Trial Title:
Phase 2 Open Label Randomized Study of Pirtobrutinib and Brexucabtagene Autoleucel in R/R MCL
NCT ID:
NCT06553872
Condition:
Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Brexucabtagene autoleucel
Pirtobrutinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pirtobrutinib
Description:
Pirtobrutinib is a non-covalent BTKi that has preserved activity in the presence of
mutations that drive BTKi resistance.
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Jaypirca
Intervention type:
Drug
Intervention name:
Brexucabtagene Autoleucel
Description:
Brexucabtagene autoleucel is an autologous CD19-directed chimeric antigen receptor (CAR)
T-cell therapy (brexu-cel).
Arm group label:
Arm A
Arm group label:
Arm B
Other name:
Tecartus
Summary:
This is a phase 2, open-label, randomized, multicenter clinical trial in patients with
relapsed/refractory mantle cell lymphoma (R/R MCL) who meet the criteria for
standard-of-care FDA label for CD19 CAR T-cell therapy with brexucabtagene autoleucel
(brexu-cel).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patients with a histologically confirmed diagnosis of mantle cell lymphoma (MCL)
will be eligible.
- Adult males or females who are 18 years of age or older at time of signing informed
consent.
- Must have ability to comprehend and the willingness to sign written informed consent
for study participation.
- Eligible to receive CAR T-cell therapy (Brexucabtagene autoleucel) for MCL by the
standard of care label, which states: "TECARTUS or Brexucabtagene autoleucel is a
CD19-directed genetically modified autologous T-cell immunotherapy indicated for the
treatment of: Adult patients with relapsed or refractory mantle cell lymphoma (MCL)"
- ECOG performance status 0 to 2.
- Patients are required to have the following washout periods prior to leukapheresis.
In addition, prior treatment-related AEs must have recovered to Grade ≤ 1 with the
exception of alopecia and Grade 2 peripheral neuropathy.
- Targeted agents (i.e. BTK inhibitors), investigational agents, therapeutic
monoclonal antibodies or cytotoxic chemotherapy: 5 half-lives or 2 weeks,
whichever is shorter
- Antibody-drug conjugates (ADC): 10 weeks
- Radiation therapy: Broad field radiation (≥ 30% of the bone marrow or whole
brain radiotherapy): 14 days. Palliative limited field radiation: 7 days. Note:
In the case of known central nervous system (CNS) involvement by systemic
lymphoma: Patients with previous treatment for CNS involvement who are
neurologically stable and without evidence of disease may be eligible if a
compelling clinical rationale is provided by the Investigator and with
documented Sponsor approval.
- Bendamustine or other purine analogues: 3 months.
- Corticosteroids: 5 days
- The effects of Pirtobrutinib on the developing human fetus are unknown. For this
reason and because other therapeutic agents used in this trial are known to be
teratogenic, women of child-bearing potential and men must agree to use adequate
contraception (hormonal or barrier method of birth control; abstinence) prior to
study entry and for the duration of study participation as outlined in criteria
below:
- Men must agree to take appropriate precautions to avoid fathering children
(with at least 99% certainty) from screening through safety follow up and must
refrain from donating sperm during this period. Permitted methods that are at
least 99% effective in preventing pregnancy should be communicated to the
participants in their understanding confirmed.
- Willingness of women of reproductive potential and their partners to observe
highly effective birth control methods for the duration of treatment and for 1
month following the last dose of study treatment (see Section 4.3 and Section
4.4 for further details)
- Women of childbearing potential must have a negative serum pregnancy test at
screening and before the first dose of pirtobrutinib and must agree to take
appropriate precautions to avoid pregnancy (with at least 99% certainty) from
screening through safety follow up. Permitted methods that are at least 99%
effective in preventing pregnancy should be communicated to the participants
and their understanding confirmed.
- Women of non-childbearing potential (i.e. surgically sterile with a
hysterectomy and/or bilateral oophorectomy OR >= 12 months of amenorrhea) are
eligible.
- Patients must meet the following laboratory parameters at screening:
- Hematology (criteria the same regardless of bone marrow involvement; must be
independent of transfusions and G-CSF support within 7 days of assessment)
- Platelets >= 50 x 10^9/L
- Hemoglobin >= 8g/dL
- Absolute Neutrophil Count >=1.0 x 10^9/L
- Hepatic
- ALT < 2.5 x ULN for age, <5 x ULN in the presence of liver metastases
- AST < 2.5 x ULN for age, <5 x ULN in the presence of liver metastases
- Total bilirubin < 1.5 x ULN or <3 x ULN in the presence of documented
Gilbert's syndrome unconjugated hyperbilirubinemia)
- Renal Creatinine clearance >= 30 mL/minute based on Cockcroft-Gault formula.
- Cardiopulmonary Cardiac LVEF >=40% confirmed by ECHO/multigated analysis
- Adequate pulmonary function <= Grade 2 dyspnea and <= Grade 2 hypoxia per CTCAE
v5.0.
- Adequate coagulation, defined as activated partial thromboplastin time (aPTT)
or partial thromboplastin time (PTT) and prothrombin (PT) or (international
normalized ratio (INR) not greater than 1.5 x ULN.
Exclusion Criteria:
- Patients who have previously received treatment with pirtobrutinib for >2 months
prior to study enrollment are ineligible. Patients who are relapsed or refractory
and then received less than 2 months of pirtobrutinib as "holding therapy" while
awaiting CAR T-cell therapy evaluation, and who did not demonstrate disease
progression while on pirtobrutinib holding therapy, are eligible.
- Patients who have previously discontinued pirtobrutinib due to disease progression,
intolerance, or toxicity.
- Patients who are currently receiving or who have received any investigational study
agent ≤4 weeks prior to screening visit are ineligible.
- Prior treatment with chimeric antigen receptor (CAR) T-cell therapy.
- Participants with clinically significant or uncontrolled cardiac disease, including
unstable angina or acute coronary syndrome within the past 2 months prior to
randomization, history of myocardial infarction within 3 months prior to
randomization, documented LVEF by any method of ≤ 40% in the 12 months prior to
randomization, or ≥ Grade 3 NYHA functional classification system of heart failure.
- Uncontrolled or symptomatic arrhythmias, including prolongation of the QT interval
corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's
Formula (QTcF): QTcF = QT/(RR0.33). Correction of suspected drug induced QTcF
prolongation can be attempted at the investigator's discretion and only if
clinically safe to do so with either discontinuation of the offending drug or switch
to another drug not known to be associated with QTcF prolongation. Correction for
underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are
eligible if they have no history of fainting or clinically relevant arrhythmias
while using the pacemaker
- Evidence of active uncontrolled/untreated infection (viral, bacterial, fungal,
opportunistic) of any origin.
- Participants with active immunologic or inflammatory/autoimmune disease affecting
the CNS, and unrelated to their disease under study or previous treatment.
- Patients with active CNS involvement of Mantle Cell Lymphoma. A history of CNS
Mantle Cell Lymphoma is allowed, as long as it has cleared, and the patient is able
to comply with study procedures. Patients with previous treatment for CNS
involvement who are neurologically stable and without evidence of disease may be
eligible with documented Sponsor approval.
- Known positive Human immunodeficiency virus (HIV) status. For patients with unknown
HIV status, HIV testing will be performed at Screening and result must be negative
for enrollment.
- Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg)
are excluded. Patients with positive hepatitis B core antibody (anti-HBc) and
negative HBsAg require a negative hepatitis B polymerase chain reaction (PCR)
evaluation before randomization. Patients who are HBV DNA PCR positive will be
excluded. Patients who are HBV DNA PCR negative with positive anti-HBc require
prophylaxis against Hepatitis B reactivation (see Section 6.4 "General Guidance for
Hepatic Monitoring").
- Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C
antibody result, patient will need to have a negative result for hepatitis C
ribonucleic acid (RNA) before randomization. Patients who are hepatitis C RNA
positive will be excluded.
- Known active cytomegalovirus (CMV) infection. Unknown or negative status are
eligible.
- Participants who require the concurrent use of chronic systemic steroids or
immunosuppressant medications. Steroids should not be given within 5 days prior to
leukapheresis. Concomitant bridging steroids (section 6.6) are allowed after
leukapheresis.
- Known hypersensitivity or severe reaction to pirtobrutinib, similar compounds, or
excipients.
- Participants who have not recovered from adverse events (AEs) due to prior
anticancer therapy (i.e., have residual toxicities > Grade 1), with the exception of
stable Grade 2 peripheral neuropathy and/or any grade alopecia.
- Pregnant or nursing (breast-feeding) women are excluded from this study because
there is an unknown but potential risk to using pirtobrutinib in pregnant or nursing
women. Patients are excluded if they are pregnant or plan to become pregnant during
the study or within 1 year of the last dose of study treatment. Patients are also
excluded if they are lactating or plan to breastfeed during the study or within 1
week of the last dose of study treatment. Please see Section 4.3 and Section 4.4 for
General Guidance for Women of Child Bearing Potential and/or Use of Contraceptive
Methods.
- Any condition that would, in the investigator's judgement, interfere with full
participation in the study, including administration of pirtobrutinib and attending
required study visits (if outpatient); pose a significant risk to the participant;
or interfere with interpretation of study data.
- Inability of the participant to swallow and retain oral medication. Or, if there is
clinically significant active malabsorption syndrome or other condition likely to
affect gastrointestinal (GI) absorption of the study drug.
- Patients who experienced a major bleeding event or grade ≥ 3 arrhythmia on prior
treatment with a BTK inhibitor. NOTE: Major bleeding is defined as bleeding having
one or more of the following features: potentially life-threatening bleeding with
signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in
the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or
organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial
bleeding or intramuscular bleeding with compartment syndrome)
- Major surgery within 4 weeks prior to enrollment.
- History of a previously diagnosed hereditary bleeding disorder.
- Patients requiring therapeutic anticoagulation with warfarin or another vitamin K
antagonist.
- Active second malignancy unless in remission and with life expectancy > 2 years.
- Vaccination with live vaccine within 28 days prior to randomization.
- History of stroke or intracranial hemorrhage within 6 months of enrollment.
- History of allogeneic or autologous stem cell transplant within 60 days of
enrollment, presence of either of the following regardless of prior stem cell
transplant timing: active graft vs. host disease; cytopenias from incomplete blood
cell count recovery post-transplant.
- Active uncontrolled autoimmune cytopenia, including autoimmune hemolytic anemia or
idiopathic thrombocytopenic purpura for which new therapy was introduced or existing
therapy was escalated within the 4 weeks prior to study enrollment to maintain
adequate blood counts.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Stanford Cancer Center
Address:
City:
Stanford
Zip:
94305
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Saurabh Dahiya, MD
Phone:
650-724-4155
Investigator:
Last name:
Saurabh Dahiya, MD
Email:
Sub-Investigator
Facility:
Name:
Univ of Miami - Sylvester Comprehensive Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Jay Spiegel, MD
Phone:
305-243-5302
Investigator:
Last name:
Jay Spiegel, MD
Email:
Sub-Investigator
Facility:
Name:
Moffitt Cancer Center
Address:
City:
Tampa
Zip:
33612
Country:
United States
Status:
Recruiting
Contact:
Last name:
Ruthie Chae
Phone:
813-745-3425
Email:
ruthie.chae@moffitt.org
Investigator:
Last name:
Michael Jain, MD, PhD
Email:
Principal Investigator
Investigator:
Last name:
Julio Chavez, MD
Email:
Sub-Investigator
Investigator:
Last name:
Sameh Gaballa, MD
Email:
Sub-Investigator
Investigator:
Last name:
Farhad Khimani, MD
Email:
Sub-Investigator
Investigator:
Last name:
Aleksandr Lazaryan, MD, PhD
Email:
Sub-Investigator
Investigator:
Last name:
Frederick Locke, MD
Email:
Sub-Investigator
Investigator:
Last name:
Sayeef Mirza, MD
Email:
Sub-Investigator
Investigator:
Last name:
Taiga Nishihori, MD
Email:
Sub-Investigator
Investigator:
Last name:
Bijal Shah, MD
Email:
Sub-Investigator
Start date:
August 23, 2024
Completion date:
August 2029
Lead sponsor:
Agency:
H. Lee Moffitt Cancer Center and Research Institute
Agency class:
Other
Collaborator:
Agency:
Bankhead-Coley Florida Biomedical Research Program
Agency class:
Other
Collaborator:
Agency:
Eli Lilly and Company
Agency class:
Industry
Source:
H. Lee Moffitt Cancer Center and Research Institute
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06553872
