This phase II trial tests how well tafasitamab, lenalidomide and venetoclax work in treating patients with mantle cell lymphoma that has come back (after a period of improvement) (relapsed) or that has not responded to previous treatment (refractory). Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Lenalidomide is in a class of medications called immunomodulatory agents. It works by helping the immune system kill cancer cells. 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. Giving tafasitamab, lenalidomide and venetoclax together may kill cancer cells more efficiently in patients with relapsed or refractory mantle cell lymphoma.
PRIMARY OBJECTIVE: I. To evaluate the overall response rate in patients with relapsed/refractory mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination. SECONDARY OBJECTIVES: I. To estimate the complete response rate in patients with relapsed/refractory mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination. II. To estimate the duration of response (DoR) in patients with relapsed/refractory mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination. III. To estimate the progression free survival (PFS) in patients with relapsed/refractory mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination. IV. To estimate the overall survival (OS) in patients with relapsed/refractory mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination. V. To evaluate the safety profile of tafasitamab, lenalidomide and venetoclax combination in patients with relapsed/refractory mantle cell lymphoma. CORRELATIVE OBJECTIVES: I. To assess the rate of undetectable minimal residual disease (uMRD) in peripheral blood by multi-color flow cytometry. II. To assess the correlation between MRD status with clinical outcomes such as DoR, PFS and OS. OUTLINE: Patients receive tafasitamab intravenously (IV), lenalidomide orally (PO) and venetoclax PO while on study. Patients may undergo lumbar puncture during screening. Patients undergo computed tomography (CT) scan and blood sample collection and may undergo magnetic resonance imaging (MRI) and tumor biopsy on study and during follow-up. Patients undergo positron emission tomography (PET)/CT, bone marrow biopsy, and bone marrow aspirate throughout the study. After treatment completion, patients follow up every 3 months for 1 year, every 4 months for 1 year and then every 6 months until up to 5 years after entering the trial.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Undergo biopsy
Undergo blood sample collection
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT scan
Given PO
Undergo lumbar puncture
Undergo MRI
Undergo PET/CT scan
Given IV
Given PO
Mayo Clinic in Rochester
Rochester, Minnesota, United States
RECRUITINGM D Anderson Cancer Center
Houston, Texas, United States
NOT_YET_RECRUITINGObjective response rate
A response is defined to be either a partial metabolic response (PMR) or complete metabolic response (CMR) by positron emission tomography (PET) or a partial response (PR) or complete response (CR) by computed tomography (CT) noted as the objective status using Lugano criteria. Objective response rate is defined as the proportion of evaluable patients who achieve response while on treatment. Estimate and corresponding 95% confidence intervals will be calculated according to the approach of Duffy and Santner.
Time frame: Up to 5 years
Complete response rate
Will be estimated for each cohort by the total number of patients who achieve a CMR (by PET/CT) or CR (by CT) at any time on treatment divided by the total number of evaluable patients. Point estimate for complete response rate and corresponding 95% confidence interval will be provided using exact method.
Time frame: Up to 5 years
Duration of response
Will be estimated using the method of Kaplan-Meier separately for each cohort.
Time frame: From first documentation of objective status(PMR or CMR by PET/CT, or PR or CR by CT) to the earliest date of progression or death, assessed up to 5 years
Progression free survival
Will be estimated using method of Kaplan-Meier separately for each cohort.
Time frame: From registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years
Overall survival
Will be estimated using method of Kaplan-Meier for each cohort.
Time frame: From registration to death due to any cause, assessed up to 5 years
Incidence of adverse events (AE)
The maximum grade for each type of AE from each patient will be used for analysis, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration. Adverse events will be reported separately for each cohort.
Time frame: Up to 5 years
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