| Eligibility |
- INCLUSION CRITERIA:
- Patients must have a confirmed histologic diagnosis of an indolent CD20 positive
B-cell lymphoma according to the criteria established by the 2016 version of the World
Health Organization (WHO) classification system. Lymphomas with any prior CD20
expression (by immunohistochemistry or flow cytometry) will be considered eligible.
Diagnosis must be confirmed by Laboratory of Pathology, NCI and the following indolent
B-cell lymphomas are included:
- Follicular lymphoma (FL): must be grade 1-2 or 3a
- Marginal zone lymphoma (MZL)
- Mantle cell lymphoma (MCL)
- Chronic lymphocytic leukemia (CLL)
- Participant must have relapsed and/or refractory disease, as defined below:
- FL: relapsed after and/or refractory to at least two (2) prior lines of therapy with
at least one of those therapies containing an anti-CD20 monoclonal antibody.
NOTE: Participants with FL may be eligible after one (1) prior line of therapy if they have
either:
- Follicular lymphoma international prognostic index (FLIPI) >=2 (120)
- Disease progression within 24 months of the end of last therapy (POD24)
- MZL: relapsed after and/or refractory to at least two (2) prior lines of therapy, with
at least one containing an anti-CD20 monoclonal antibody.
- MCL: relapsed after and/or refractory to at least two (2) prior lines of therapy, with
at least one containing an anti-CD20 monoclonal antibody.
NOTE: Participants with MCL may be eligible after one (1) prior line of therapy if they
have either:
- Blastoid or pleomorphic histology
- 17p deletion
- TP53 mutation or deletion
- Ki67 >=30%
- Received a BTK inhibitor as first line therapy
- CLL: relapsed after and/or refractory to at least two (2) prior lines of therapy.
Participants with CLL are not required to have had therapy containing anti-CD20.
NOTE: Participants with CLL may be eligible after one (1) prior line of therapy if they
have either:
- 17p deletion
- TP53 mutation or deletion
- Received both a Bruton s Tyrosine Kinase (BTK) inhibitor AND a B-cell lymphoma 2
(BCL2) inhibitor as first line therapy
NOTE: Participants must not have received prior treatment with a CD47 or SIRP targeting
agent
-Adequate tissue from diagnostic biopsy (archival or fresh) must be available for
performance of correlative studies
NOTE: Tumor tissue may be from any previously collected tissue and adequacy is at the
discretion of the Principal Investigator. If prior tissue is not available, patient must be
willing to undergo baseline tissue biopsy (for patients with known or suspected bone marrow
involvement, bone marrow may be acceptable tissue per discretion of the investigator).
-Patients must have at least evaluable disease as assessed by clinical exam (i.e., palpable
lymphadenopathy, measurable skin lesions, etc.), laboratory assessment (i.e., lymphoma
involvement of bone marrow or peripheral blood by morphology, cytology or flow cytometry),
and/or imaging (measurable lymph nodes or masses on CT or MRI and/or evaluable FDG-avid
lesions on PET). Patients may also have measurable disease.
NOTE: Patients with known active CNS lymphoma are not eligible.
- Age greater than or equal to 18 years
NOTE: Because no dosing or adverse event data are currently available on the use of
magrolimab in patients <18 years of age, children are excluded from this study
- ECOG performance status less than or equal to 2
- Adequate organ function as evidenced by the following laboratory parameters:
- Absolute neutrophil count (ANC): greater than or equal to 1,000/mm(3)
- Platelets: greater than or equal to 50,000/mcL (transfusions permitted)
- Hemoglobin: greater than or equal to 9 g/dL (transfusions permitted). NOTE:
Patients must have required fewer than 2 units of RBC transfusion in the 4 weeks
prior to screening. Additional transfusions after screening and prior to
enrollment are acceptable.
- Renal function: Glomerular filtration rate (GFR) greater than or equal to 30
mL/min/1.73 m(2) as estimated by the Modification of Diet in Renal Disease (MDRD)
abbreviated formula. If not on target, a 24-hour urine creatinine clearance can
be used to directly measure.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): less than or
equal to 3.0 x the upper ULN
NOTE: Patients with liver involvement with lymphoma less than or equal to 5.0 x ULN
-Bilirubin less than or equal to 1.5 X ULN
NOTE: Patients with Gilbert's syndrome may have a bilirubin level > 1.5 X ULN, per
discretion of the investigator
-The effects of the study drugs on the developing human fetus are unknown. For this reason,
women of childbearing potential (WOCBP) and men must agree to use effective contraception
when sexually active. This applies for the time period between signing of the informed
consent form and for the following time frames after the last dose of drug, whichever is
later: 90 days after the last dose of magrolimab, 30 days after the last dose of
venetoclax, and 18 months after the last dose of obinutuzumab for women and 6 months after
the last dose of obinutuzumab for men. Men should refrain also from donating sperm for
these same timeframes, and women must also refrain from donating eggs.
NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone
successful surgical sterilization or who is not postmenopausal (i.e., amenorrheic for >12
months without alternative medical cause; post-menopausal status in females under 55 years
of age should be confirmed with a serum follicle-stimulating hormone [FSH] level within
applicable local laboratory reference range for postmenopausal women). Permanent
sterilization methods include but are not limited to hysterectomy, bilateral salpingectomy
and bilateral oophorectomy. The investigator or a designated associate is requested to
advise the patient how to achieve highly effective birth control (failure rate of less than
1%), e.g., intrauterine device (IUD), intrauterine hormone-releasing system (IUS),
bilateral tubal occlusion, vasectomized partner and sexual abstinence. The use of condoms
by male patients is required unless the female partner is permanently sterile.
- Ability of patient to understand and the willingness to sign a written informed
consent document
- Patients with prior autologous or allogeneic stem cell transplantation are potentially
eligible if transplanted > 6 months ago, and no active graft-vs-host disease requiring
immunosuppressants.
EXCLUSION CRITERIA:
- Concomitant use of any investigational anti-lymphoma treatment
- Known primary or acquired immunodeficiency syndrome (e.g., HIV) or known infection
with human T-cell leukemia virus 1 (HTLV1). NOTE: HIV-positive patients on combination
antiretroviral therapy are ineligible because of the potential for pharmacokinetic
interactions with the study drugs. In addition, these patients are at increased risk
of lethal infections when treated with marrow-suppressive therapy. In the future,
appropriate studies will be undertaken in patients receiving combination
antiretroviral therapy when indicated.
- History of hemolytic anemia or autoimmune thrombocytopenia in the 3 months prior to
enrollment. Patients with positive Direct Agglutination Test (DAT) but no evidence of
clinically active hemolysis are eligible.
- Hepatitis B surface antigen or hepatitis B DNA PCR positive. NOTE: Subjects who are
hepatitis B core antibody positive will need to have a negative HBV DNA PCR result
before enrollment. Those with a positive PCR for hepatitis B are excluded.
- Pregnant or breastfeeding patients. NOTE: Pregnant women are excluded in this study
because of the potential for teratogenic or abortifacient effects. Because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with the study drugs, breastfeeding should be discontinued.
- Requirement to continue on any of the medications that have significant potential for
drug-drug interactions with the study regimen. For example, the following:
- Use of strong CYP3A inhibitors 7 days prior to or at initiation of venetoclax,
and during ramp-up phase is contraindicated in patients with MZL, CLL and MCL.
For FL patients, use of strong CYP3A inhibitors is contraindicated 7 days prior
to and during the first two weeks of venetoclax treatment.
- Consumption of one or more of the following within 3 days prior to the first dose
of any study drug:
- Grapefruit or grapefruit products
- Seville oranges including marmalade containing Seville oranges
- Star fruit
- Uncontrolled intercurrent illness including, but not limited to the following that may
limit interpretation of results or that could increase risk to the patient at the
discretion of the investigator:
- Active hepatitis C infection. NOTE: Subjects who are hepatitis C antibody
positive will need to have a negative HCV PCR result before enrollment. Those
with a positive PCR for hepatitis C are excluded.
- Any second malignancy that requires active systemic therapy
- Known mental or physical illness that would interfere with cooperation with the
requirements of the trial or confound the results or interpretation of the
results of the trial and, in the opinion of the treating investigator, would make
the patient inappropriate for entry into the study
- Known active infection, or any major infection requiring treatment with IV
antibiotics or hospitalization within 4 weeks prior to commencement of the study
treatment.
- Vaccination with a live vaccine less than or equal to 28 days prior to commencement of
the study treatment.
- Inability or unwillingness to swallow a large number of tablets.
- Known hypersensitivity to any of the study medications or their excipients.
- History of inflammatory bowel disease (e.g., Crohn s disease or ulcerative colitis).
- History of malabsorption syndrome felt to be significant enough to interfere with
enteral absorption at the discretion of the investigator.
|
