Combination Treatment of Belantamab Mafodotin and Venetoclax in Treatment of Relapsed and Refractory T(11;14) Multiple Myeloma

NCT05853965 | Recruiting Phase 1 DMC

• 2 other identifiers: BELI(E)VE Trial2021-001413-37
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

Brief Summary

The goal of this clinical trial is to learn about the safety and efficacy of the drug combination belantamab mafodotin and venetoclax, with or without the addition of dexamethasone, in patients with relapsed/refractory multiple myeloma bearing the translocation t(11;14)

Conditions

Multiple Myeloma; Multiple Myeloma in Relapse

Keywords

t(11;14); venetoclax; belantamab mafodotin; multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Recommended Phase II dose (RP2D)

  Establishment of Recommended Phase II dose (RP2D), Evaluation of safety profile, including maximum tolerated dose

  approx. 9 months

Secondary Outcomes (4)

• Overall Response Rate

  through study completion, an average of 2 years

• Minimal residual disease (MRD) negativity

  through study completion, an average of 2 years

• Progression free survival (PFS)

  through study completion, an average of 2 years

• Duration of response (DOR)

  through study completion, an average of 2 years

Study Arms (4)

Cohort 1

EXPERIMENTAL

Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 400mg QD

Drug: Belantamab mafodotin, Venetoclax

Cohort 2

EXPERIMENTAL

Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 800mg QD

Drug: Belantamab mafodotin, Venetoclax

Cohort 3

EXPERIMENTAL

Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 400mg QD Dexamethasone 40mg Q1W (20mg for subjects ≥ 75 years)

Drug: Belantamab mafodotin, Venetoclax

Cohort 4

EXPERIMENTAL

Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 800mg QD Dexamethasone 40mg Q1W (20mg for subjects ≥ 75 years)

Drug: Belantamab mafodotin, Venetoclax

Interventions

Belantamab mafodotin, Venetoclax DRUG

Belantamab mafodotin (IV) Venetoclax (PO)

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be ≥ 18 years of age.
• Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Subjects must voluntarily sign and date an in-formed consent form
• Subjects must have had documented multiple myeloma requiring treatment as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow \> 10% and/or presence of a biopsy proven plasmacytoma at some point in their disease history requiring treatment according diag-nostic criteria (IMWG updated criteria 2014, Rajkumar et al. 2014) with measurable dis-ease at screening (serum M-protein \> 500 mg/dL or urine M protein 200 mg/24h, in case of oligosecretory MM serum free light chain \> 10mg/dL and abnormal kap-pa/lambda free light chain ratio)
• Cytogenetics/FISH confirming t(11;14)
• Prior treatment requirements:
• Prior treatment requirements:
• a. Subjects must have received at least 1 prior treatment line (induction, high-dose, consolidation and maintenance is considered as one treatment line). All patients have to have received at least one proteasome inhibitor and at least one immunomodulatory agent and at least one anti-CD38 monoclonal antibody.
• b. Subjects must have documented evidence of progressive disease on or after the last treatment line.
• c. Subjects with a history of autologous SCT are eligible for study participation provided the following eligibility criteria are met: i. ASCT was \>100 days prior to initiating study treatment, and ii. No active bacterial, viral, or fungal in-fection(s) present.
• Subjects must have adequate organ function, defined as follows:
• a. Hemoglobin ≥8.0 g/dL (without transfusion of red blood cells for the past 14 days) b. Absolute neutrophil count ≥ 1.5 x109/L (with-out growth factor support for the past 14 days) c. Platelet count more or equal 75 x109/L (with-out growth factor or platelet stimulating agents for the past 14 days) d. Adequate hepatic function per local laborato-ry reference range as follows: i. Aspartate aminotransferase (AST) ≤ 2,5 x upper limit of normal (ULN); ii. Alanine aminotransferase (ALT) ≤ 2.5 x ULN iii. Total bilirubin ≤ 1.5 x ULN, except in subjects with congenital bilirubinemia, such as Gilbert syndrome (direct bili-rubin ≤ 1.5 x ULN). Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%.
• e. Subjects must have adequate renal function as demonstrated by eGFR ≥30 mL/min/ 1.73 m2 as calculated by Modified Diet in Renal Disease (MDRD) formula f. Spot urine (albumin/creatinine ratios (spot urine) \<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) g. Corrected serum calcium ≤ 14 mg/dL (≤3,5 mmol/L); or free ionized calcium ˂ 6,5 mg/dL (˂1,6 mmol/L)
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

You may not qualify if:

• Subject has received prior Venetoclax and/or anti BCMA treatment.
• Participant has used an investigational drug or approved systemic anti-myeloma therapy with-in 14 days or five half-lives, whichever is short-er, preceding the first dose of study drug. The only exception is emergency use of a short course of corticosteroids (equivalent of Dexa-methasone 40 mg/day for a maximum of 4 days) up to 7 days before treatment.
• Participant has had plasmapheresis or radia-tion therapy within 7 days prior to first dose of study treatment
• Participant has current corneal epithelial dis-ease except mild changes in corneal epitheli-um
• Participant has current unstable liver or biliary disease
• Participant has a presence of active renal con-dition (infection, requirement for dialysis or any other condition that could affect participant's safety).
• Participant has had major surgery ≤ 4 weeks prior to initiating study treatment. Kyphoplasty is not considered a major surgery.
• Participant must not use contact lenses while participating in this study. Bandage contacts may be prescribed by an eye care professional if needed.
• Participant has any evidence of active mucosal or internal bleeding or other gastrointestinal disease that may significantly alter the absorp-tion of oral drugs.
• Participant has evidence of cardiovascular risk as defined in the protocol
• Participant has known immediate or delayed hypersensitivity reaction or idiosyncratic reac-tions to IMPs or drugs chemically related to IMPs, or any of the components of the study treatment
• Adequately treated in situ carcinoma of the cervix uteri or the breast;
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
• Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment;
• Previous malignancy with no current evi-dence of disease, and which was confined and surgically resected (or treated with other mo-dalities) with curative intent and unlikely to im-pact survival during the duration of the study.

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (5)

University Medical Center Hamburg-Eppendorf

Hamburg, Ham, 20246, Germany

RECRUITING

Klinikum Chemnitz

Chemnitz, Germany

RECRUITING

Uniklinik Heidelberg

Heidelberg, Germany

RECRUITING

UKSH Lübeck

Lübeck, Germany

RECRUITING

Uniklinkum Ulm

Ulm, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma

Interventions

belantamab mafodotin; venetoclax

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Katja Weisel

  Universitätsklinikum Hamburg-Eppendorf

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katja Weisel

CONTACT

+4940741051410; k.weisel@uke.de

Lisa Leypoldt

CONTACT

l.leypoldt@uke.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I: 3+3 Fibonacci design Phase II: single group

Study Record Dates

• First Submitted: April 22, 2023
• First Posted: May 11, 2023
• Study Start: June 28, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)