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Recurrent Mantle Cell LymphomaEarly Phase 1NCT03219047

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

A Early Phase 1 study testing Best Practice, Ibrutinib and Patient Derived Xenograft in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Best Practice, Ibrutinib and Patient Derived Xenograft
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1 participants
Where
1 siteUnited States
Study dates
20 Dec 2018to 3 Jul 2023
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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.

  1. 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:

  1. 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:

  1. 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.

Being tested
Best Practice, Ibrutinib, Patient Derived Xenograft, Personalized Medicine
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Best PracticeOther

    Also called standard of care, standard therapy

    Receive standard of care

  • IbrutinibDrug

    Also called BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

    Given at standard dose and schedule

  • Patient Derived XenograftOther

    Also called Patient-Derived Xenograft, Patient-Derived Xenograft Model, PDTX, PDX

    Xenograft developed

  • Personalized MedicineOther

    Receive treatment based on the results of the PDX models

Study groups in NCT03219047
Study groupRoleWhat they receive
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.
Receives: Other: Best Practice; Drug: Ibrutinib; Other: Patient Derived Xenograft; Other: Personalized Medicine
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.
Receives: Other: Best Practice; Other: Patient Derived Xenograft; Other: Personalized Medicine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 1 year

Secondary outcomes (3)

  1. 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.

    Measured: Up to 1 year

  2. 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.

    Measured: Up to 1 year

  3. 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.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2017
  2. Study start20 Dec 2018
  3. Primary completion3 Jul 2023
  4. Study completion3 Jul 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03219047
Sponsor's protocol ID
2017-0051
Other IDs
NCI-2018-01117, 2017-0051
Status last verified
Jul 2023
First submitted
13 Jul 2017
Last updated
27 Jul 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Best Practice, Ibrutinib and Patient Derived Xenograft in people with Recurrent Mantle Cell Lymphoma and Refractory Mantle Cell Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Feasibility defined as available patient-derived xenograft (PDX) results before relapse (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03219047.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jul 2023.

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