Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00098488
Status:
TERMINATED
Last Update Posted:
2013-06-04
First Post:
2004-12-07
Brief Title:
17-N-Allylamino-17-Demethoxygeldanamycin With or Without Rituximab in Treating Patients With Relapsed B-Cell Chronic Lymphocytic Leukemia or Prolymphocytic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase 1 Study of 17-allylamino-17-demethoxygeldanamycin 17-AAG NSC 330507 IND 57966 and Rituximab in Patients With Relapsed B-cell Chronic Lymphocytic Leukemia CLL
Status:
TERMINATED
Status Verified Date:
2013-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Description:
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 v30 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 PDK1AKT-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 progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease Patients failing to achieve a 25 reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1 4 8 11 15 18 and 22 and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4 8 15 and 22 in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of 17-AAG as a single agent or in combination with rituximab until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Patients are followed up at 2 months and then every 3 months for 2 years
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 v30 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 PDK1AKT-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 progression or unacceptable toxicity and provided absolute lymphocyte count continues to decrease Patients failing to achieve a 25 reduction in measurable disease after course 1 OR with disease progression after courses 1 or 2 of single-agent 17-AAG proceed to combination therapy comprising 17-AAG IV over 2 hours on days 1 4 8 11 15 18 and 22 and rituximab IV over 4 hours on days 1 and 2 and over 1 hour on days 4 8 15 and 22 in the absence of disease progression or unacceptable toxicity
Cohorts of 3-6 patients receive escalating doses of 17-AAG as a single agent or in combination with rituximab until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity
Patients are followed up at 2 months and then every 3 months for 2 years
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| OSU 0429 | None | None | None |
| 2004C0058 | None | None | None |
| NCI-6518 | None | None | None |
| OSU-0429 | None | None | None |
| CDR0000401516 | None | None | None |
| R21CA115048 | NIH | None | httpsreporternihgovquickSearchR21CA115048 |