Venetoclax and Rituximab for the Initial Treatment of Older Patients with Untreated Mantle Cell Lymphoma
This phase II trial tests how well venetoclax and rituximab works in treating older patients with mantle cell lymphoma (MCL) who have not yet received treatment (untreated). 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. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Giving venetoclax and rituximab may shrink or make the cancer cells disappear in older patients with untreated MCL.
Inclusion Criteria
- Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma as defined by the World Health Organization (WHO) classification scheme
- Age ≥ 60
- Subjects must be previously untreated for mantle cell lymphoma and deemed to require treatment by the treating physician
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
- Absolute neutrophil count (ANC) ≥ 1000/uL (without growth factor support) * These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias
- Platelets ≥ 75,000/mm^3 (entry platelet count must be independent of transfusion within 14 days of screening) (without growth factor support) * These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias
- Hemoglobin ≥ 9.0 g/dL (without growth factor support) * These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias
- Calculated creatinine clearance ≥ 40 mL/min; determined via the Cockcroft-Gault formula
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x upper limit of normal (ULN)
- Bilirubin ≤ 1.5 x ULN. Subjects with Gilbert's syndrome may have a bilirubin > 1.5 x ULN * These criteria may be waived by study investigators if abnormal values believed to be due to lymphoma
- Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test performed as follows: * At screening on a serum sample obtained within 14 days prior to the first study drug administration, and * Prior to dosing on a urine sample obtained on cycle 1 day 1 if it has been > 7 days since obtaining the serum pregnancy test results
- All female subjects not surgically sterile or postmenopausal (for at least 1 year) and nonvasectomized male subjects must practice at least 1 of the following methods of birth control: * Total abstinence from sexual intercourse (minimum 1 complete menstrual cycle) * A vasectomized partner(s) * Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) for at least 3 months prior to study drug administration * Double-barrier method (condoms and diaphragm with spermicidal [sponge, jellies or creams])
- Ability to understand and willingness to sign institutional review board (IRB)-approved informed consent
Exclusion Criteria
- Subject has blastoid-variant mantle cell lymphoma
- Subject requires immediate cytoreduction as determined by study investigators
- Subject has documented central nervous system (CNS) involvement of mantle cell lymphoma
- Subject has Ann Arbor stage I or contiguous stage II mantle cell lymphoma
- Subject has an uncontrolled infection
- Subject has HIV infection
- All subjects will be screened for hepatitis B (hepatitis B surface antigen [HBsAg], anti-hepatitis B surface antibody [HBs], anti-hepatitis B core antibody [HBc] immunoglobulin M [IgM] and total) and hepatitis C (antibody or ribonucleic acid [RNA]). Subjects who are positive for hepatitis B by HBsAg or deoxyribonucleic acid (DNA) as well as subjects positive for hepatitis C will be excluded. Subjects with anti-HBc positivity and DNA negative may be included but will be required to undergo monthly hepatitis B virus (HBV) DNA testing and liver function liver function testing (AST, ALT, alkaline phosphatase, total bilirubin). Patients with hepatitis C virus (HCV) antibody positivity and HCV polymerase chain reaction (PCR) negativity are eligible to be included
- Subject requires the use of warfarin
- Subject has received immunization with live virus vaccine within 28 days prior to the first dose of study drug
- A female subject is pregnant or breast-feeding
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05025423.
Locations matching your search criteria
United States
Maryland
Baltimore
PRIMARY OBJECTIVE:
I. To estimate the overall response rate (ORR) after four cycles of venetoclax and rituximab. The ORR will be the sum of complete (CR) and partial responses (PR).
SECONDARY OBJECTIVES:
I. To estimate the proportions of CR, PR, stable disease, and disease progression after four cycles.
II. To evaluate the rate of CR and PR after 8 cycles of venetoclax and rituximab.
III. To evaluate the progression free survival (PFS) and overall survival (OS) in the intent to treat (ITT) population.
IV. To evaluate the duration of response (DOR) for participants achieving a CR or PR.
V. To evaluate the toxicities in patients receiving venetoclax and rituximab.
EXPLORATORY OBJECTIVE:
I. To evaluate for mutations in TP53 and correlate with CR, PR, and duration of response.
OUTLINE:
Patients receive rituximab intravenously (IV) on day 1 of each cycle and venetoclax orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
CR AFTER 4 CYCLES: Patients with a CR continue venetoclax and rituximab for an additional 4 cycles. After restaging, patients with a CR continue to receive venetoclax and rituximab for an additional 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive rituximab IV on day 1. Treatment repeats every 2 months for up to 3 years for a total of 18 doses.
PR AFTER 4 CYCLES: Patients continue venetoclax and rituximab for an additional 4 cycles. After restaging, patients with a CR continue to receive venetoclax and rituximab for an additional 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive rituximab IV on day 1. Treatment repeats every 2 months for up to 3 years for a total of 18 doses. After restaging, patients with a PR receive rituximab IV on day 1, venetoclax PO QD on days 1-10 and bendamustine IV over 30 minutes on days 1 and 2 of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
PROGRESSION OR STABLE DISEASE AFTER 4 CYCLES: Patients are removed from study to receive standard of care therapy.
Patients also undergo bone marrow biopsy and positron emission tomography (PET)/computed tomography (CT) or magnetic resonance imaging (MRI) at screening, at cycle 5 day 1 and cycle 9 day 1. Additionally patients undergo blood sample collection and CT throughout the study.
After completion of study treatment, patients are followed up every 12 weeks for up to 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorLode J. Swinnen
- Primary IDJ2146
- Secondary IDsNCI-2024-09879, IRB00288478
- ClinicalTrials.gov IDNCT05025423