Efficacy and Safety Study of PCI-32765 Combine With Ofatumumab in CLL (PCYC-1109-CA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Ohio State University
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01217749
First received: October 7, 2010
Last updated: July 3, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine the efficacy and safety of a fixed-dose, daily regimen of orally administered PCI-32765 combined with ofatumumab in subjects with relapsed/refractory CLL/SLL and related diseases


Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Diffuse Well-Differentiated Lymphocytic Lymphoma
Prolymphocyctic Leukemia
Richter's Transformation
Drug: PCI-32765
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Phase 1b/2, Safety and Efficacy Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, and Ofatumumab in Subjects With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Prolymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by Pharmacyclics:

Primary Outcome Measures:
  • Response and safety of PCI-32765 [ Time Frame: At the end of cycles 1 and 3 ] [ Designated as safety issue: Yes ]
    Response rate as defined by recent guidelines in Chronic Lymphocytic Leukemia


Secondary Outcome Measures:
  • Safety [ Time Frame: 3 yrs ] [ Designated as safety issue: Yes ]
    Safety including incidence of adverse events requiring dose delay or discontinuation of PCI-32765, incidence of Grade ≥3 adverse events (AEs) and incidence of serious adverse events (SAEs).

  • Time to Best Response [ Time Frame: at the end of Cycles 1,3 and 6 (28 days for each cycle) ] [ Designated as safety issue: No ]
    Overall response rate as defined by recent guidelines on CLL


Estimated Enrollment: 71
Study Start Date: December 2010
Estimated Study Completion Date: September 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PCI-32765 Drug: PCI-32765
420 mg daily

  Eligibility

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

Inclusion Criteria:

  • Subjects with histologically confirmed chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), prolymphocytic leukemia (PLL) as defined by WHO classification of hematopoietic neoplasms, or Richter's transformation arising out of CLL/SLL and satisfying ≥ 1 of the following conditions:
  • 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 degree 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
  • Need for cytoreduction prior to stem cell transplant
  • Subjects must have failed ≥ 2 prior therapies for CLL including a nucleoside analog or ≥ 2 prior therapies not including nucleoside analog if there is a contraindication to such therapy

    •> 10% expression of CD20 on tumor cells

  • ECOG performance status ≤ 2
  • Life expectancy ≥ 12 weeks
  • Subjects must have organ and marrow function as defined below:

Absolute neutrophil count (ANC) ≥ 1000/µL in the absence of bone marrow involvement Platelets ≥ 30,000/μL Total bilirubin ≤ 1.5 x institutional upper limit of normal unless due to Gilbert's disease AST(SGOT) ≤ 2.5 x institutional upper limit of normal unless due to infiltration of the liver Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 50 mL/min

  • No history of prior anaphylactic reaction to rituximab
  • No history of prior exposure to ofatumumab
  • Age ≥ 18 years
  • Body weight ≥ 40 kg

Exclusion Criteria:

  • A 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
  • Significant cardiovascular disease
  • Any condition which could interfere with the absorption or metabolism of PCI-32765 including unable to swallow capsules, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  • Known history of Human Immunodeficiency Virus (HIV) or active infection with Hepatitis C Virus (HCV) or Hepatitis B Virus (HBV) or any uncontrolled active systemic infection
  • Any anticancer immunotherapy, chemotherapy, radiotherapy, or experimental therapy within 4 weeks before first dose of study drug. Corticosteroids for disease-related symptoms are allowed provided 1 week washout occurs.
  • Active central nervous system (CNS) involvement by lymphoma
  • Major surgery within 4 weeks before first dose of study drug
  • Lactating or pregnant
  • Known moderate to severe chronic obstructive pulmonary disease (COPD)
  • History of prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for at least 2 years or which will not limit survival to < 2 years
  • History of Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01217749

Locations
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Pharmacyclics
Ohio State University
Investigators
Principal Investigator: Samantha Jaglowski, MD Ohio State University
  More Information

Additional Information:
No publications provided by Pharmacyclics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pharmacyclics
ClinicalTrials.gov Identifier: NCT01217749     History of Changes
Other Study ID Numbers: PCYC-1109-CA, PCI-32765
Study First Received: October 7, 2010
Last Updated: July 3, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Prolymphocytic
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 21, 2014