Combination treatment of Belantamab Mafodotin and Venetoclax in treatment of relapsed and refractory t(11;14) Multiple Myeloma (Phase I/IIa) The BELI(E)VE-Trial

Phase 1

• Conditions: relapsed and refractory t(11; 14) Multiple Myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-001413-37-DE
• Lead Sponsor: niversity Medical Center Hamburg-Eppendorf

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2023-01-05
• Last Update Posted: 18 September 2023

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

1. Subjects must be = 18 years of age.
2. Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of = 2
3. Subjects must voluntarily sign and date an informed consent form
4. 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 diagnostic criteria (IMWG updated criteria 2014, Rajkumar et al. 2014) with measurable disease 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 kappa/lambda free light chain ratio)
5. Cytogenetics/FISH confirming t(11;14)
6. Prior treatment requirements:
Phase 1:
a. Subjects must have received at least 4 prior treatments (induction, high-dose, consolidation and maintenance is considered as one treatment line) and are refractory to at least one proteasome inhibitor, at least one immunomodulatory drug and at least one monoclonal anti CD38 antibody.
b. Subjects must have documented evidence of progressive disease during their last treatment.
Phase 2:
c. Subjects must have received at least 1 prior treatment line (induction, high-dose, consolidation and maintenance is considered as one treatment line). All patients must have received at least one proteasome inhibitor and at least one immunomodulatory agent and at least one anti CD38 monoclonal antibody.
d. Subjects must have documented evidence of progressive disease on or after the last treatment line.
Phase 1+2
e. 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 infection(s) present.
7. 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 (without growth factor support for the past 14 days)
c. Platelet count more or equal 75 x109/L (without growth factor or platelet stimulating agents for the past 14 days)
d. Adequate hepatic function per local laboratory 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 bilirubin = 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)
8. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
a. Is not a woman of childbearing potential (WOCBP)
OR
b. Is a WOCBP and using a contraceptive method that is highly effective and agrees not to donate eggs (

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 within 14 days or five half-lives, whichever is shorter, preceding the first dose of study drug. The only exception is emergency use of a short course of corticosteroids (equivalent of Dexamethasone 40 mg/day for a maximum of 4 days) up to 7 days before treatment.
3. Participant has had plasmapheresis or radiation therapy within 7 days prior to first dose of study treatment
4. Participant has current corneal epithelial disease except mild changes in corneal epithelium
5. Participant has current unstable liver or biliary disease defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
6. Participant has a presence of active renal condition.
7. Participant has had major surgery = 4 weeks prior to initiating study treatment.
8. Participant must not use contact lenses while participating in this study.
9. Participant has any evidence of active mucosal or internal bleeding or other gastrointestinal disease that may significantly alter the absorption of oral drugs.
10. Participant has evidence of cardiovascular risk including any of the following:
a. Evidence of current clinically significant uncontrolled arrhythmias, including clinically significant ECG abnormalities such as 2nd degree (Mobitz Type II) or 3rd degree atrioventricular (AV) block
b. History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting or bypass grafting within three (3) months prior to Screening.
c. Class III or IV heart failure as defined by the New York Heart Association functional classification system
d. Uncontrolled hypertension
e. Left ventricular Ejection Fraction = 50%
11. Participant has known immediate or delayed hypersensitivity reaction or idiosyncratic reactions 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 evidence of disease, and which was confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact 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, active POEMS syndrome 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 that could interfere with participant’s safety, obtaining informed consent or compliance to the study procedures.
17. Subject is known to be seropositive for HIV or hepatitis B, or hepatitis C.
18. Current immune or inflammatory conditions requiring immunosuppressive treatment.
19. Subject must not have received any live vaccines within 8 weeks prior to first dose of study treatment.
20. Subject must not use or anticipate the use of prohibited medic

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified