A Study of Acalabrutinib vs Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in R/R CLL

Running, not enrolling · Phase 3

Conditions studied: Chronic Lymphocytic Leukemia

In brief

This study is designed to evaluate the efficacy of acalabrutinib compared with rituximab in combination with idelalisib or bendamustine in previously treated subjects with chronic lymphocytic leukemia (CLL).

Key facts

Study ID

NCT02970318

Run by

Acerta Pharma BV

People needed

310

Starts

2017-02-02

Expected to finish

2027-10-01

Last updated by the study team

2026-07-24

Who can join

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

You may qualify if…

• Men and women ≥ 18 years of age.
• ECOG performance status of 0 to 2.
• Diagnosis of CLL that meets published diagnostic criteria (Hallek 2008):
• Monoclonal B-cells (either kappa or lambda light chain restricted) that are clonally co-expressing ≥ 1 B-cell marker (CD19, CD20, or CD23) and CD5.
• Prolymphocytes may comprise ≤ 55% of blood lymphocytes.
• Presence of ≥ 5 x 10\^9 B lymphocytes/L (5000/μL) in the peripheral blood (at any point since initial diagnosis).
• Must have documented CD20-positive CLL.
• Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL).
• Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
• Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
• Progressive lymphocytosis with an increase of > 50% over a 2-month period or a LDT of < 6 months. LDT may be obtained by linear regression extrapolation of ALC obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 x 10\^9/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
• Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
• Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:
• i. Unintentional weight loss ≥ 10% within the previous 6 months before screening.
• ii. Significant fatigue (ECOG performance score 2; inability to work or perform usual activities).
• iii. Fevers higher than 100.5°F or 38.0°C for ≥ 2 weeks before screening without evidence of infection.
• iv. Night sweats for > 1 month before screening without evidence of infection.
• Meet the following laboratory parameters:
• ANC ≥ 750 cells/μL (0.75 x 10\^9/L), or ≥ 500 cells/μL (0.50 x 10\^9/L) in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
• Platelet count ≥ 50,000 cells/μL (50 x 10\^9/L), or ≥ 30,000 cells/μL (30 x 10\^9/L) in subjects with documented bone marrow involvement, and without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded. If an Investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be ≥ 75,000 cells/μL (75 x 10\^9/L).
• Serum AST and ALT ≤ 2.0 x ULN.
• Total bilirubin ≤ 1.5 x ULN.
• Estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female].
• Must have received ≥ 1 prior systemic therapies for CLL. Note: Single-agent steroids or localized radiation are not considered a prior line of therapy. If a single-agent anti-CD20 antibody was previously administered, subjects must have received ≥ 2 doses.

You may not qualify if…

• Known CNS lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
• Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone or equivalent).
• Prior exposure to a BCL-2 inhibitor (e.g., venetoclax/ABT-199) or a BCR inhibitor (e.g., BTK inhibitors or PI3K inhibitors). Prior bendamustine is allowed if Investigator's choice for treatment in Arm B is idelalisib with rituximab. Bendamustine retreatment is allowed if the prior response to bendamustine lasted > 24 months.
• Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
• Corticosteroid use > 20 mg daily prednisone equivalent within 1 week before first dose of study drug, except as indicated for other medical conditions such as inhaled steroid for asthma, topical steroid use, or as premedication for administration of study drug or contrast. For example, subjects requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering are excluded.
• Prior radio- or toxin-conjugated antibody therapy.
• Prior allogeneic stem cell transplant or prior autologous transplant within 6 months of first dose of study drug(s) or presence of graft-vs-host disease or receiving treatment for graft-vs-host disease.
• Major surgical procedure within 30 days of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
• History of prior malignancy except for the following:
• Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician.
• Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer.
• Adequately treated carcinoma in situ without current evidence of disease.
• Significant cardiovascular disease such as uncontrolled or untreated 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 QTc > 480 msec (calculated using Fridericia's formula: QT/RR\^0.33) at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach, or extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
• Received a live virus vaccination within 28 days of first dose of study drug.
• Known history of infection with HIV or any uncontrolled active systemic infection (e.g., bacterial, viral, or fungal). For study sites in Germany: active infection with human immunodeficiency virus (seropositivity for HIV-1 or HIV-2 antibodies, and if positive, reactivity against the HIV-specific p24 antigen).
• Active CMV infection (active viremia as evidenced by positive polymerase chain reaction [PCR] result for CMV DNA).
• Serologic status reflecting active hepatitis B or C infection.
• Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative PCR result before randomization. Those who are 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 before randomization. Those who are hepatitis C PCR positive will be excluded.
• Ongoing, drug-induced liver injury, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
• History of or ongoing drug-induced pneumonitis.
• History of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis.
• History of stroke or intracranial hemorrhage within 6 months before first dose of study drug.

Where it is running

• Research Site — Oxnard, California, United States
• Research Site — Athens, Georgia, United States
• Research Site — Joliet, Illinois, United States
• Research Site — Cedar Rapids, Iowa, United States
• Research Site — Mount Sterling, Kentucky, United States
• Research Site — Saint Cloud, Minnesota, United States
• Research Site — Lincoln, Nebraska, United States
• Research Site — Brick, New Jersey, United States
• Research Site — Nyack, New York, United States
• Research Site — Canton, Ohio, United States
• Research Site — Fort Sam Houston, Texas, United States
• Research Site — Round Rock, Texas, United States
• Research Site — Adelaide, Australia
• Research Site — Box Hill, Australia
• Research Site — Frankston, Australia
• Research Site — Geelong, Australia
• Research Site — Gosford, Australia
• Research Site — Hobart, Australia
• Research Site — Kogarah, Australia
• Research Site — Murdoch, Australia
• Research Site — Nedlands, Australia
• Research Site — South Brisbane, Australia
• Research Site — Woodville, Australia
• Research Site — Linz, Austria
• Research Site — Chandler, Arizona, United States

Full record on ClinicalTrials.gov

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