Chronic Lymphocytic Leukemia Clinical Trial
Acalabrutinib for the Treatment of Relapsed or Refractory Autoimmune Hemolytic Anemia in Patients With Chronic Lymphocytic Leukemia
This phase II trial studies the effect of acalabrutinib in treating autoimmune hemolytic anemia that has come back (relapsed) or has not responded to previous treatment (refractory) in patients with leukemia-cll/" >chronic lymphocytic leukemia. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
I. Assess the efficacy of acalabrutinib in chronic lymphocytic leukemia (CLL) patients with relapsed or refractory autoimmune hemolytic anemia (AIHA).
I. Evaluate acalabrutinib's ability to induce short term and sustained hemoglobin response.
II. Assess the toxicity of acalabrutinib. III. Evaluate efficacy of acalabrutinib in CLL.
I. Assess the effect of acalabrutinib on T-cell functionality in an autoimmune disorder.
Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Treatment with acalabrutinib may be continued beyond 12 cycles for a maximum of 36 cycles if, in the opinion of the treating physician, the patient might benefit from ongoing therapy.
After completion of study treatment, patients are followed up at 30 days and at least every 4 months for up to 12 months.
Documented informed consent of the participant and/or legally authorized representative
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Eastern Cooperative Oncology Group (ECOG) =< 2
"Warm" or "cold" AIHA in patients with CLL, relapsed/refractory (RR) after first line treatment with oral prednisone (with or without rituximab), defined as:
Anemia (hemoglobin [Hgb] =< 10 g/dL; or Hgb > 10 g/dL dependent on transfusions or maintenance therapy (rituximab, cyclosporin, etc) to maintain this level of hemoglobin, and
Laboratory evidence of hemolysis - presence of 3 of 4 markers (increased reticulocyte count, increased indirect bilirubin, increased lactate dehydrogenase, absent haptoglobin)
Positive direct antiglobulin test (DAT) (score >= 1+) - either immunoglobulin G (IgG) DAT, C3 DAT, or both. Eligibility of patients with Coombs-negative AIHA should be confirmed by the trial investigator at each respective study site
Histologically or flow cytometry confirmed diagnosis of CLL/small lymphocytic lymphoma (SLL)
Participant must be able to swallow tablets or capsules
Absolute neutrophil count (ANC) >= 500/mm^3 unless due to disease involvement in the bone marrow or autoimmune neutropenia (within 30 days prior to day 1 of protocol therapy)
Platelets >= 30,000/mm^3 unless due to disease involvement in the bone marrow or autoimmune thrombocytopenia (Evans syndrome) (within 30 days prior to day 1 of protocol therapy)
Direct bilirubin =< 3.0 x upper limit of normal (ULN) (within 30 days prior to day 1 of protocol therapy)
Aspartate aminotransferase (AST) =< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy)
Alanine aminotransferase (ALT) =< 3.0 x ULN (within 30 days prior to day 1 of protocol therapy)
Creatinine clearance of >= 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 30 days prior to day 1 of protocol therapy)
If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (prothrombin time [PT]) < 2 x ULN (within 30 days prior to day 1 of protocol therapy). If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants (within 30 days prior to day 1 of protocol therapy)
If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) < 2 x ULN (within 30 days prior to day 1 of protocol therapy). If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants (within 30 days prior to day 1 of protocol therapy)
Seronegative for human immunodeficiency virus (HIV) Ag/Ab combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR]) (within 30 days prior to day 1 of protocol therapy)
If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
Women of childbearing potential (WOCBP): negative urine or serum pregnancy test within the screening window prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Agreement by females of childbearing potential to use highly effective methods of birth control or abstain from heterosexual activity starting with the first dose of study therapy through 2 days after the last dose of protocol therapy
Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
Therapeutic anticancer antibodies within 3 weeks
Radio- or toxin-immunoconjugates within 10 weeks
BH3-mimetic venetoclax, PI3K inhibitors and other "targeted" therapy- within 6 half-lives
Ibrutinib, acalabrutinib or another BTK inhibitor within 12 months
Patients on stable chronic AIHA treatments are allowed provided the dose has not changed in the 4 weeks prior to enrollment
Allogeneic stem cell transplant within 1 year prior to day 1 of protocol therapy, or ongoing immunosuppressive therapy for chronic graft versus host disease (cGVHD)
Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
Strong CYP3A4 inducers/ inhibitors. If the patient requires a strong CYP3A inhibitor/inducer, they should not be enrolled even if it could be held for 14 days before the first dose of study drug
Proton pump inhibitors (but patients who switch to H2-receptor antagonists or antacids are eligible for enrollment)
Chronic use of corticosteroids (> 2 weeks) in excess of prednisone 60 mg/day or its equivalent within 4 weeks prior to start of study therapy. Rescue steroids are allowed during trial
Vitamin K antagonists
Known intolerance to acalabrutinib
History of bleeding disorders or with active bleeding
Patients with suspected or confirmed progressive multifocal leukoencephalopathy (PML)
Patients with history of stroke or intracranial hemorrhage within 6 months
Inadequate recovery from adverse events related to prior therapy to grade 1 or baseline (excluding grade 2 alopecia and neuropathy)
Active uncontrolled infection
Known history of immunodeficiency virus (HIV) infection
Subjects who have an undetectable or unquantifiable HIV viral load with CD4 > 300 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
Active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
Participants 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. Note that intravenous immunoglobulin therapy (IVIG) administration may lead to positive anti-HBc test result
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
Major surgery (requiring general anesthesia) within 28 days prior to initiation of therapy
Has difficulty with or is unable to swallow oral medication, or has significant gastrointestinal disease that would limit absorption of oral medication
History of prior malignancy except:
Malignancy treated with curative intent and no known active disease present for >= 2 years prior to initiation of therapy on current study
Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease
Adequately treated in situ carcinomas (e.g., breast, cervical, esophageal, etc.) without evidence of disease
Asymptomatic prostate cancer managed with "watch and wait" strategy
Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or left ventricular ejection fraction (LVEF) =< 40%
Psychiatric illness/social situations that would limit compliance with study requirements
Participant is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics
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There is 1 Location for this study
Duarte California, 91010, United States
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