Clinical Trials /

Study of Belantamab Mafodotin as Pre- and Post-autologous Stem Cell Transplant and Maintenance for Multiple Myeloma

NCT04680468

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: UPCC 37420
  • SECONDARY ID: IRB#844252
  • NCT ID: NCT04680468

Conditions

  • Myeloma

Interventions

DrugSynonymsArms
Belantamab mafodotinGSK2857916Belantamab mafodotin

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Belantamab mafodotinExperimentalPatients receive Belantamab mafodotin 2.5 mg/kg by intravenous infusion on day -42 relative to autologous stem cell infusion (day 0), on day +60, and every 90 days thereafter, for up to 2 years following ASCT.
  • Belantamab mafodotin

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 stringent complete response
             (sCR) 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MRD (minimal residual disease) negativity rate
Time Frame:12 months post-ASCT
Safety Issue:
Description:Percentage of participants who have achieved minimal residual disease (MRD) negativity by next-generation sequencing (NGS) at 12 months post-autologous stem cell transplant (ASCT)

Secondary Outcome Measures

Measure:Frequency of treatment-related adverse events
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Percentage of participants who develop adverse and serious adverse events, including ocular adverse events.
Measure:Dose reductions
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:The percentage of participants who require reduction of the dose of belantamab mafodotin will be assessed
Measure:Dose delays
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:The percentage of participants who require a delay in dosing of belantamab mafodotin will be assessed
Measure:MRD Negativity Rate
Time Frame:at 3 and 24 months post-ASCT
Safety Issue:
Description:Percentage of participants who have achieved minimal residual disease (MRD) negativity by next-generation sequencing (NGS) at 3 and 24 months post-autologous stem cell transplant (ASCT)
Measure:Overall response rate
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Percentage of participants who achieve partial response (PR) or better, as assessed by International Myeloma Working Group (IMWG) criteria.
Measure:Very good partial response (VGPR) or better rate
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Percentage of participants who achieve VGPR or better, as assessed by IMWG criteria.
Measure:Complete response (CR) or better rate
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Percentage of participants who achieve CR or stringent CR, as assessed by IMWG criteria.
Measure:Progression-free survival
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Time from enrollment until progression of disease by IMWG criteria, or death, whichever occurs first
Measure:Overall survival
Time Frame:through study completion, approximately 3 years
Safety Issue:
Description:Time from enrollment until death from any cause
Measure:Stem cell yield
Time Frame:Following stem cell mobilization, about 6 weeks after enrollment
Safety Issue:
Description:The number of days required to collect sufficient autologous peripheral blood stem cells to proceed to ASCT will be assessed
Measure:Stem cell collection days
Time Frame:Following stem cell mobilization, about 6 weeks after enrollment
Safety Issue:
Description:: The number of days required to collect sufficient autologous peripheral blood stem cells to proceed to ASCT will be assessed
Measure:Hematopoietic reconstitution post-ASCT
Time Frame:up to 30 days post-ASCT
Safety Issue:
Description:The number of days until neutrophil and platelet recovery post-ASCT (defined as absolute neutrophil count >1000 cells/mcl and platelet count >50000 cells/mcl, respectively) will be assessed
Measure:Change from Baseline in Health-related quality of life (HRQoL) as assessed by Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM) questionnaire
Time Frame:baseline through study completion, approximately 3 years.
Safety Issue:
Description:The FACT-MM questionnaire is a 41 item questionnaire measuring physical, social/family, emotional, and functional well-being, as well as additional concerns

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Last Updated

December 23, 2020