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

Phase 1

Recruiting

• Conditions: Multiple Myeloma in Relapse; Multiple Myeloma
• Interventions: Drug: Belantamab mafodotin, Venetoclax

• Registration Number: NCT05853965
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

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)

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-22
• Study First Submitted QC: 2023-05-10
• Study First Posted: 2023-05-11
• Study Start: 2023-06-28
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-17
• Last Update Posted: 2023-07-19
• Primary Completion: 2026-11
• Study Completion: 2026-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

Not provided

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Exclusion Criteria

1. Subject has received prior Venetoclax and/or anti BCMA treatment.

2. 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.

3. Participant has had plasmapheresis or radia-tion therapy within 7 days prior to first dose of study treatment

4. Participant has current corneal epithelial dis-ease except mild changes in corneal epitheli-um

5. Participant has current unstable liver or biliary disease

6. Participant has a presence of active renal con-dition (infection, requirement for dialysis or any other condition that could affect participant's safety).

7. Participant has had major surgery ≤ 4 weeks prior to initiating study treatment. Kyphoplasty is not considered a major surgery.

8. Participant must not use contact lenses while participating in this study. Bandage contacts may be prescribed by an eye care professional if needed.

9. Participant has any evidence of active mucosal or internal bleeding or other gastrointestinal disease that may significantly alter the absorp-tion of oral drugs.

10. Participant has evidence of cardiovascular risk as defined in the protocol

11. 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

12. Participant has an invasive malignancy other than disease under study within 5 years before trial inclusion, except

    • 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.

13. Participant is pregnant or lactating

14. Participants who have had prior allogeneic stem cell transplant.

15. Participants with symptomatic amyloidosis, ac-tive POEMS syndrome (polyneuropathy, or-ganomegaly, endocrinopathy, monoclonal plasmaproliferative disorder, skin changes) or active plasma cell leukaemia at the time of screening.

16. Participants with any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions (including lab abnormalities) that could interfere with participant's safety, ob-taining informed consent or compliance to the study procedures.

17. Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B sur-face antigen (HBsAg) or antibodies to hepatitis B surface and core antigen (anti HBs and anti HBc respectively), or hepatitis C (anti-HCV an-tibody positive or HCV RNA quantitation posi-tive).

18. Current immune or inflammatory conditions re-quiring immunosuppressive treatment (e.g. systemic lupus erythematosus, rheumatoid ar-thritis).

19. Subject must not have received any live vac-cines within 8 weeks prior to first dose of study treatment.

20. Subject must not use or anticipate the use of prohibited medications or foods during study participation.

21. Subject does not have a history of or show any signs of known meningeal/central nervous sys-tem involvement by myeloma.

22. Evidence of other clinically significant uncon-trolled condition(s) that is likely to interfere with the study proce-dures or results, or that in the opinion of the investigator, would constitute a hazard for the participation in this study.

23. Subject is known or suspected of not being able to comply with the study protocol. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit or confound the pro-tocol-specified assessments.

24. Treatment with any of the following within 7 days prior to the first dose of study drug:

    1. moderate or strong cytochrome P450 3A (CYP3A) inhibitors
    2. moderate or strong CYP3A inducers

25. Administration or consumption of any of the fol-lowing within 3 days prior to the first dose of study drug:

    1. grapefruit or grapefruit products
    2. Seville oranges (including marmalade con-taining Seville oranges)
    3. star fruit

26. Participation in any other clinical trial (with the exclusion of observational studies)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Belantamab mafodotin, Venetoclax	Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 800mg QD
Cohort 3	Belantamab mafodotin, Venetoclax	Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 400mg QD Dexamethasone 40mg Q1W (20mg for subjects ≥ 75 years)
Cohort 1	Belantamab mafodotin, Venetoclax	Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 400mg QD
Cohort 4	Belantamab mafodotin, Venetoclax	Belantamab Mafodotin 1.9 mg/kg Q6W Venetoclax 800mg QD Dexamethasone 40mg Q1W (20mg for subjects ≥ 75 years)

Primary Outcome Measures

Name	Time	Method
Recommended Phase II dose (RP2D)	approx. 9 months	Establishment of Recommended Phase II dose (RP2D), Evaluation of safety profile, including maximum tolerated dose

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	through study completion, an average of 2 years	Overall Response Rate
Minimal residual disease (MRD) negativity	through study completion, an average of 2 years	Minimal residual disease (MRD) negativity rate and duration
Progression free survival (PFS)	through study completion, an average of 2 years	Progression free survival (PFS)
Duration of response (DOR)	through study completion, an average of 2 years	Duration of response (DOR)

Trial Locations

Locations (1)

University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Ham, Germany