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

Small Lymphocytic Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01292135
• Other study ID #: PCYC-1108-CA
• Secondary ID: PCI-32765
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2011
• Last updated: July 17, 2014
• Start date: February 2011
• Est. completion date: May 2013

Study information

• Verified date: July 2014
• Source: Pharmacyclics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: May 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

Intervention

Drug:
• PCI-32765
420 mg daily

Locations

Country	Name	City	State
United States	Dana Farber Cancer Center	Boston	Massachusetts
United States	MD Anderson	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	CLL Research and Treatment Program	New Hyde Park	New York
United States	Weill Medical College of Cornell University	New York	New York
United States	University of Rochester	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
Pharmacyclics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Prolonged Hematologic Toxicity Started in Cycle 1		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.	Yes
Secondary	Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib		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.	Yes
Secondary	Overall Incidence of Grade =3 Adverse Events (AEs) Per NCI CTCAE V4.0		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.	Yes
Secondary	Overall Incidence of Serious Adverse Events (SAEs)		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.	Yes
Secondary	Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])	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.	No
Secondary	Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline		From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.	No
Secondary	Progression Free Survival Rate at 12 Months	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.	No

External Links

•   www.pharmacyclics.com