MC210808 Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) for the Treatment of Multiple Myeloma
Phase I Clinical Trial of Bcl2 Inhibitor Venetoclax in Combination With Lenalidomide and Dexamethasone (Ven-Rd), Daratumumab and Dexamethasone (Ven-Dd), or Daratumumab-Lenalidomide-Dexamethasone (Ven-DRd) in t(11;14) Multiple Myeloma
3 other identifiers
interventional
100
1 country
1
Brief Summary
This phase I trial tests the safety, side effects, and best dose of venetoclax in combination with lenalidomide and dexamethasone, daratumumab and dexamethasone, or daratumumab, lenalidomide, and dexamethasone in treating patients with multiple myeloma. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Lenalidomide is a drug that is similar to thalidomide, and is used to treat multiple myeloma and certain types of anemia. Lenalidomide belongs to the family of drugs called angiogenesis inhibitors. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells, including myeloma cells. Daratumumab may block CD38 and help the immune system kill cancer cells. Adding venetoclax to the other drug combinations may allow control of the cancer than is possible with the current treatments.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 multiple-myeloma
Started Mar 2024
Typical duration for phase_1 multiple-myeloma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 12, 2023
CompletedFirst Posted
Study publicly available on registry
September 18, 2023
CompletedStudy Start
First participant enrolled
March 4, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2028
December 24, 2025
December 1, 2025
4.7 years
September 12, 2023
December 18, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Dose-limiting toxicity
Dose-limiting toxicities (DLT) are defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
28 Days (1 treatment cycle); Up to 3 years
Secondary Outcomes (2)
Frequency and severity of treatment-emergent adverse events
Up to 30 days after completion of study treatment
Best response while on treatment
Up to 3 years
Study Arms (3)
Arm A (Ven-Dd)
EXPERIMENTALPatients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.
Arm B (Ven-Rd)
EXPERIMENTALPatients receive venetoclax PO QD on days 1-28 of each cycle, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, and during follow-up.
Arm C (Ven-DRd)
EXPERIMENTALPatients receive venetoclax PO QD on days 1-28 of each cycle, daratumumab SC on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, lenalidomide PO QD on days 1-21 of each cycle, and dexamethasone PO on days 1, 8, 15, and 22 of cycles 1-12. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo chest x-ray and optional collection of blood samples during screening. In addition, patients undergo x-rays, WBLDCT, PET/CT or MRI scans during screening and on study, and bone marrow aspiration and biopsy during screening, on study, and during follow-up.
Interventions
Undergo optional collection of blood samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo chest x-ray
Undergo PET/CT
Given SC
Given PO
Given PO
Undergo WBLDCT
Undergo MRI
Undergo PET/CT
Given PO
Undergo x-rays
Eligibility Criteria
You may qualify if:
- PRE-REGISTRATION: Diagnosis of active MM with bone marrow plasma cell fluorescence in situ hybridization (FISH) test run under an Investigational Device Exemption (IDE) demonstrating of t(11;14), either from time of diagnosis or confirmed with IDE at Mayo Clinic after time of diagnosis, during screening period for study. Note: Samples tested beyond 72 hours from the collection will not be considered adequate for trial enrollment
- PRE-REGISTRATION: Group 1 - At least one prior line of therapy which did not include venetoclax
- PRE-REGISTRATION: Group 2 - No more than 1 cycle of any commonly used myeloma regimen for treatment of newly diagnosed MM
- PRE-REGISTRATION: Patient is not being considered for stem cell transplant (group 2, newly diagnosed only)
- REGISTRATION: Age ≥ 18 years
- REGISTRATION: Calculated creatinine clearance (using Cockcroft-Gault equation) ≥ 30 mL/min (obtained ≤ 14 days prior to registration)
- REGISTRATION: Absolute neutrophil count (ANC) ≥ 1000/uL (without growth factor support) (obtained ≤ 14 days prior to registration)
- REGISTRATION: Un-transfused Platelet count ≥ 75000/uL (≥ 50,000/uL if marrow plasma cells \[PC\]% \> 50%) (obtained ≤ 14 days prior to registration)
- REGISTRATION: Hemoglobin ≥ 8.0 g/dL (transfusion permitted) (obtained ≤ 14 days prior to registration)
- REGISTRATION: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (known Gilbert's syndrome are allowed provided bilirubin ≤ 2.5 mg/dL) (obtained ≤ 14 days prior to registration)
- REGISTRATION: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (obtained ≤ 14 days prior to registration)
- REGISTRATION: Alkaline phosphatase ≤ 750 U/L (obtained ≤ 14 days prior to registration)
- REGISTRATION: Measurable disease of multiple myeloma as defined by at least ONE of the following:
- Serum monoclonal protein ≥ 1.0 g/dL
- ≥ 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- +21 more criteria
You may not qualify if:
- PRE-REGISTRATION: History of any active malignancy within the past 2 years prior to screening, with the exception of:
- Adequately treated carcinoma in situ of the uterine cervix
- Adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin
- Asymptomatic prostate cancer with no requirement for therapy
- Previous malignancy surgically resected (or treated with other modalities) with curative intent
- REGISTRATION: Other concurrent chemotherapy or any ancillary therapy considered investigational
- Note: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment
- REGISTRATION: Major surgery ≤ 14 days prior to study registration
- REGISTRATION: History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- REGISTRATION: Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- REGISTRATION: Administration of strong/moderate CYP3A inhibitors or inducers ≤ 28 days prior to registration
- REGISTRATION: Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
- REGISTRATION: Participation in other clinical trials, including those with other investigational agents not included in this trial, ≤ 30 days prior to registration
- REGISTRATION: Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of venetoclax including difficulty swallowing REGISTRATION: Heart failure \> New York Heart Association (NYHA) class II
- REGISTRATION: Presence of positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Mayo Cliniclead
Study Sites (1)
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Shaji K. Kumar, MD
Mayo Clinic in Rochester
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 12, 2023
First Posted
September 18, 2023
Study Start
March 4, 2024
Primary Completion (Estimated)
December 1, 2028
Study Completion (Estimated)
December 1, 2028
Last Updated
December 24, 2025
Record last verified: 2025-12