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

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ClinicalTrials.gov Identifier: NCT03219047
Recruitment Status : Recruiting
First Posted : July 17, 2017
Last Update Posted : May 22, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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.

Condition or disease Intervention/treatment Phase
Recurrent Mantle Cell Lymphoma Refractory Mantle Cell Lymphoma Other: Best Practice Drug: Ibrutinib Other: Patient Derived Xenograft Other: Personalized Medicine Early Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Evaluating Xenografts to Personalize Therapies (PDX) in Relapsed Mantle Cell Lymphoma to Optimize Response: The EXPLORE Trial
Actual Study Start Date : December 20, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: 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.
Other: Best Practice
Receive standard of care
Other Names:
  • standard of care
  • standard therapy

Drug: Ibrutinib
Given at standard dose and schedule
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • Imbruvica
  • PCI-32765

Other: Patient Derived Xenograft
Xenograft developed
Other Names:
  • Patient-Derived Xenograft
  • Patient-Derived Xenograft Model
  • PDTX
  • PDX

Other: Personalized Medicine
Receive treatment based on the results of the PDX models

Experimental: Cohort I (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.
Other: Best Practice
Receive standard of care
Other Names:
  • standard of care
  • standard therapy

Other: Patient Derived Xenograft
Xenograft developed
Other Names:
  • Patient-Derived Xenograft
  • Patient-Derived Xenograft Model
  • PDTX
  • PDX

Other: Personalized Medicine
Receive treatment based on the results of the PDX models




Primary Outcome Measures :
  1. Feasibility defined as available patient-derived xenograft (PDX) results before relapse [ Time Frame: Up to 1 year ]
    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 :
  1. Objective response (OR) rate (complete + partial responses) [ Time Frame: Up to 1 year ]
    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.

  2. Incidence of adverse events [ Time Frame: Up to 1 year ]
    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.

  3. Progression-free survival (PFS) [ Time Frame: Up to 1 year ]
    The distribution of PFS will be estimated using the method of Kaplan and Meier. Cox proportional hazard regression will be employed for multivariate analysis.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03219047


Contacts
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Contact: Michael Wang 713-792-2860 miwang@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Luhua (Michael) Wang    713-792-2860      
Principal Investigator: Luhua (Michael) Wang         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Luhua (Michael) Wang M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03219047     History of Changes
Other Study ID Numbers: 2017-0051
NCI-2018-01117 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0051 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 17, 2017    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin