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

July 17, 2014 updated by: Pharmacyclics LLC.

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Center
    • New York
      • New Hyde Park, New York, United States, 11042
        • CLL Research and Treatment Program
      • New York, New York, United States, 10065
        • Weill Medical College of Cornell University
      • Rochester, New York, United States, 14642
        • University of Rochester
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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.
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.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
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.
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.
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.
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.
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.
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.
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.
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
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.
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
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.
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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharmacyclics LLC.

Investigators

  • Study Director: Thorsten Graef, MD, Pharmacyclics LLC.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

November 1, 2012

Study Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

February 2, 2011

First Submitted That Met QC Criteria

February 8, 2011

First Posted (Estimate)

February 9, 2011

Study Record Updates

Last Update Posted (Estimate)

July 24, 2014

Last Update Submitted That Met QC Criteria

July 17, 2014

Last Verified

July 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PCYC-1108-CA
  • PCI-32765 (Other Identifier: Pharmacyclics)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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