Clinical trial NCT04680468: Study of Belantamab Mafodotin as Pre- and Post-autologous Stem Cell Transplant and Maintenance for Multiple Myeloma
Official title: Phase 2 Study of Belantamab Mafodotin as Pre- and Post-autologous Stem Cell Transplant Consolidation and Maintenance for Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Myeloma
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2020-12-23
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-institution, single-arm, phase 2 study in which belantamab mafodotin (GSK2857916), an antibody-drug conjugate targeting B-cell maturation antigen (BCMA), will be administered to patients with multiple myeloma prior to and following high-dose melphalan and autologous stem cell transplantation (ASCT), in conjunction with standard lenalidomide maintenance. We hypothesize that administration of belantamab mafodotin as part of autologous stem cell transplant consolidation and maintenance will be safe, well tolerated, and efficacious in comparison to historical data.


Eligibility criteria: Inclusion Criteria:

* Subjects must have started therapy for active multiple myeloma within 12 months of enrollment.
* Subjects must have an ECOG performance status of 0-2.
* Have received no more than 2 prior lines of induction therapy (induction regimen not specified by protocol), with no prior progressive disease by International Myeloma Working Group (IMWG) criteria.
* Must be in at least a partial response (PR) but not in a complete response (CR) or better after at least 4 cycles of induction therapy, per IMWG consensus criteria.
* Eligible by institutional criteria to receive melphalan at a dose of 200 mg/m2.
* Eligible to receive lenalidomide maintenance therapy post-ASCT.
* Adequate bone marrow and organ function at enrollment

Exclusion Criteria:

* Participant must not have used an investigational drug or approved systemic anti-myeloma therapy (including systemic steroids) within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug.
* Participant must not have received treatment with a monoclonal antibody within 28 days of receiving the first dose of study drug
* Participant must not be simultaneously enrolled in any interventional clinical trial
* Participant must not have amyloidosis or POEMS syndrome.
* Participants must not be pregnant or lactating.
* Participant must not have current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, severe hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) or hepatobiliary involvement of malignancy is acceptable if otherwise meets entry criteria
* Participant must not have any evidence of active mucosal or internal bleeding
* History of an active renal condition (infection, requirement for dialysis or any other condition that could affect subject's safety). Subjects with isolated proteinuria resulting from MM are eligible, provided they fulfill criteria given in Section 6.1.
* Participant must not have evidence of cardiovascular risk
* Participants must not have any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions (including lab abnormalities) that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures.
* Participant must not have invasive malignancies other than disease under study, unless the second malignancy has been definitively treated or has been medically stable for at least 2 years and, in the opinion of the principal investigator, will not affect the evaluation of the effects of clinical trial treatment.
* Participants must not have an active infection requiring antibiotic treatment.
* Any major surgery within the last 4 weeks prior to enrollment.
* Participant must not have current corneal epithelial disease except mild changes in corneal epithelium
* Participant must not have known immediate or delayed hypersensitivity reaction or idiosyncratic reactions to belantamab mafodotin or drugs chemically related to belantamab mafodotin, or any of the components of the study treatment
* Participant must not have evidence for active hepatitis B infection (i.e. positive hepatitis B surface antigen or nucleic acid-based testing) at screening or within 3 months prior to first dose of belantamab mafodotin. Subjects with positive testing for hepatitis B core antibody but no evidence for active infection by nucleic acid-based testing may enroll if they agree to hepatitis B prophylactic therapy and monitoring for HBV re-activation for the duration of the study.
* Participant must not have positive hepatitis C antibody test result or positive hepatitis C RNA test result at screening or within 3 months prior to first dose of study treatment. NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative hepatitis C RNA test is obtained.
* Participant must not have evidence of active HIV infection. Participants with positive HIV serologies who are on stable active anti-retroviral therapy, have CD4 count \> 200 cells/µL, and have no detectable HIV virus by nucleic acid-based testing at screening or within 3 months prior to first dose of study drug may be eligible after discussion with medical director and/or principal investigator.

Primary outcomes:
measure: MRD (minimal residual disease) negativity rate
timeFrame: 12 months post-ASCT
Secondary outcomes:
measure: Frequency of treatment-related adverse events
timeFrame: through study completion, approximately 3 years
measure: Dose reductions
timeFrame: through study completion, approximately 3 years
measure: Dose delays
timeFrame: through study completion, approximately 3 years
measure: MRD Negativity Rate
timeFrame: at 3 and 24 months post-ASCT
measure: Overall response rate
timeFrame: through study completion, approximately 3 years
measure: Very good partial response (VGPR) or better rate
timeFrame: through study completion, approximately 3 years
measure: Complete response (CR) or better rate
timeFrame: through study completion, approximately 3 years
measure: Progression-free survival
timeFrame: through study completion, approximately 3 years
measure: Overall survival
timeFrame: through study completion, approximately 3 years
measure: Stem cell yield
timeFrame: Following stem cell mobilization, about 6 weeks after enrollment
measure: Stem cell collection days
timeFrame: Following stem cell mobilization, about 6 weeks after enrollment
measure: Hematopoietic reconstitution post-ASCT
timeFrame: up to 30 days post-ASCT
measure: Change from Baseline in Health-related quality of life (HRQoL) as assessed by Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) questionnaire
timeFrame: baseline through study completion, approximately 3 years.
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Adam Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: