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Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01292135
First received: February 2, 2011
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to establish the safety of orally administered PCI-32765 in combination with fludarabine/cyclophosphamide/rituximab (FCR) and bendamustine/rituximab (BR) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma(SLL).


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Drug: PCI-32765
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b, Multicenter, Open-label, Parallel-group Safety Study of a Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI 32765, in Combination With Chemotherapy in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Incidence of Prolonged Hematologic Toxicity Started in Cycle 1 [ Time Frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib [ Time Frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: Yes ]
  • Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0 [ Time Frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: Yes ]
  • Overall Incidence of Serious Adverse Events (SAEs) [ Time Frame: From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: Yes ]
  • Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR]) [ Time Frame: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: No ]
    Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. Assessment of response to treatment will be done every 2 cycles for the first 6 months and then every 3 months thereafter until disease progression or prior to the administration of a new anticancer therapy and at follow-up visits.

  • Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline [ Time Frame: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: No ]
  • Progression Free Survival Rate at 12 Months [ Time Frame: From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest. ] [ Designated as safety issue: No ]
    Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.


Enrollment: 33
Study Start Date: February 2011
Study Completion Date: May 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR) Drug: PCI-32765
420 mg daily
Experimental: PCI-32765 plus bendamustine/rituximab (BR) Drug: PCI-32765
420 mg daily

Detailed Description:

This is a Phase 1b, open-label, parallel-group, nonrandomized, multicenter study of PCI 32765 420 mg once daily oral (PO) administration in combination with 2 different chemotherapy regimens in subjects with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed CLL or SLL and satisfying at least 1 of the following criteria for requiring treatment:

    • 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° 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
  2. 1 to 3 prior treatment regimens for CLL/SLL
  3. ECOG performance status of ≤ 1
  4. ≥ 18 years of age
  5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
  6. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

Exclusion Criteria:

  1. Any chemotherapy, therapeutic antineoplastic antibodies (not including radio- or toxin immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4 weeks of first dose of study drug
  2. Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
  3. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
  4. Transformed lymphoma or Richter's transformation Any 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
  5. Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) < 1000 cells/mm3 (1.0 x 109/L) oPlatelet count < 50,000/mm3 (50 x 109/L) oSerum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) oCreatinine > 2.0 x ULN or creatinine clearance < 40 mL/min
  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: NCT01292135

Locations
United States, Massachusetts
Dana Farber Cancer Center
Boston, Massachusetts, United States, 02115
United States, New York
CLL Research and Treatment Program
New Hyde Park, New York, United States, 11042
Weill Medical College of Cornell University
New York, New York, United States, 10065
University of Rochester
Rochester, New York, United States, 14642
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pharmacyclics
Investigators
Study Director: Thorsten Graef, MD Pharmacyclics
  More Information

Additional Information:
No publications provided

Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01292135     History of Changes
Other Study ID Numbers: PCYC-1108-CA, PCI-32765
Study First Received: February 2, 2011
Results First Received: February 28, 2014
Last Updated: July 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Pharmacyclics:
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, B-Cell
Bruton's Tyrosine Kinase

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014