Acalabrutinib Lenalidomide and Rituximab for the Treatment of CD20 Positive Stage III-IV Grade 1-3a Follicular Lymphoma

STATUS

Recruiting
End date

Mar 1, 2025
participants needed

24
sponsor

M.D. Anderson Cancer Center

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Updated on 19 February 2024

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cancer

blood transfusion

platelet count

ct scan

absolute neutrophil count

measurable disease

gilbert's syndrome

neutrophil count

monoclonal antibodies

growth factor

international normalized ratio

cervical cap

rituximab

lymphoma

monoclonal antibody therapy

tumor cells

human chorionic gonadotropin

positron emission tomography

beta-human chorionic gonadotropin

lenalidomide

monoclonal protein

follicular lymphoma

aptt

revlimid

bone marrow procedure

beta human chorionic gonadotropin

prothrombin

antibody therapy

beta-hcg

acalabrutinib

follicular lymphoma, grade 1

oral contraceptives

follicular large cell lymphoma

grade 3 follicular lymphoma

stage iii grade 1 follicular lymphoma

stage iv grade 2 follicular lymphoma

stage iv grade 3 follicular lymphoma

stage iii grade 3 follicular lymphoma

stage iv grade 1 follicular lymphoma

stage iii grade 2 follicular lymphoma

grade 3a follicular lymphoma

grade 1 follicular lymphoma

grade 2 follicular lymphoma

Summary

This phase II trial studies how well acalabrutinib, lenalidomide, and rituximab work in treating patients with CD20 positive stage III-IV, grade 1-3a follicular lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Rituximab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib, lenalidomide, and rituximab may help to control the disease.

Description

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in patients with previously untreated follicular lymphoma (FL) (determined by complete remission [CR] rate by the end of treatment).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy of acalabrutinib combined with rituximab and lenalidomide in subjects with FL as assessed by objective response rate (ORR) at the end of treatment, duration of response (DOR), progression rate within 24 months from treatment initiation (progression-free survival [PFS] 24), PFS and overall survival (OS).

II. To evaluate the safety and tolerability of acalabrutinib combined with rituximab and lenalidomide in previously untreated subjects with FL.

EXPLORATORY OBJECTIVE:

I. To determine the pharmacodynamic effects and investigate biomarkers of response and resistance of the 3-drug combination.

OUTLINE

Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Beginning cycle 2, patients receive lenalidomide PO once daily (QD) on days 1-21 and rituximab intravenously (IV) on days 1, 8, 15, and 22 of cycle 2 and day 1 of subsequent cycles. Treatment repeats every 28 days for 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 2 years.

Details

Condition	Ann Arbor Stage III Grade 1 Follicular Lymphoma, Ann Arbor Stage III Grade 2 Follicular Lymphoma, Ann Arbor Stage III Grade 3 Follicular Lymphoma, Ann Arbor Stage IV Grade 1 Follicular Lymphoma, Ann Arbor Stage IV Grade 2 Follicular Lymphoma, Ann Arbor Stage IV Grade 3 Follicular Lymphoma, Grade 3a Follicular Lymphoma
Age	18-100 years
Treatment	Rituximab, Lenalidomide, Acalabrutinib
Clinical Study Identifier	NCT04404088
Sponsor	M.D. Anderson Cancer Center
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Histologically confirmed CD20 positive (+) follicular lymphoma, grade 1, 2, or 3a
	Have had no prior systemic treatment for lymphoma
	Bi-dimensionally measurable disease, with at least one mass lesion >= 2 cm in longest diameter by computed tomography (CT), positron emission tomography (PET)/CT, and/or magnetic resonance imaging (MRI)
	Meeting Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria for initiation of treatment
	Stage III or IV disease
	Eastern Cooperative Oncology Group (ECOG) performance status =< 2
	Absolute neutrophil count (ANC) >= 1,000/mm^3, independent of growth factor support (within 28 days prior to signing informed consent)
	Platelet counts >= 100,000/mm^3 or >= 50,000/mm^3 if bone marrow involvement with lymphoma, independent of transfusion support in either situation (within 28 days prior to signing informed consent)
	Hemoglobin > 8 g/dL, independent of transfusion support (within 28 days prior to signing informed consent)
	Serum aspartate transaminase (AST) or alanine transaminase (ALT) < 2 x upper limit of normal (ULN) (within 28 days prior to signing informed consent)
	Creatinine clearance > 30 ml/min calculated by modified Cockcroft-Gault formula (within 28 days prior to signing informed consent)
	Bilirubin < 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL (within 28 days prior to signing informed consent)
	Prothrombin time (PT)/international normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN (within 28 days prior to signing informed consent)
	Must be able to adhere to the study visit schedule and other protocol requirements
	Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study (females of childbearing potential: must either completely abstain from heterosexual sexual conduct or must use 2 methods of reliable contraception, 1 highly effective [intrauterine device, birth control pills, hormonal patches, injections, vaginal rings, or implants] and at least 1 additional method [condom, diaphragm, cervical cap] of birth control). Reliable contraceptive methods must be started at least 4 weeks before lenalidomide, and continued for at least 4 weeks after last dose of lenalidomide. Males who are sexually active must be practicing complete abstinence or agree to a condom during sexual contact with a pregnant female or female of child bearing potential. Men must agree to not donate sperm during and after the study. For females, these restrictions apply at least 4 weeks before study treatment, during the period of therapy and for 1 month after the last dose of study drug. For males, these restrictions apply during the period of therapy and for 3 months after the last dose of study drug
	Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
	Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategies (REMS) program
	Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study
	All study participants must be registered into the mandatory Revlimid REMS program, and be willing and able to comply with the requirements of the REMS program
Exclusion Criteria
	Known active central nervous system lymphoma or leptomeningeal disease, except subjects with a history of central nervous system lymphoma treated and in remission > 6 months
	Evidence of diffuse large B-cell transformation
	Grade 3b FL
	Any prior history of other malignancy besides FL or marginal zone lymphoma, unless the patient has been free of disease for >= 5 years and felt to be at low risk for recurrence by the treating physician, except
	Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
	Adequately treated cervical carcinoma in situ without evidence of disease
	Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib or lenalidomide capsules, or put the study outcomes at undue risk
	Known history of human immunodeficiency virus (HIV), or active hepatitis C Virus, or active hepatitis B Virus infection, or any uncontrolled active significant infection, including suspected or confirmed John Cunningham (JC) virus infection
	Patients with inactive hepatitis B infection must adhere to hepatitis B reactivation prophylaxis unless contraindicated. Hepatitis B or C serologic status: subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative
	Concurrent systemic immunosuppressant therapy (e.g., cyclosporine, tacrolimus, etc., or chronic administration glucocorticoid equivalent of > 10 mg/day of prednisone) within 28 days of the first dose of study drug
	Known anaphylaxis or immunoglobulin (Ig) E-mediated hypersensitivity to murine proteins or to any component of acalabrutinib, lenalidomide and/or rituximab
	Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon). If patients have been on warfarin or equivalent vitamin K antagonists in the past, they will not be eligible if administered within 30 days of the first dose of study drug
	Requires chronic treatment with strong CYP3A inhibitors, for a list of strong CYP3A inhibitors. If patients have been on a strong CYP3A inhibitor in the past, they will not be eligible if the CYP3A inhibitor was administered within 7 days of the first dose of study drug
	Requires chronic treatment with strong CYP3A inducers, for a list of strong CYP3A inducers. If patients have been on a strong CYP3A inducer in the past, they will not be eligible if the CYP3A inducer was administered within 7 days of the first dose of study drug
	Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association functional classification. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study
	Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block, type II AV block, or 3rd degree block
	Active bleeding or known bleeding diathesis (e.g., von Willebrand's disease) or hemophilia
	History of stroke or intracranial hemorrhage within 6 months prior to study entry
	Vaccinated with live, attenuated vaccines within 4 weeks of study entry
	Lactating or pregnant subjects
	Administration of any investigational agent within 28 days of first dose of study drug
	Patients who have undergone major surgery within 28 days or minor surgery within 3 days of first dose of study drug
	Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisone (over these 4 weeks)
	Life expectancy < 6 months
	Neuropathy > grade 1
	Prior exposure to lenalidomide or to a BCR inhibitor, independently from indication
	Patient who require treatment with proton pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole), and are unable to switch to H2-receptor antagonists
	Patients who have difficulty with or are unable to swallow oral medication, or have disease significantly affecting gastrointestinal function that would limit absorption of oral medication
	Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP)
	Known history of deep vein thrombosis or pulmonary embolism
	Known history of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) or drug rash with eosinophilia and systemic symptoms (DRESS)

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measurable disease

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monoclonal antibodies

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international normalized ratio

cervical cap

rituximab

lymphoma

monoclonal antibody therapy

tumor cells

human chorionic gonadotropin

positron emission tomography

beta-human chorionic gonadotropin

bone marrow procedure

beta human chorionic gonadotropin

follicular lymphoma, grade 1

oral contraceptives

follicular large cell lymphoma

grade 3 follicular lymphoma

stage iii grade 1 follicular lymphoma

stage iv grade 2 follicular lymphoma

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stage iii grade 3 follicular lymphoma

stage iv grade 1 follicular lymphoma

stage iii grade 2 follicular lymphoma

grade 3a follicular lymphoma

grade 1 follicular lymphoma

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Study Definition

Wikipedia

Acalabrutinib Lenalidomide and Rituximab for the Treatment of CD20 Positive Stage III-IV Grade 1-3a Follicular Lymphoma