Overview

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

Status:
Recruiting
Trial end date:
2028-12-01
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Mayo Clinic
Treatments:
Antibodies, Monoclonal
BB 1101
Daratumumab
Dexamethasone
Dexamethasone acetate
Ichthammol
Lenalidomide
Venetoclax
Criteria
Inclusion Criteria:

- Diagnosis of active MM with bone marrow plasma cell fluorescence in situ hybridization
(FISH) test demonstrating presence of t(11;14) at the time of diagnostic bone marrow
biopsy specimen at Mayo Clinic. NOTE: Testing for t(11;14) will be performed using
specific FISH test under an Investigational Device Exemption (IDE). Samples tested
beyond 72 hours from the collection will not be considered adequate for trial
enrollment

- Group 1 - At least once prior line of therapy which did not include venetoclax

- Group 2 - No more than 1 cycle of any commonly used myeloma regimen for treatment of
newly diagnosed MM

- Patient is not being considered for stem cell transplant (group 2, newly diagnosed
only)

- Age ≥ 18 years

- Calculated creatinine clearance (using Cockcroft-Gault equation) ≥ 30 mL/min (obtained
≤ 14 days prior to registration)

- Absolute neutrophil count (ANC) ≥ 1000/uL (without growth factor support) (obtained ≤
14 days prior to registration)

- Un-transfused Platelet count ≥ 75000/uL (≥ 50,000/uL if marrow plasma cells [PC]% >
50%) (obtained ≤ 14 days prior to registration)

- Hemoglobin ≥ 8.0 g/dL (transfusion permitted) (obtained ≤ 14 days prior to
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)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN
(obtained ≤ 14 days prior to registration)

- Alkaline phosphatase ≤ 750 U/L (obtained ≤ 14 days prior to 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

- Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum
immunoglobulin kappa to lambda free light chain ratio

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

- Provide written informed consent

- Ability to complete questionnaire(s) by themselves or with assistance

- Negative serum pregnancy test done ≤ 7 days prior to registration, for women of
childbearing potential only

- Willing to follow strict birth control measures as suggested by the study

- Female participant is eligible to participate if she is not pregnant or breastfeeding,
and at least one of the following conditions applies:

- Is not a woman of childbearing potential (WOCBP) OR

- Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal
toxicity and prescribed under a pregnancy prevention/controlled distribution
program, WOCBP participants will be eligible if they commit to either:

- Abstain continuously from heterosexual sexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis) and
agree to remain abstinent OR

- To use birth control as follows:

- Two methods of reliable birth control (one method that is highly
effective and one additional effective (barrier) method), beginning 4
weeks prior to initiating treatment with lenalidomide, during therapy,
during dose interruptions and continuing for 4 weeks following
discontinuation of lenalidomide treatment

- Male participants are eligible to participate if they agree to the following from the
time of first dose of study treatment until 28-days after the last dose of
lenalidomide, to allow for clearance of any altered sperm:

- Refrain from donating sperm PLUS either:

- Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle (abstinent on a long term and persistent basis) and agree to
remain abstinent OR

- Must agree to use contraception/barrier as detailed below:

- Agree to use a male condom, even if they have undergone a successful
vasectomy, and female partner to use an additional highly effective
contraceptive method with a failure rate of < 1% per year as when
having sexual intercourse with a woman of childbearing potential
(including pregnant females)

- Life expectancy ≥ 12 weeks

- Willing to return to enrolling institution for follow-up (during the Active Monitoring
Phase of the study)

- Willing to provide research bone marrow aspirate specimen

- Willing to follow the requirements of the Revlimid (Registered Trademark) Risk
Evaluation and Mitigation Strategy (REMS) program

Exclusion Criteria:

- 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

- 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

- Major surgery ≤ 14 days prior to study 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

- Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

- Administration of strong/moderate CYP3A inhibitors or inducers ≤ 14 days OR 5
half-lives prior to registration, whichever is longer

- Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent

- Participation in other clinical trials, including those with other investigational
agents not included in this trial, ≤ 30 days prior to registration

- Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of venetoclax including difficulty swallowing

- Heart failure > New York Heart Association (NYHA) class II

- 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

- 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

- Note: Hepatitis RNA testing is optional and participants with negative hepatitis
C antibody test are not required to also undergo hepatitis C RNA testing