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.
Information provided by (Responsible Party):
Pharmacyclics Identifier:
First received: February 2, 2011
Last updated: June 13, 2013
Last verified: June 2013

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:
  • To measure the number of participants with prolonged hematologic toxicity [ Time Frame: 8 weeks from first dose ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To measure the number of participants with adverse events as a measure of safety and tolerability [ Time Frame: For 30 days after the last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
  • To measure the number of patients who respond to treatment by measuring the increase or decrease of disease in the lymph nodes and/or blood test results [ Time Frame: Patients may remain on study until the last subject enrolled completes a maximum of 12 cycles of PCI-32765. Any subjects still receiving PCI-32765 at that time may enroll in a long-term follow-up study to continue to receive PCI-32765 capsules ] [ Designated as safety issue: No ]

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).


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

Inclusion Criteria:

  • 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
  • 1 to 3 prior treatment regimens for CLL/SLL
  • ECOG performance status of ≤ 1

    ≥ 18 years of age

  • Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
  • 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:

  • 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 Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
  • Concomitant use of medicines known to cause QT prolongation or torsades de pointes
  • 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
  • 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
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Please refer to this study by its identifier: NCT01292135

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
Study Director: Thorsten Graef, MD Pharmacyclics
  More Information

Additional Information:
No publications provided

Responsible Party: Pharmacyclics Identifier: NCT01292135     History of Changes
Other Study ID Numbers: PCYC-1108-CA, PCI-32765
Study First Received: February 2, 2011
Last Updated: June 13, 2013
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, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Nitrogen Mustard Compounds
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists processed this record on July 20, 2014