This early phase I pilot trial studies how well patient-derived xenografts work in personalizing treatment for patients with mantle cell lymphoma that has come back (relapsed) or that isn't responding to treatment (refractory). Xenograft models involve taking a piece of tissue from a tumor that was previously collected and putting that tissue inside of a mouse in the laboratory. This allows the tumor to grow in the mouse so that researchers can test the effects of certain drugs. If the drugs have an effect on the tumor(s) in the mice, patients may receive that treatment for mantle cell lymphoma.
PRIMARY OBJECTIVES: I. To determine the feasibility in the patients treated with the patient-derived xenografts (PDX)-directed therapies in both cohorts (cohort 1 and cohort 2). II. To establish mouse xenografts from the mantle cell lymphoma (MCL) tissue samples of patients with relapsed MCL. III. To determine the activity of a panel of anticancer drugs consistent with the patient's clinical history against these MCL cells in vitro. IV. To test the best selected in vitro options in the PDX model to create a profile, in rank order based on the efficacy of best 3-5 options, of individualized patient treatment options. V. To determine the feasibility of predicting the patient's response to therapy using a PDX-based strategy. VI. To define susceptibility and resistance determinants to the drugs in xenografted tumors. SECONDARY OBJECTIVES: I. To determine the objective response (OR) rate (complete + partial responses). II. To determine safety and toxicity. III. To determine progression-free survival (PFS). EXPLORATORY OBJECTIVES: I. To correlate detected gene mutations and changes in ribonucleic acid (RNA) and/or protein expression with treatment responses. OUTLINE: patients are assigned to 1 of 2 cohorts. COHORT 1 (TRADITIONAL COHORT): Patients who have previously received ibrutinib, acalabrutinib, PI3K inhibitor ACP-319, or BTK inhibitor BGB-3111 receive treatment through ongoing clinical trials at MD Anderson or standard of care. At the same time, previously collected tissue is used to develop PDX models and suitable drugs/regimens are tested in the PDX models. Patients then receive treatment based on the results of the PDX models through another clinical trial or standard of care. COHORT 2 (CO-TRIAL COHORT): Patients receive ibrutinib at standard dose and schedule through an ongoing MD Anderson clinical trial. Patients that respond to ibrutinib but experience relapse or disease progression receive treatment based on the results of the PDX models as in Cohort 1 if they are available. Patients who experience relapse after treatment with ibrutinib are moved to Cohort I if the PDX models are not ready.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Receive standard of care
Given at standard dose and schedule
Xenograft developed
Receive treatment based on the results of the PDX models
M D Anderson Cancer Center
Houston, Texas, United States
Feasibility defined as available patient-derived xenograft (PDX) results before relapse
This will be established if both PDX model is built successfully based on the primary tumor samples, and the results of the PDX results are available before disease relapse. We consider the study feasible if the posterior probability of feasibility rate above 30% is larger than 80% at the end of the study. The feasibility rate in each cohort will be summarized by frequency and 95% posterior credible interval.
Time frame: Up to 1 year
Objective response (OR) rate (complete + partial responses)
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate. Will be estimated by a Bayesian posterior credible interval, and summarized by frequency and 95% posterior credible interval.
Time frame: Up to 1 year
Incidence of adverse events
Toxicity data by type and severity will be summarized by frequency tables. Will be estimated by a Bayesian posterior credible interval, and summarized by frequency and 95% posterior credible interval.
Time frame: Up to 1 year
Progression-free survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan and Meier. Cox proportional hazard regression will be employed for multivariate analysis.
Time frame: Up to 1 year
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