnant females).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Patients With 12-month Progression-free Survival. | 12 months | The primary endpoint of the study is the 12-month progression-free survival (PFS) with time counted from the CAR-T infusion conditional on being alive and progression-free at day +90 post CAR-T. An event will be defined as documented progression or death for any cause, subjects without an event will be censored at the last date known to be alive without progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Belantamab Mafodotin Belantamab mafodotin is an intravenous drug.
Belantamab mafodotin: Belantamab mafodotin will be administered IV over approximately 30 minutes at the recommended dose of 2.5 mg/kg IV over 30 minutes on day 1 of every eight-week (+/- three days) cycle for a maximum of 12 cycles. Maintenance therapy with belantamab mafodotin will continue until progressive disease (PD), death, unacceptable toxicity, withdrawal of consent or end of study (maximum of 12 cycles), whichever occurs first. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Belantamab Mafodotin |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
The Number of Patients With 12-month Progression-free Survival.
The primary endpoint of the study is the 12-month progression-free survival (PFS) with time counted from the CAR-T infusion conditional on being alive and progression-free at day +90 post CAR-T. An event will be defined as documented progression or death for any cause, subjects without an event will be censored at the last date known to be alive without progression.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Belantamab Mafodotin | The Number of Patients With 12-month Progression-free Survival. | 1 Participants |