Clinical Trial: 17-N-Allylamino-17-Demethoxygeldanamycin With or Without Rituximab in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase 1 Study of 17-allylamino-17-demethoxygeldanamycin (17-AAG) (NSC 330507; IND 57,966) and Rituximab in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia (CLL)

Brief Summary: This phase I trial is studying the side effects and best dose of 17-N-allylamino-17-demethoxygeldanamycin when given with or without rituximab in treating patients with relapsed B-cell chronic lymphocytic leukemia or prolymphocytic leukemia. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Monoclonal antibodies may kill cancer cells that are left after chemotherapy. Giving 17-N-allylamino-17-demethoxygeldanamycin with or without rituximab may kill more cancer cells.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) of twice weekly 17-allylamino-17-demethoxygeldanamycin (17-AAG) in combination with weekly rituximab in patients with relapsed chronic lymphocytic leukemia (CLL).

II. To examine the pharmacology of twice weekly 17-AAG in combination with weekly rituximab in patients with relapsed CLL.

SECONDARY OBJECTIVES:

I. To evaluate toxicity (using NCI CTCAE v3.0 criteria) and preliminary efficacy of twice weekly 17-AAG when used in combination with weekly rituximab in this patient population.

II. To examine the kinetics of depletion of PDK1/AKT-related proteins, mutant p53 and up-regulation of alternative targets that mediate resistance to therapy following treatment with twice weekly 17-AAG; and the relationship of this to spontaneous and drug-induced apoptosis in patients with relapsed CLL.

III. To examine the immunologic effects of twice weekly 17-AAG, in conjunction with weekly rituximab, in patients with relapsed CLL.

IV. To evaluate toxicity and preliminary efficacy of twice weekly 17-AAG as a single agent in this patient population.

OUTLINE: This is a multicenter, dose-escalation study of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG).

Patients receive 17-AAG intravenously (IV) over 2 hours on days 1, 4, 8, 11, 15 and 18 (course 1). Patients achieving ≥ 25% reduction in measurable disease after course 1 receive an additional course of single-agent 17-AAG approximately 10 days later in the absence of disease
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Maximum tolerated dose (MTD) of 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) [ Time Frame: Week 4 ]

Defined at the dose level of 17-AAG at which 2 (or more) of 6 patients develop dose-limiting toxicity (DLT).


Original Primary Outcome:

Current Secondary Outcome: Minimally effective pharmacological dose (MEPD) of 17-AAG based on down-modulation of the target protein Akt [ Time Frame: Day 1 ]

Defined as the 17-AAG dose achieving >= 50% reduction in Akt protein expression.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 7, 2004
Date Started: April 2005
Date Completion:
Last Updated: June 3, 2013
Last Verified: June 2013