Study of Carfilzomib in Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL) or Prolymphocytic Leukemia (PLL)

Summary

RATIONALE:

Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

PURPOSE:

This phase I trial is studying the side effects and the best dose of carfilzomib in treating patients with relapsed or refractory chronic lymphocytic leukemia(CLL),small lymphocytic lymphoma(SLL), or prolymphocytic leukemia (PLL).

Conditions

• B-cell Chronic Lymphocytic Leukemia
• Hematopoietic/Lymphoid Cancer
• Prolymphocytic Leukemia
• Recurrent Small Lymphocytic Lymphoma
• Refractory Chronic Lymphocytic Leukemia

Interventions

DRUG

carfilzomib

Given IV infusion lasting 30 minutes. Will be administered IV at a specified dose in mg/m2 QDx2 weekly for 3 weeks (days 1, 2, 8, 9, 15, and 16). The first and second dose will always be administered at 20 mg/m2.

OTHER

Cytokine Assessment

TNF-α,IFN-γ,IL-6,IL-8,IL-10,and IL-1β pre-dose, completion, 30 minutes, 2 hours, 6 hours, and approximately 24 hours from initiation of therapy on days 1 and 8 of treatment. These will be assessed utilizing standard ELISA or flow cytometry methodology. Other cytokines or soluble factors may be assessed that relate to drug toxicity or response. After 6 patients are examined in each group, the time points or number of cytokines examined may be changed to decrease time points examined. Cytokines will be examined by a multiplex flow cytometry assay or ELISA. Other cytokines, chemokines, or soluble factors may be assessed on residual material not used for these studies.

OTHER

Pharmacodynamic Studies

Based upon our preliminary data changes occuring in vivo during carfilzomib treatment will be determined and if their occurrence correlates with both clinical response and development of cytokine release. These studies will be performed from CD19 selected CLL cells at screening, pre-treatment, 4 hours, and 24 hours post-therapy on days 1 and 8 of treatment; end of therapy evaluation, and at time of relapse (in responding patients). These studies will include assessment of NF-κB (p50/p65 binding; I-κB level, P-I-κB level, select target genes), p53 (p53 nuclear levels, p53 nuclear binding, and select target genes), p73, and ER stress response. Standard Western Blot, EMSA, RT-PCR will be done to complete these studies.

OTHER

Proteosome Inhibition Assessment

Proteosome inhibition on CLL cells will be examined at screening, pre-treatment and post-treatment (immediately after completion of drug) days 1, pre-treatment day 2, day 3 (optional), day 5 (optional),pre and post-treatment days 8, pre and post-treatment days 9, day 10 (optional),day 12 (optional), and day 15 (optional).

OTHER

Pharmacogenomic Studies

Germ line DNA from a buccal swab and bone marrow fibroblasts will be obtained at baseline screening for possible examination of SNP polymorphisms that may correlate with response and toxicity to carfilzomib therapy. Tumor DNA will be derived from samples obtained at baseline for the p53 mutational studies. SNPs related to drug metabolism, response, or toxicity to therapy, cytokine release, and tumor biology may be examined. Other SNPs may be used in the future. Given the potential for contamination in the recipient, recipient DNA from a buccal swab and/or saliva will be obtained at baseline screening for examination of SNP polymorphisms that may correlate with response, toxicity, and pharmacokinetics.

Sponsors & Collaborators

• Amgen

  collaborator INDUSTRY

• Ohio State University Comprehensive Cancer Center

  lead OTHER

Principal Investigators

• Jennifer Woyach, MD · Ohio State University Comprehensive Cancer Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-10-31

Primary Completion

2014-07-31

Completion

2015-09-30

Countries

• United States

Study Locations