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Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL (PCYC-1109-CA)

This study has been completed.
Sponsor:
Collaborator:
Ohio State University
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01217749
First received: October 7, 2010
Last updated: May 28, 2015
Last verified: May 2015
  Purpose
The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases

Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Prolymphocyctic Leukemia
Richter's Transformation
Drug: PCI-32765
Drug: ofatumumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Percentage of Participants Achieving Response [ Time Frame: The median follow-up time on study for all treated participants is 12.5 (range 0.5-19.6) months ] [ Designated as safety issue: No ]
    The primary endpoint for the study was overall response rate (ORR), defined as the proportion of participants who achieved a best overall response of complete response (CR), CR with incomplete blood count recovery (Cri), or partial response (PR), according to the guidelines from the International Workshop on Chronic Lymphocytic Leukemia (IWCLL1) published in 2008 for CLL participants and International Working Group for non-Hodgkin's lymphoma (IWG NHL) 2007 criteria for SLL participants, with the modification that treatment-related lymphocytosis will not be considered progressive disease, as evaluated by the investigators. Assessment of disease is based on radiological exams, physical exam, hematological evaluations and, when appropriate, bone marrow results.

  • Safety During Dose-Limiting Toxicity (DLT) Observation Period [ Time Frame: 56 days for Group 1 and 28 days for Group 2 ] [ Designated as safety issue: Yes ]
    Number of dose-limiting toxicities observed in the first 6 participants enrolled in treatment Groups 1 and 2


Secondary Outcome Measures:
  • Number of Participants With Treatment Emergent Adverse Events (AEs) [ Time Frame: From first dose of study treatment to within 30 days of last dose or until study closure ] [ Designated as safety issue: Yes ]
    Number of participants who had experienced at least one treatment emergent AE

  • Progression Free Survival (PFS) at 12 Months [ Time Frame: From first dose of study treatment until disease progression, death, or until 12 months ] [ Designated as safety issue: No ]

    Progressive disease for CLL (Hallek) is characterized by ≥1 of the following:

    • Appearance of any new lesion, eg lymph nodes (> 1.5 cm), de novo hepatomegaly or splenomegaly, or other organ infiltrates
    • Increase of ≥50%

      • in longest diameter of any previous site
      • in hepatomegaly or splenomegaly
      • in blood lymphocytes with ≥5x109/L B cells with enlarging lymph node, liver, or spleen

    Progressive disease for B cell lymphoma (Cheson) is characterized by any new lesion or increase by ≥ 50% of previously involved sites from nadir:

    • Appearance of a new lesion(s) >1.5 cm in any axis, ≥ 50% increase in the SPD of >1 node, or ≥50% increase in longest diameter of a previously identified node >1 cm in short axis
    • Lesions PET+ if FDG-avid lymphoma or PET+ before therapy
    • 50% increase from nadir in the SPD of any liver or spleen lesions
    • New or recurrent BM involvement
    • Increase of ≥50% in blood lymphocytes with ≥5x109/L B cells within enlarging lymph node, liver, or spleen


Enrollment: 71
Study Start Date: December 2010
Study Completion Date: May 2014
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
In Group 1, PCI-32765 420 mg PO was administered daily for 1 cycle (28 days) before the start of ofatumumab IV dosing
Drug: PCI-32765
420 mg PO daily
Other Name: ibrutinib
Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra
Experimental: Group 2
In Group 2, PCI-32765 420 mg PO daily was initiated concomitantly with ofatumumab IV (PCI-32765 initiated on Day 2 of Cycle 1)
Drug: PCI-32765
420 mg PO daily
Other Name: ibrutinib
Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra
Experimental: Group 3
In Group 3, two cycles of ofatumumab IV were administered prior to the start of PCI-32765 420 mg PO daily
Drug: PCI-32765
420 mg PO daily
Other Name: ibrutinib
Drug: ofatumumab
per package insert as an IV infusion
Other Name: Arzerra

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL), or Richter's transformation arising out of CLL/SLL as defined by WHO classification of hematopoietic neoplasms and satisfying ≥ 1 of the following conditions:

    • Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
    • Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement
    • Presence of unintentional weight loss > 10% over the preceding 6 months
    • NCI CTCAE Grade 2 or 3 fatigue
    • Fevers > 100.5 degree or night sweats for > 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months
    • Need for cytoreduction prior to stem cell transplant
  2. Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to such therapy
  3. 10% expression of CD20 on CLL/SLL cells
  4. ECOG performance status ≤ 2
  5. Life expectancy ≥ 12 weeks
  6. Subjects must have organ and marrow function as defined below:

    • Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow involvement
    • Platelets ≥ 30,000/μL in the absence of bone marrow involvement
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal unless due to Gilbert's disease
    • AST (SGOT) ≤ 2.5 x institutional upper limit of normal unless due to infiltration of the liver
    • Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min
  7. No history of prior exposure to ofatumumab
  8. Age ≥ 18 years
  9. Body weight ≥ 40 kg

Exclusion Criteria:

  1. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
  2. Significant cardiovascular disease
  3. Any condition which could interfere with the absorption or metabolism of PCI-32765 including unable to swallow capsules, 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
  4. Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection
  5. Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug. Corticosteroids for disease-related symptoms are allowed provided 1 week washout occurs
  6. Active central nervous system (CNS) involvement by lymphoma
  7. Major surgery within 4 weeks before first dose of study drug
  8. Lactating or pregnant
  9. Known moderate to severe chronic obstructive pulmonary disease (COPD)
  10. History of prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
  11. History of Grade ≥ 2 toxicity continuing from prior anticancer therapy including radiation
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01217749

Locations
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Pharmacyclics
Ohio State University
Investigators
Principal Investigator: Samantha Jaglowski, MD Ohio State University
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01217749     History of Changes
Other Study ID Numbers: PCYC-1109-CA  PCI-32765 
Study First Received: October 7, 2010
Results First Received: April 2, 2015
Last Updated: May 28, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016