Interrogating Biological Signaling Pathway Dysregulations and In Vitro Screening With Personalized Therapies in Relapsed or Refractory Mantle Cell Lymphoma, MCL MATCH Trial

Overview

This clinical trial collects and tests samples using genetic testing to find personalized treatments that may work best for patients with mantle cell lymphoma (MCL) that has come back (relapsed) or does not respond to treatment (refractory). Several types of MCL are difficult to treat due to specific genetic changes (mutations or alterations in the DNA/RNA expression in the cells) that make them not respond to a certain type of drug called a Bruton's tyrosine kinase (BTK) inhibitor. The goal of this clinical research study is to use genetic testing to identify which drugs may be most effective in treating patients with MCL who have this type of genetic mutation.

Full Title of Study: “A Pilot Study of Interrogating Biological Signaling Pathway Dysregulations and In Vitro Screening With Personalized Therapies in Resistant Mantle Cell Lymphoma (MCL) – the MCL MATCH Trial”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Screening
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 31, 2022

Detailed Description

PRIMARY OBJECTIVE: I. To evaluate the feasibility of the proposed therapy based on dysregulated cell signaling pathways in combination with in vitro drug activity. SECONDARY OBJECTIVES: I. Overall response rates (complete response [CR] + partial response [PR]). II. Safety in patients who were treated with matched personalized therapies. III. Duration of response. IV. Progression free survival (PFS). V. Overall survival (OS). EXPLORATORY OBJECTIVE: I. Correlation of somatic mutations in MCL with cell signaling dysregulated activity and therapeutic implications of somatic mutations in relapsed MCL. OUTLINE: Patients undergo blood, saliva or tissue sample collection for messenger ribonucleic acid analysis (mRNA) analysis and drug efficacy testing. Patients assigned treatment per the results are followed every 1 cycle of therapy for 1 year, every 2 months for 1 year, every 4 months for 1 year then every 6 months thereafter.

Interventions

  • Procedure: Biospecimen Collection
    • Undergo blood, saliva or tissue sample collection
  • Other: Follow-Up
    • Undergo follow-up

Arms, Groups and Cohorts

  • Experimental: Screening (biospecimen collection)
    • Patients undergo blood, saliva or tissue sample collection for mRNA analysis and drug efficacy testing. Patients assigned treatment per the results are followed every 1 cycle of therapy for 1 year, every 2 months for 1 year, every 4 months for 1 year then every 6 months thereafter.

Clinical Trial Outcome Measures

Primary Measures

  • Feasibility rate
    • Time Frame: Up to 1 year
    • Will be reported by frequency with exact 95% confidence interval. Logistic regression will be utilized to assess the effect of patient prognostic factors on the feasibility and response rate.

Secondary Measures

  • Response rate
    • Time Frame: Up to 1 year
    • Will be reported by frequency with exact 95% confidence interval. Logistic regression will be utilized to assess the effect of patient prognostic factors on the feasibility and response rate.
  • Incidence of adverse events
    • Time Frame: Up to 1 year
    • Toxicity data by type and severity will be summarized by frequency tables.
  • Duration of response
    • Time Frame: Up to 1 year
  • Progression free survival
    • Time Frame: Up to 1 year
    • Will be estimated using the method of Kaplan and Meier. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.
  • Overall survival
    • Time Frame: Up to 1 year
    • Will be estimated using the method of Kaplan and Meier. Cox proportional hazard regression will be employed for multivariate analysis on time-to-event outcomes.

Participating in This Clinical Trial

Inclusion Criteria

  • Confirmed MCL tissue diagnosis with CD20- and cyclin D1-positive cells, or cyclin D1 negative but t (11;14) positive and diagnosis confirmed by pathologist from the tissue biopsy – Patients with confirmed relapsed/refractory (R/R) MCL – Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form – Patients must have a biopsy-accessible lesion and be willing to undergo biopsy – Patients must have bi-dimensional measurable disease as per Cheson criteria (bone marrow and or gastrointestinal [GI] only involvement is acceptable) – Age >= 18 years at the time of signing the informed consent – Absolute neutrophil count >= 1.0 x 10^9/L – Absolute lymphocyte count >= 0.6 x 10^9/L – Platelet count >= 50 x 10^9/L – Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 – Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x upper limit of normal (ULN) – Total bilirubin =< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin – Creatinine clearance (CLcr) > 50 mL/min – Cardiac ejection fraction has to be >= 50% by echocardiogram (ECHO) or multigated acquisition (MUGA) – No anticoagulation is allowed. No anti-platelet agents such as aspirin or clopidogrel are allowed – Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test. Men must agree not to father a child and agree to use a condom if his partner is of child-bearing potential Exclusion Criteria:

  • Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form. Examples include but are not limited to uncontrolled hypertension, uncontrolled diabetes mellitus, active /symptomatic coronary artery disease, active infection, active hemorrhage, and psychiatric illness – Patient with rapid progressive disease, which means If the patient has significant pain from tumor, very significant disease related symptoms or if the tumor is more than 5 cm in the longest diameter with symptoms, or if the tumor in obstructing any internal organs, if the tumor is threatening the spinal cord – Pregnant or breastfeeding females – Known human immunodeficiency virus (HIV) infection or active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody). Known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation – The patient has a prior or concurrent malignancy that, in the opinion of the investigator, presents a greater risk to the patient's health and survival than the MCL, with a life expectancy =< 2 years – Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent, or any class 3 (moderate) or 4 (severe) cardiac disease defined by the New York Heart Association classification – Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, major surgery within 4 weeks, or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drug – The patient receives corticosteroids for non-malignant conditions (e.g., asthma, inflammatory bowel disease) equivalent to a dexamethasone dose >= 4 mg/day or prednisone >= 20 mg/day

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • M.D. Anderson Cancer Center
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Luhua (Michael) Wang, Principal Investigator, M.D. Anderson Cancer Center

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