Acalabrutinib for the Treatment of Ibrutinib-Intolerant Mantle Cell Lymphoma

Running, not enrolling · Phase 2

Conditions studied: Mantle Cell Lymphoma

In brief

This phase II trial studies how well acalabrutinib works in treating patients with mantle cell lymphoma that cannot tolerate ibrutinib. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Key facts

Study ID: NCT04189757
Run by: M.D. Anderson Cancer Center
People needed: 9
Starts: 2020-08-07
Expected to finish: 2027-06-30
Last updated by the study team: 2026-04-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Confirmed diagnosis of mantle cell lymphoma with CD20 positivity and chromosome translocation t(11;14), (q13;q32) and/or overexpress cyclin D1 in tissue biopsy
Include patients who require treatment (versus watch/wait)
Prior treatment with ibrutinib discontinued for reasons other than progression
Ibrutinib intolerance is defined as unacceptable toxicity where, in the opinion of the investigator, treatment should be discontinued in spite of optimal supportive care as a result of one of the following:
2 or more grade >= 2 non-hematological toxicities; OR
1 or more grade 3 >= 3 non-hematological toxicity; OR
1 or more grade 3 neutropenia with infection or fever; OR,
Grade 4 hematologic toxicity which persists to the point that the investigator chose to stop therapy due to toxicity NOT progression
Toxicity must have resolved to =< grade 1 prior to acalabrutinib dosing
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 infiltration by mantle cell lymphoma (MCL) are eligible if their ANC is >= 500/mm\^3 (growth factor allowed) or their platelet level is equal to or > 20,000/mm\^3. These patients should be discussed with either the principal investigator (PI) or co-PI of the study for final approval
Platelet count > 75,000/mm\^3
Patients who have bone marrow infiltration by MCL are eligible if their ANC is >= 500/mm\^3 (growth factor allowed) or their platelet level is equal to or > 20,000/mm\^3. These patients should be discussed with either the PI or co-PI of the study for final approval
Serum bilirubin < 1.5 mg/dl
Creatinine (Cr) clearance minimum to 30 mL/min per the Cockcroft-Gault formula as acalabrutinib pharmacokinetic (PK) has not been evaluated in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 29 mL/min/1.7 3\^m2, MDRD) or renal impairment requiring dialysis
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 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. 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 prior to starting therapy. Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for one week after the last dose of acalabrutinib. For male subjects with a pregnant or non-pregnant WOCBP partner, should use barrier contraception even if they have had a successful vasectomy
Patients who were not placed originally on ibrutinib by the providers due to concerns for worsening of comorbidities due to ibrutinib, such as atrial fibrillation can be included after cardiology clearance
Patients with well-controlled human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) would be eligible

You may not qualify if…

Prior treatment with acalabrutinib
History of BTK mutations conferring resistance to BTK inhibitors. Known mutations in the BTK gene that confer resistance to ibrutinib in mantle cell lymphoma include (e.g. BTK C481S, C481R mutations)
Progressive disease while on ibrutinib therapy. Patients who progressed while on ibrutinib therapy will be excluded from the study, patients who discontinue ibrutinib due to anaphylaxis or hypersensitivity reaction related to ibrutinib will be excluded from participation in the study
Known history of drug-specific hypersensitivity or anaphylaxis to ibrutinib (including active product or excipient components)
Pregnant or breast-feeding females
Patients with active hepatitis B infection. Those with prior hepatitis (hep)-B vaccination (i.e., anti-HBs antibody positive) or natural immunity as evidenced by the presence of anti-HBs and 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 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 BTK inhibitors and these patients would not be eligible for single agent acalabrutinib as proposed in this study
Active bleeding, history of bleeding diathesis (such as hemophilia or Von-Willebrand 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)
Ongoing adverse events from prior ibrutinib therapy (except persistent hematologic toxicity if meeting entry criteria). The PI should determine if AEs are an ongoing sequel of prior BTK therapy such as fungal infections, skin rash, diarrhea, fatigue, cramps and colitis or if the patient has resolved AE and is free of these adverse events >= 2 months after stopping ibrutinib)
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 > 10 mg prednisone or equivalent per day
Requires treatment with strong CYP3A inhibitors or inducers
Any of the following cardiac related conditions:
New York Heart Association (NYHA) class III and IV heart failure,
Active/symptomatic coronary artery disease,
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 interval [QTc] > 500 msec),

Where it is running

M D Anderson Cancer Center — Houston, Texas, United States

Full record on ClinicalTrials.gov

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