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.
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.
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.
