Acalabrutinib and Rituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma

• Status: Not yet recruiting
• Trial end date: 2022-08-22
• Target enrollment: 0
• Participant gender: All

Summary

This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill cancer cells. Giving acalabrutinib and rituximab may help to control mantle cell lymphoma in elderly patients.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Acalabrutinib; Antibodies; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Immunoglobulins; Rituximab

Criteria

Inclusion Criteria:

• Pathology confirmed diagnosis of mantle cell lymphoma with CD20 positivity and chromosome translocation t (11;14), (q13;q32) and/or positive cyclin D1 in tissue biopsy

• Newly diagnosed elderly MCL (age >= 65 years) with no prior therapy under all risk categories

• Patients with preexisting well-controlled cardio-vascular comorbidities - patients on anticoagulants (excluding warfarin and vitamin K antagonists), antiplatelet, anti-hypertensive, prior ablation, anti-arrhythmia, prior arrhythmias, baseline electrocardiogram (EKG) abnormalities and cardiology clearance are allowed. Ejection fraction >= 50% and cardiology clearance are required

• Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form

• Bi-dimensional measurable disease using the Cheson criteria (measurable disease by positron emission tomography [PET]-computed tomography [CT] scan defined as at least 1 lesion that measures >= 1.5 cm in single dimension.) Gastrointestinal, bone marrow or spleen only patients are allowable

• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

• Absolute neutrophil count (ANC) >= 1,000/mm^3 (Patients who have bone marrow and spleen infiltration by MCL are eligible, the ANC and platelets counts will not be limited)

• Platelet count >= 100,000/mm^3 (Patients who have bone marrow and spleen infiltration by MCL are eligible, the ANC and platelets counts will not be limited)

• Serum bilirubin =< 1.5 mg/dl

• Creatinine clearance minimum to 50 mL/min per the Cockcroft-Gault formula

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2 x upper limit of normal or =< 5 x upper limit of normal if hepatic metastases are present. Gilbert's disease is allowed

• Disease free of prior malignancies 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), not actively being treated with life expectancy of > 3 years. Principal investigator (PI) can use clinical judgement in the best interest of patients

• Women of childbearing potential (WOBP) must have a negative serum or urine pregnancy test. WOBP and males must be willing to use highly effective methods of birth control. therapy. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib and for 12 months following the last dose of rituximab. For male subjects with a pregnant or non-pregnant WOCBP partner, should use barrier contraception, during treatment and for 2 days after the last dose of acalabrutinib and for 1 month following the last dose of rituximab even if they have had a successful vasectomy

Exclusion Criteria:

• Patients with central nervous system involvement with mantle cell lymphoma or with suspected or confirmed progressive multifocal leukoencephalopathy (PML) are excluded since those patients have very poor prognosis, need aggressive intensive chemoimmunotherapy and intrathecal chemotherapy along with Bruton's tyrosine kinase (BTK) inhibitors and these patients would not be eligible for this study

• Pregnant or breast-feeding females

• Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication

• Known history of hypersensitivity or anaphylaxis to study drug(s) including active product or excipient components

• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (aPTT) (in the absence of lupus anticoagulant) > 2 x upper limit of normal (ULN)

• Concurrent participation in another therapeutic clinical trial

• Immunization with live vaccine within 4 weeks of and during therapy with rituximab

• Subjects who are hepatitis B or C polymerase chain reaction (PCR) positive. Those with prior hepatitis B (Hep-B) vaccination (i.e., hepatitis B surface antibody [anti-HBs] antibody positive) or natural immunity as evidenced by the presence of anti-HBs and hepatitis B core antibody (anti-HBc) positivity are eligible to enroll. (Known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal [GI] consultation)

• Patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)

• Active bleeding, history of bleeding diathesis (such as Hemophilia or Von-Willbrand disease), any history of intracranial bleed or stroke within 6 months of first dose of study drug

• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)

• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or any other gastrointestinal condition that could interfere with the absorption and metabolism of acalabrutinib

• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before first dose of study drug

• Major surgery within 4 weeks of initiation of therapy

• Requires anticoagulation with warfarin or equivalent vitamin K antagonist

• Concomitant use of corticosteroids at > 20 mg prednisone or equivalent per day > 2 weeks

• Requires treatment with strong CYP3A inhibitors or inducers

• Patients who have had a stroke within 6 months

• Any of the following conditions considered clinically significant cardiovascular diseases as determined after cardiology consultation:

• Diagnosed congestive heart failure

• Active/symptomatic coronary artery disease

• Congestive heart failure

• Myocardial infarction in the preceding 6 months

• Significant conduction abnormalities, including but not limited to:

• Left bundle branch block

• 2nd degree atrioventricular (AV) block type II

• 3rd degree block

• QT prolongation (corrected QT [QTc] > 480 msec)

• Sick sinus syndrome

• Ventricular tachycardia

• Symptomatic bradycardia (heart rate < 50 bpm)

• Persistent, controlled and uncontrolled atrial fibrillation

• Uncontrolled hypertension

• Hypotension

• Light headedness and syncope

• Active infection

• Acute infection requiring systemic anti-microbial treatment (systemic antibiotics, antivirals, or antifungals) within 14 days prior to initiation of therapy

• Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole or pantoprazole). Subjects receiving proton-pump inhibitors who switch to H2-receptor antagonists (2 hours after acalabrutinib/placebo) or antacid (2 hours before or 2 hours after acalabrutinib/placebo). Avoid co-administration with proton pump inhibitors

• Active infection including systemic fungal or cytomegalovirus (CMV) infection who were hospitalized in past 6 months

• Any other serious medical condition including, but not limited to, uncontrolled diabetes mellitus, uncontrolled thyroid disorder, uncontrolled hypertension (i.e. uncontrolled blood pressure [BP] - > 160/110 in spite of 3 different classes of full dose anti-hypertensives medications and in spite of cardiology evaluation; documentation from cardiology is required to say that the BP is uncontrollable), chronic obstructive pulmonary disease (COPD), renal failure, psychiatric illness or social circumstances that, in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form or complying with study procedures