Overview

Ibrutinib for the Treatment of Patients With B-Cell Malignancies Who Are Infected With Coronavirus Disease 2019 (COVID-19)

Status:
Not yet recruiting
Trial end date:
2025-05-01
Target enrollment:
0
Participant gender:
All
Summary
This phase II trial studies the effects of ibrutinib in treating patients with B-cell malignancies who are infected with COVID-19. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Ibrutinib is a first in class Bruton tyrosine kinase inhibitor (BTKi), for the treatment of B-cell malignancies. This study is being done to determine if taking ibrutinib after contracting COVID-19 will make symptoms better or worse.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Academic and Community Cancer Research United
Collaborator:
National Cancer Institute (NCI)
Criteria
Inclusion Criteria:

- REGISTRATION INCLUSION

- (COHORT 1): Age >= 18 years

- COHORT 1: Laboratory confirmed diagnosis of COVID-19 through confirmation of
SARS-Co-V2 via reverse transcriptase polymerase chain reaction (RT-PCR) or any Food
and Drug Administration (FDA) approved method. The date of test result is required to
be =< 7 days prior to registration (NOTE: please use the date the test was resulted
and NOT the date when the test was collected)

- COHORT 1: Patient is on ibrutinib for the following approved FDA indications,
including:

- Chronic lymphocytic leukemia/Small lymphocytic lymphoma

- Mantle cell lymphoma

- Waldenstrom macroglobulinemia

- Marginal zone lymphoma

- COHORT 1: Patients have been on standard dose ibrutinib therapy (420 mg daily for
chronic lymphocytic leukemia [CLL]/small lymphocytic lymphoma [SLL] and
Waldenstrom/Waldenstrom macroglobulinemia, and 560 mg daily for mantle cell lymphoma
and marginal zone lymphoma) for at least 6 months prior to diagnosis of COVID-19
infection; and there is no evidence of disease progression of the primary malignancy
for which ibrutinib is being used

- NOTE: Patients are allowed to receive standard treatment as per local
institutional guidelines for the treatment of COVID-19 at the same time the
patient is enrolled on this trial

- COHORT 1: Provide informed written consent =< 7 days prior to registration

- COHORT 1: Willing to return to enrolling institution for follow-up (during the active
monitoring phase of the study)

- Note: During the active monitoring phase of a study (i.e., active treatment and
clinical follow-up), participants must be willing to return to the consenting
institution for follow-up. All of these visits will be virtual (phone or video)
ONLY

- COHORT 1: Willing to provide blood specimens for correlative research purposes

- RANDOMIZATION INCLUSION

- COHORT 2: Age >= 18 years

- COHORT 2: Laboratory confirmed diagnosis of COVID-19 through confirmation of
SARS-Co-V2 via RT-PCR or any FDA approved method. The date of test result is required
to be =< 7 days prior to registration (NOTE: please use the date the test was resulted
and NOT the date when the test was collected)

- COHORT 2: Patient is on ibrutinib for the following approved FDA indications,
including:

- Chronic lymphocytic leukemia/Small lymphocytic lymphoma

- Mantle cell lymphoma

- Waldenstrom macroglobulinemia

- Marginal zone lymphoma

- COHORT 2: Patients have been on standard dose ibrutinib therapy (420 mg daily for
CLL/SLL and Waldenstrom macroglobulinemia, and 560 mg daily for mantle cell lymphoma
and marginal zone lymphoma) for at least 6 months prior to diagnosis of COVID-19
infection; and there is no evidence of disease progression of the primary malignancy
for which ibrutinib is being used

- NOTE: Patients are allowed to receive standard treatment as per local
institutional guidelines for the treatment of COVID-19 at the same time the
patient is enrolled on this trial

- COHORT 2: Provide informed written consent =< 7 days prior to registration

- COHORT 2: Willing to return to enrolling institution for follow-up (during the Active
Monitoring Phase of the study)

- Note: During the Active Monitoring Phase of a study (i.e., active treatment and
clinical follow-up), participants must be willing to return to the consenting
institution for follow-up. All of these visits will be virtual (phone or video)
ONLY

- COHORT 2: Willing to provide blood specimens for correlative research purposes

- COHORT 2: Absolute neutrophil count (ANC) > 750 cells/mm^3 (0.75 x 10^9/L)

- COHORT 2: Platelet count > 50,000 cells/mm^3 (50 x 10^9/L)

- COHORT 2: Estimated creatinine clearance (CrCl) >= 30 mL/min (Cockcroft-Gault)

- COHORT 2: Bilirubin =< 2.0 x upper limit of normal (ULN) (unless bilirubin rise is due
to Gilbert's syndrome or of non-hepatic origin)

- COHORT 2: Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 5 x ULN

- COHORT 2: Prothrombin time (PT)/International normal ratio (INR) < 1.5 x (upper limit
of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin
time [aPTT]) < 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or
bleeding disorder)

Exclusion Criteria:

- REGISTRATION EXCLUSION

- COHORT 1: Patient is receiving ibrutinib therapy for chronic graft-versus-host disease
(cGVHD)

- COHORT 1: Patient is currently receiving (or has in the past 6 months) another
treatment in combination with ibrutinib, such as anti-CD20 monoclonal antibody, BCL-2
antagonists such as venetoclax, or other novel treatments or chemotherapeutic agents.
For clarification regarding specific medications not listed here, please discuss with
the principal investigator

- COHORT 1: Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while
on study

- COHORT 1: Concomitant use of a strong CYP3A inhibitor

- COHORT 1: Vaccinated with a live, attenuated vaccine within 4 weeks

- COHORT 1: Patients with chronic liver disease and hepatic impairment meeting Child
Pugh class C

- COHORT 1: History of stroke or intracranial hemorrhage within 6 months before
registration

- COHORT 1: History of bleeding diathesis (e.g. hemophilia, von Willebrand/Waldenstrom
disease)

- COHORT 1: Clinically significant cardiovascular disease, such as uncontrolled
arrhythmia or class 3 or 4 congestive heart failure as defined by the New York Heart
Association Functional Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to registration

- COHORT 1: Chemotherapy for other malignancies

- COHORT 1: Concurrent systemic immunosuppressant therapy within 21 days of the first
dose of study drug with the exception of that which is part of the standard of care
for COVID-19

- COHORT 1: Major surgery within 4 weeks of registration

- COHORT 1: Female subjects who are pregnant, or breastfeeding, or planning to become
pregnant while enrolled in this study or within 1 month of last dose of study drug.
Male subjects who plan to father a child while enrolled in this study or within 3
months after the last dose of study drug

- RANDOMIZATION EXCLUSION

- COHORT 2: Patient is receiving ibrutinib on a clinical trial for their underlying
B-cell malignancy

- COHORT 2: Patient is receiving ibrutinib therapy for chronic graft-versus-host disease
(cGVHD)

- COHORT 2: Patient is currently receiving (or has in the past 6 months) another
treatment in combination with ibrutinib, such as anti-CD20 monoclonal antibody, BCL-2
antagonists such as venetoclax, or other novel treatments or chemotherapeutic agents.
For clarification regarding specific medications not listed here, please discuss with
the principal investigator

- COHORT 2: Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (e.g. phenprocoumon) within 7 days of first dose of study drug and while
on study

- COHORT 2: Concomitant use of a strong CYP3A inhibitor

- COHORT 2: Vaccinated with a live, attenuated vaccine within 4 weeks of registration

- COHORT 2: Patients with chronic liver disease and hepatic impairment meeting Child
Pugh class B and C

- COHORT 2: History of stroke or intracranial hemorrhage within 6 months before
registration

- COHORT 2: History of bleeding diathesis (e.g. hemophilia, von Willebrand disease)

- COHORT 2: Clinically significant cardiovascular disease, such as uncontrolled
arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart
Association Functional Classification; or a history of myocardial infarction, unstable
angina, or acute coronary syndrome within 6 months prior to registration

- COHORT 2: Chemotherapy for other malignancies

- COHORT 2: Concurrent systemic immunosuppressant therapy =< 21 days of the first dose
of study drug with the exception of that which is part of the standard of care for
COVID-19

- COHORT 2: Major surgery within 4 weeks of registration

- COHORT 2: Female subjects who are pregnant, or breastfeeding, or planning to become
pregnant while enrolled in this study or within 1 month of last dose of study drug.
Male subjects who plan to father a child while enrolled in this study or within 3
months after the last dose of study drug

- COHORT 2: Patients stopped ibrutinib >= 7 days prior to registration, for any reason

- COHORT 2: Patient is an active participant on investigational therapy through an
Institutional Review Board (IRB) approved clinical trial for COVID-19 (NOTE:
Participation through compassionate use protocol or expanded access is permitted)

- COHORT 2: At time of registration, the patient requires:

- Endotracheal intubation and mechanical ventilation