CompletedPhase 1

Acalabrutinib in Combination With Anti-CD20 and Venetoclax in Relapsed/Refractory or Untreated CLL/SLL/PLL

United States69 participantsStarted 2014-12-22

Plain-language summary

To evaluate the safety and preliminary efficacy of acalabrutinib in combination with obinutuzumab in 4 separate cohorts of participants.

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Participants with a diagnosis of intermediate or high risk CLL (or variant immunophenotype), SLL, or B-cell prolymphocytic leukemia (B-PLL) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Hallek et al. 2008) who have:
✓. Participants in Cohorts 1 and 3 may have received previous ibrutinib (or another Bruton tyrosine kinase (BTK) inhibitor) as long as discontinuation was for a reason other than on-treatment disease progression.
✓. All participants must satisfy one of the following criteria for active disease requiring therapy:
✓. This criterion was removed with Amendment 5.
✓. Participants with a history of Richter's syndrome are eligible if they now have evidence of CLL only, with \<10% large cells in the bone marrow.
✓. Participants must have adequate organ function, defined as creatinine ≤2.5 times the upper limit of normal range (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, and bilirubin ≤2.5 x ULN. For Cohorts 3 and 4, participants must have creatinine clearance ≥50 mL/min using modified Cockcroft-Gault equation (using Ideal Body Mass \[IBM\] instead of mass):
✓. IBM (kg) = \[(height cm - 154) ● 0.9\] + (50 if male, 45.5 if female).
✓. Platelets \>50 x 10\^9/L. In participants with CLL involvement of the marrow, \>30 x 10\^9/L for Cohorts 1 and 2. For Cohorts 3 and 4, participants must have hemoglobin \>9 g/dL.

Exclusion criteria

✕. For Cohorts 2 and 4, received previous therapy for CLL. Treatment of autoimmune complications of CLL with steroids or rituximab is allowed, however, CD20 must have returned on 10% of the CLL cells if rituximab was recently administered. Palliative steroids are acceptable at doses ≤20 mg prednisone equivalent daily.

What they're measuring

Percentage of Participants With Objective Response (OR) at 12 Months as Assessed by the Investigator in Cohorts 1 and 2

Timeframe: Day 1 through 12 months

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in all Cohorts

Timeframe: Day 1 through the final data cutoff date (approximately 6 years 8 months)

Number of Participants With Treatment-Emergent Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 Abnormalities in Laboratory Parameters in all Cohorts

Timeframe: Day 1 through the final data cutoff date (approximately 6 years 8 months)

Number of Participants With Abnormal Vital Signs Reported as TEAEs in all Cohorts

Timeframe: Day 1 through the final data cutoff date (approximately 6 years 8 months)

Number of Participants with Shift From Baseline to Worst (Grade 3 and 4) Post-baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status in all Cohorts

Timeframe: Baseline (Days -28 to -1) through the final data cutoff date (approximately 6 years 8 months)

Trial details

NCT IDNCT02296918

SponsorAcerta Pharma BV

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2021-08-20

View on ClinicalTrials.gov More Chronic Lymphocytic Leukemia trials

Who can participate

Age range18 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Participants with a diagnosis of intermediate or high risk CLL (or variant immunophenotype), SLL, or B-cell prolymphocytic leukemia (B-PLL) by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria (Hallek et al. 2008) who have:
✓. Participants in Cohorts 1 and 3 may have received previous ibrutinib (or another Bruton tyrosine kinase (BTK) inhibitor) as long as discontinuation was for a reason other than on-treatment disease progression.
✓. All participants must satisfy one of the following criteria for active disease requiring therapy:
✓. This criterion was removed with Amendment 5.
✓. Participants with a history of Richter's syndrome are eligible if they now have evidence of CLL only, with \<10% large cells in the bone marrow.
✓. Participants must have adequate organ function, defined as creatinine ≤2.5 times the upper limit of normal range (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN, and bilirubin ≤2.5 x ULN. For Cohorts 3 and 4, participants must have creatinine clearance ≥50 mL/min using modified Cockcroft-Gault equation (using Ideal Body Mass \[IBM\] instead of mass):
✓. IBM (kg) = \[(height cm - 154) ● 0.9\] + (50 if male, 45.5 if female).
✓. Platelets \>50 x 10\^9/L. In participants with CLL involvement of the marrow, \>30 x 10\^9/L for Cohorts 1 and 2. For Cohorts 3 and 4, participants must have hemoglobin \>9 g/dL.

Exclusion criteria

✕. For Cohorts 2 and 4, received previous therapy for CLL. Treatment of autoimmune complications of CLL with steroids or rituximab is allowed, however, CD20 must have returned on 10% of the CLL cells if rituximab was recently administered. Palliative steroids are acceptable at doses ≤20 mg prednisone equivalent daily.