NCT03219047

Patient-Derived Xenografts in Personalizing Treatment for Patients With Relapsed/Refractory Mantle Cell Lymphoma

A Pilot Study Evaluating Xenografts to Personalize Therapies (PDX) in Relapsed Mantle Cell Lymphoma to Optimize Response: The EXPLORE Trial

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 1 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Recurrent Mantle Cell Lymphoma
• Refractory Mantle Cell Lymphoma

Interventions

Type	Name	Description
OTHER	Best Practice	Receive standard of care
DRUG	Ibrutinib	Given at standard dose and schedule
OTHER	Patient Derived Xenograft	Xenograft developed
OTHER	Personalized Medicine	Receive treatment based on the results of the PDX models

Timeline

• Start date: 2018-12-20
• Primary completion: 2023-07-03
• Completion: 2023-07-03
• First posted: 2017-07-17
• Last updated: 2023-07-27

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study