Phase I Dose-Escalation Study of Bruton’s Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Recurrent B Cell Lymphoma
The goal of this clinical research study is to find the highest tolerable dose of PCI-32765 that can be given to patients with recurrent B-cell lymphoma.
Disease Group: Lymphoma
Treatment Agent: PCI-32765
Treatment Location: Both at MD Anderson & outside MD Anderson at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: N/A
Sponsor: Pharmacyclics, Inc.
Return Visit: At the beginning of each cycle, then every 2-3 months until the participant has disease progression for a maximum of 6 months.
Home Care: The study drug will be taken at home.
Primary Objectives Establish the safety and the maximum tolerated dose (MTD) of orally administered PCI-32765 in patients with recurrent B cell lymphoma. Determine pharmacokinetics (PK) of orally administered PCI-32765 Measure pharmacodynamic (PD) parameters to include drug occupancy of Btk, the target enzyme, and effect on biological markers of B cell function Secondary Objective Evaluate tumor responses
IRB Review and Approval Date: 10/21/2008
Recruitment Status: Not Accepting
Projected Accrual: 52
1) Women and men >/= 18 years of age. There is no experience with
this drug in a pediatric population.
2) Body weight >/= 40 kg.
3) Recurrent surface immunoglobulin positive B cell non-Hodgkin’s lymphoma NHL according to WHO classificationincluding small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) and lymphoplasmacytic lymphoma, including Waldenstrom's Macroglobulinemia (WM)..
4) Measurable disease (for NHL bi-dimensional disease >= 2 cm diameter in at least on dimension, for CLL >= 5000 leukemia cells/mm3, and for WM presence of immunoglobulin M paraprotein with a minimum IgM level >= 1000 mg/dL and infiltration of bone marrow by lymphoplasmacytic cells).
5) 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.
6) ECOG performance status of </= 1.
7) Ability to swallow oral capsules without difficulty.
8) Willing and able to sign a written informed consent.
1) 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
2) Prior allogeneic bone marrow transplant.
3) Immunotherapy, chemotherapy, radiotherapy or experimental therapy within 4 weeks before first day of study drug dosing.
4) Major surgery within 4 weeks before first day of study drug dosing.
5) CNS involvement by lymphoma.
6) Active opportunistic infection or treatment for opportunistic infection within 4 weeks before first day of study drug dosing.
7) History of malabsorption.
8) Laboratory abnormalities: a.) Creatinine > 1.5 × institutional upper limit of normal (ULN) b.) Total bilirubin > 1.5 x institutional ULN (unless elevated from documented Gilbert’s syndrome) c.) AST or ALT > 2.5 × institutional ULN d.) Platelet count < 75,000/microL, unless patients have CLL and bone marrow involvement, provided they are not transfusion-dependent e.) Absolute neutrophil count (ANC) < 1500/microL unless patients have CLL and bone marrow involvement f.) Hgb < 8.0 g/dL
9) 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.
10) 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.
11) 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.
12) History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within the past 6 months.
13) Known HIV infection.
14) Hepatitis B sAg or Hepatitis C positive.
15) 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.
16) 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).
17) Women of child-bearing potential or sexually active men, unwilling to use adequate contraceptive protection during the course of the study.
18) 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.
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