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Acalabrutinib in Combination With Obinutuzumab in Relapsed/Refractory or Untreated CLL/SLL/PLL

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ClinicalTrials.gov Identifier: NCT02296918
Recruitment Status : Recruiting
First Posted : November 21, 2014
Last Update Posted : February 7, 2018
Sponsor:
Information provided by (Responsible Party):
Acerta Pharma BV

Brief Summary:
To evaluate the safety and preliminary efficacy of acalabrutinib in combination with obinutuzumab in 4 separate cohorts of patients.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Prolymphocytic Leukemia Drug: acalabrutinib Drug: Obinutuzumab Drug: Venetoclax Drug: Rituximab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of ACP-196 in Combination With Obinutuzumab for Patients With Relapsed / Refractory or Untreated CLL/SLL/PLL
Study Start Date : November 2014
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022


Arm Intervention/treatment
Experimental: Double combo with acalabutinib in RR
For Relapse Refractory subjects, acalabrutinib starting at Cycle 1 as monotherapy then combine with obinutuzumab starting at Cycle 2 for 6 cycles.
Drug: acalabrutinib
100 mg twice daily continuous
Other Name: ACP-196

Drug: Obinutuzumab
Cycle 2 Day 1, 100 mg IV will be administered. Then on Cycle 2 Day 2, 900 mg administered. On Cycle 2 Days 8 and 15, 1000 mg IV will be administered. On Cycles 3-7, 1000 mg on Day 1 of each cycle will be administered.
Other Name: Gazyva

Experimental: Double combo with acalabutinib in TN
For previously untreated subjects, acalabrutinib starting at Cycle 1 as monotherapy then combine with obinutuzumab starting at Cycle 2 for 6 cycles.
Drug: acalabrutinib
100 mg twice daily continuous
Other Name: ACP-196

Drug: Obinutuzumab
Cycle 2 Day 1, 100 mg IV will be administered. Then on Cycle 2 Day 2, 900 mg administered. On Cycle 2 Days 8 and 15, 1000 mg IV will be administered. On Cycles 3-7, 1000 mg on Day 1 of each cycle will be administered.
Other Name: Gazyva

Experimental: Triplet combo with acalabutinib in RR
For Relapse Refractory subjects, acalabrutinib starting at Cycle 1 as monotherapy then combine with rituximab starting at Cycle 2 for 6 cycles. Venetoclax, starting at Cycle 3 taken up to 12 cycles
Drug: acalabrutinib
100 mg twice daily continuous
Other Name: ACP-196

Drug: Venetoclax
20 mg daily for 1 week, 50 mg daily for 1 week, 100 mg daily for 1 week, 200 mg daily for 1 week, then 400 mg daily for duration of treatment.
Other Names:
  • ABT-199
  • Venclexta

Drug: Rituximab
Rituximab will be given at a starting dose of 375 mg/m2 on Day 1 of Cycle 2, followed by 375 mg/m2 every week for 3 doses and then every 4 weeks for 5 doses for a total of 9 infusions
Other Name: Rituxan

Experimental: Triplet combo with acalabutinib in TN
For previously untreated subjects, acalabrutinib starting at Cycle 1 as monotherapy then combine with obinutuzumab starting at Cycle 2 for 6 cycles. Venetoclax, starting at Cycle 3 taken up to 12 cycles
Drug: acalabrutinib
100 mg twice daily continuous
Other Name: ACP-196

Drug: Obinutuzumab
Cycle 2 Day 1, 100 mg IV will be administered. Then on Cycle 2 Day 2, 900 mg administered. On Cycle 2 Days 8 and 15, 1000 mg IV will be administered. On Cycles 3-7, 1000 mg on Day 1 of each cycle will be administered.
Other Name: Gazyva

Drug: Venetoclax
20 mg daily for 1 week, 50 mg daily for 1 week, 100 mg daily for 1 week, 200 mg daily for 1 week, then 400 mg daily for duration of treatment.
Other Names:
  • ABT-199
  • Venclexta




Primary Outcome Measures :
  1. Overall Response Rate (ORR) in cohort 1 and cohort 2 [ Time Frame: 12 Months ]
    To determine the overall response rate (ORR) at 12 months with the combination of acalabrutinib plus obinutuzumab in subjects with relapsed or refractory chronic lymphocytic leukemia (CLL)

  2. Evaluating safety in combination with acalabrutinib [ Time Frame: 24 Months ]
    To establish the safety of the combination of acalabrutinib, rituximab and venetoclax in relapsed and refractory subjects and acalabrutinib, obintuzumab and venetoclax in the previously untreated subjects by evaluating Treatment Emergent Adverse Events as assessed by CTCAE v4.03


Secondary Outcome Measures :
  1. ORR for treatment with ventoclax [ Time Frame: 16 Months ]
    To evaluate the ORR of the combination therapy of acalabrutinib plus venetoclax plus an anti-CD20 antibody at Cycle 16



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients with a diagnosis of intermediate or high risk CLL (or variant immunophenotype), SLL, or B-PLL by IWCLL 2008 criteria (48) who have:

  • Previously received at least one therapy for their disease.
  • Previously untreated disease and 65 years old OR under 65 years old and or refuse or are ineligible for chemoimmunotherapy

All patients must satisfy one of the following criteria for active disease requiring therapy:

  • Evidence of marrow failure as manifested by the development or worsening of anemia or thrombocytopenia
  • Massive (≥ 6 cm below the costal margin), progressive or symptomatic splenomegaly
  • Massive nodes (≥ 10 cm) or progressive or symptomatic lymphadenopathy
  • Constitutional symptoms, which include any of the following:

    • Unintentional weight loss of 10% or more within 6 months
    • Significant fatigue limiting activity
    • Fevers ≥100.5 degrees F for 2 weeks or more without evidence of infection
    • Night sweats >1 month without evidence of infection
  • Patients with a history of Richter's transformation are eligible if they now have evidence of CLL only, with <10% large cells in the bone marrow.
  • ECOG performance status ≤ 2
  • Life expectancy of < 2 years or that would confound assessment of toxicity in this study
  • Must be ≥ 18 years of age

Exclusion Criteria:

  • Any life-threatening illness, medical condition, or organ dysfunction which, in the investigator's opinion, could compromise the subjects' safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
  • Subjects with active cardiovascular disease not medically controlled or those who have had myocardial infarction in the past 6 months, or corrected QT interval (QTc) ≥480 ms.
  • Malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel or gastric bypass, ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
  • Grade ≥2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.
  • History of a bleeding diathesis (eg, hemophilia, Von Willebrand disease).
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura.
  • History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
  • Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 28 days of first dose of study drug.
  • Requires treatment with proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
  • Subjects with history of or ongoing drug-induced pneumonitis.
  • Subjects with human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) or any uncontrolled active systemic infection.
  • Subjects who are known to have hepatitis B infection or who are hepatitis B core antibody or surface antigen positive.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02296918


Contacts
Contact: Tasheda Navarro +1 650 670 5439 t.navarro@acerta-pharma.com

Locations
United States, Ohio
Recruiting
Columbus, Ohio, United States
Sponsors and Collaborators
Acerta Pharma BV

Responsible Party: Acerta Pharma BV
ClinicalTrials.gov Identifier: NCT02296918     History of Changes
Other Study ID Numbers: ACE-CL-003
First Posted: November 21, 2014    Key Record Dates
Last Update Posted: February 7, 2018
Last Verified: February 2018

Keywords provided by Acerta Pharma BV:
CLL
SLL
PLL
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Prolymphocytic Leukemia
ACP-196
acalabrutinib
obinutuzumab
rituximab
venetoclax

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Prolymphocytic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Obinutuzumab
Venetoclax
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents