Clinical Trials /

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

NCT03219047

Description:

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.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Patient-Derived Xenografts in Personalizing Treatment for Patients With Relapsed/Refractory Mantle Cell Lymphoma
  • Official Title: A Pilot Study Evaluating Xenografts to Personalize Therapies (PDX) in Relapsed Mantle Cell Lymphoma to Optimize Response: The EXPLORE Trial

Clinical Trial IDs

  • ORG STUDY ID: 2017-0051
  • SECONDARY ID: NCI-2018-01117
  • SECONDARY ID: 2017-0051
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT03219047

Conditions

  • Recurrent Mantle Cell Lymphoma
  • Refractory Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765Cohort 2 (Co-trial cohort)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 2 (Co-trial cohort)ExperimentalPatients 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.
  • Ibrutinib
Cohort I (Traditional cohort)ExperimentalPatients 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.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Confirmed MCL tissue diagnosis.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Patients must have
                 relapsed/progressed after any therapy for MCL.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Understand and voluntarily sign an
                 Institutional Review Board (IRB)-approved informed consent form.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Patients must be willing to allow
                 residual tissue to be collected for both in vitro, in vivo (PDX) testing and molecular
                 profiling.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Patients must have bi-dimensional
                 measurable disease as per Lugano criteria (bone marrow or gastrointestinal [GI] only
                 involvement is acceptable).
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Eastern Cooperative Oncology Group
                 (ECOG) performance status of 0-2.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Disease free of other prior
                 malignancies of >= 3 years with exception of currently treated basal cell, squamous
                 cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other
                 malignancies in remission (including prostate cancer patients in remission from
                 radiation therapy, surgery or brachytherapy) or not actively being treated, with a
                 life expectancy > 2 years.
    
              -  FOR TISSUE COLLECTION TO ESTABLISH PDX (PART 1): Reasonable expectation that the
                 patient can wait 3-6 months for generation of PDX data for subsequent treatment
                 selection.
    
              -  FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH
                 STANDARD OF CARE (PART 2): The patient PDXs must have generated informative mouse
                 xenograft data during Part 1 to participate in Part 2.
    
              -  FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH
                 STANDARD OF CARE (PART 2): The patient condition remains suitable for the selected
                 therapy. If the patient receives prior therapy with a given agent (X) and progressed,
                 but the testing in Part 1 found this agent to be effective in a combination, the
                 patient remains eligible for this combination that includes agent X.
    
              -  FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH
                 STANDARD OF CARE (PART 2): Patients should ideally have bi-dimensional measurable
                 disease (leukemia phase only, bone marrow only, splenomegaly only, or GI involvement
                 only is acceptable).
    
              -  FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH
                 STANDARD OF CARE (PART 2): 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.
    
              -  FOR PDX-GUIDED THERAPY THROUGH ONGOING TRIALS AT MD ANDERSON OR OFF-PROTOCOL WITH
                 STANDARD OF CARE (PART 2): Patients must have adequate organ function for drugs(s) or
                 combination being utilized (dependent on the drug[s] being given).
    
            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.
    
              -  Pregnant or breastfeeding females.
    
              -  Known human immunodeficiency virus (HIV) infection. Patients with 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 of
                 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 IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: PDX
                 data are non-informative.
    
              -  THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR:
                 Tumors do not engraft in the mice or do not respond to any of the selected agents.
    
              -  THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: In
                 Cohort 2, if disease progression occurs before Part 1 data are available, then they
                 will be transferred to Cohort 1.
    
              -  THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Part
                 1 data contradict clinical judgment. The investigator should discuss with the
                 principal investigator (PI) and use the best discretion.
    
              -  THE PATIENT IS INELIGIBLE TO PARTICIPATE IN PART 2 IF ANY OF THE FOLLOWING OCCUR: Any
                 other exclusion criteria set forth by individual treatment protocol of the active
                 clinical trial(s) through which patients are going to be treated.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Feasibility defined as available patient-derived xenograft (PDX) results before relapse
    Time Frame:Up to 1 year
    Safety Issue:
    Description: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.

    Secondary Outcome Measures

    Measure:Objective response (OR) rate (complete + partial responses)
    Time Frame:Up to 1 year
    Safety Issue:
    Description: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.
    Measure:Incidence of adverse events
    Time Frame:Up to 1 year
    Safety Issue:
    Description: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.
    Measure:Progression-free survival (PFS)
    Time Frame:Up to 1 year
    Safety Issue:
    Description:The distribution of PFS will be estimated using the method of Kaplan and Meier. Cox proportional hazard regression will be employed for multivariate analysis.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:M.D. Anderson Cancer Center

    Last Updated

    May 20, 2019