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

Sponsor:	Pharmacyclics
Information provided by (Responsible Party):	Pharmacyclics
ClinicalTrials.gov Identifier:	NCT01292135

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 Diffuse Well-differentiated Lymphocytic Lymphoma	Drug: PCI-32765	Phase 1 Phase 2

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:

MedlinePlus related topics: Acute Lymphocytic Leukemia Chronic Lymphocytic Leukemia Leukemia Lymphoma

Drug Information available for: Cyclophosphamide Tyrosine Bendamustine hydrochloride Bendamustine Fludarabine Fludarabine phosphate Rituximab

U.S. FDA Resources

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 ]

Estimated Enrollment:	60
Study Start Date:	February 2011
Estimated Study Completion Date:	March 2013
Estimated Primary Completion Date:	July 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:

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01292135

Locations

United States, Georgia
Emory University, Winship Cancer Institute
Atlanta, Georgia, United States, 30322
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:

Eric Hedrick, MD

Pharmacyclics

More Information

Additional Information:

www.pharmacyclics.com This link exits the ClinicalTrials.gov site

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
Last Updated:	February 23, 2012
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
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Nitrogen Mustard Compounds

Bendamustine
Fludarabine
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

ClinicalTrials.gov processed this record on May 14, 2012