Study of the Safety and Tolerability of PCI-32765 in Patients With Recurrent B Cell Lymphoma

NCT ID: NCT00849654

Last Updated: 2013-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2012-07-31

Brief Summary

The purpose of this study is to establish the safety and optimal dose of orally administered PCI-32765 in patients with recurrent B cell lymphoma.

Conditions

B-Cell Lymphoma; B-Cell Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PCI-32765

Group Type: EXPERIMENTAL

PCI-32765

Intervention Type: DRUG

In the dose-escalation cohorts, PCI-32765 will be administered in 1.25, 2.5, 5.0, 8.3, 12.5, and 17.5 mg/kg/d dose orally once per day for 28 days followed by a 7-day rest period to determine the MTD. If MTD is not reached, dosing levels may be increased beyond 17.5mg/kg/d by 33% increments.

In the continuous dosing cohorts, PCI-32765 will be administered in 8.3 mg/kg/day and 560 mg/day (fixed dose) dose orally once per day for 35 days.

Interventions

PCI-32765

In the dose-escalation cohorts, PCI-32765 will be administered in 1.25, 2.5, 5.0, 8.3, 12.5, and 17.5 mg/kg/d dose orally once per day for 28 days followed by a 7-day rest period to determine the MTD. If MTD is not reached, dosing levels may be increased beyond 17.5mg/kg/d by 33% increments.

In the continuous dosing cohorts, PCI-32765 will be administered in 8.3 mg/kg/day and 560 mg/day (fixed dose) dose orally once per day for 35 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women and men ≥ 18 years of age. There is no experience with this drug in a pediatric population.
• Body weight ≥ 40 kg.
• Recurrent surface immunoglobulin positive B cell non-Hodgkin's lymphoma (NHL) according to WHO classification, including small lymphocytic lymphoma/ chronic lymphocytic leukemia (SLL/CLL) lymphoplasmacytic lymphoma, including Waldenström's Macroglobulinemia (WM), and pre-identified DLBCL ABC subtype oFor the DLBCL-ABC cohort, documented, activated B-cell subtype by either immunohistochemistry or tissue microarray analysis.
• Measurable disease (for NHL, bidimensional disease ≥ 2 cm diameter in at least one dimension, for CLL ≥ 5000 leukemia cells/mm3, for WM presence of immunoglobulin M paraprotein with a minimum IgM level ≥ 1000 mg/dL and infiltration of bone marrow by lymphoplasmacytic cells), and pre-identified DLBCL ABC subtype by immunohistochemistry (IHC).
• Have failed ≥ 1 previous treatment for lymphoma and no standard therapy is available. Patients with diffuse large B cell lymphoma must have failed, refused or be ineligible for autologous stem cell transplant.
• ECOG performance status of ≤ 1.
• Ability to swallow oral capsules without difficulty.
• Willing and able to sign a written informed consent.

Exclusion Criteria

• More than four prior systemic therapies (not counting maintenance rituximab), except for CLL patients. Salvage therapy/conditioning regimen leading up to autologous bone marrow transplantation is considered to be one regimen (This inclusion criterion does not apply to the DLBCL-ABC cohort).
• Prior allogeneic bone marrow transplant.
• Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing.
• Major surgery within 4 weeks before first day of study drug dosing.
• CNS involvement by lymphoma.
• Active opportunistic infection or treatment for opportunistic infection within 4 weeks before first day of study drug dosing.
• History of malabsorption.
• Laboratory abnormalities:

• Creatinine > 1.5 × institutional upper limit of normal (ULN)
• Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert's syndrome)
• AST or ALT > 2.5 × institutional ULN
• Platelet count < 75,000/µL (unless patients have CLL and bone-marrow involvement, provided they are not transfusion-dependent)
• Absolute neutrophil count (ANC) < 1500/µL (unless patients have CLL and bone-marrow involvement)
• Hgb < 8.0 g/dL
• Uncontrolled illness including but not limited to: ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness that would limit compliance with study requirements.
• Risk factors for, or use of medications known to prolong QTc interval or that may be associated with Torsades de Pointes within 7 days of treatment start.
• QTc prolongation (defined as a QTc > 450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). If the screening ECG has a QTc > 450 msecs, the ECG can be submitted for a centralized, cardiologic evaluation.
• History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
• Known HIV infection.
• Hepatitis B sAg or Hepatitis C positive.
• Other medical or psychiatric illness or organ dysfunction which, in the opinion of the investigator, would either compromise the patient's safety or interfere with the evaluation of the safety of the study agent.
• Pregnant or lactating women (female patients of child-bearing potential must have a negative serum pregnancy test within 14 days of first day of drug dosing, or, if positive, a pregnancy ruled out by ultrasound).
• Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.
• History of prior cancer < 2 years ago, except for basal cell or squamous cell carcinoma of the skin, cervical cancer in situ or other in situ carcinomas.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thorsten Graef, MD, PhD

Role: STUDY_DIRECTOR

Pharmacyclics LLC.

Locations

Stanford University School of Medicine

Palo Alto, California, United States

University of Chicago

Chicago, Illinois, United States

National Cancer Institute

Bethesda, Maryland, United States

New York Prebyterian Hospital Cornell Medical Center

New York, New York, United States

Willamette Valley Cancer Institute/Research Ctr

Eugene, Oregon, United States

University of Texas, MD Anderson

Houston, Texas, United States

University of Vermont College of Medicine

Burlington, Vermont, United States

Northwest Cancer Specialists, Vancouver Cancer Center

Vancouver, Washington, United States

Yakima Valley Memorial Hospital/North Star Lodge Cancer Ctr

Yakima, Washington, United States

Countries

United States

References

Wilson WH, Young RM, Schmitz R, Yang Y, Pittaluga S, Wright G, Lih CJ, Williams PM, Shaffer AL, Gerecitano J, de Vos S, Goy A, Kenkre VP, Barr PM, Blum KA, Shustov A, Advani R, Fowler NH, Vose JM, Elstrom RL, Habermann TM, Barrientos JC, McGreivy J, Fardis M, Chang BY, Clow F, Munneke B, Moussa D, Beaupre DM, Staudt LM. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat Med. 2015 Aug;21(8):922-6. doi: 10.1038/nm.3884. Epub 2015 Jul 20.

Reference Type: DERIVED

PMID: 26193343 (View on PubMed)

Marostica E, Sukbuntherng J, Loury D, de Jong J, de Trixhe XW, Vermeulen A, De Nicolao G, O'Brien S, Byrd JC, Advani R, McGreivy J, Poggesi I. Population pharmacokinetic model of ibrutinib, a Bruton tyrosine kinase inhibitor, in patients with B cell malignancies. Cancer Chemother Pharmacol. 2015 Jan;75(1):111-21. doi: 10.1007/s00280-014-2617-3. Epub 2014 Nov 8.

Reference Type: DERIVED

PMID: 25381051 (View on PubMed)

Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8.

Reference Type: DERIVED

PMID: 23045577 (View on PubMed)

Related Links

http://www.pharmacyclics.com

Related Info

Other Identifiers

PCYC-04753

Identifier Type: -

Identifier Source: org_study_id

NCT01177878

Identifier Type: -

Identifier Source: nct_alias