Ignite Creation Date:
2024-05-05 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00103272
Status:
TERMINATED
Last Update Posted:
2013-06-04
First Post:
2005-02-07
Brief Title:
17-N-Allylamino-17-Demethoxygeldanamycin and Bortezomib in Treating Patients With Relapsed or Refractory Hematologic Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study of PS-341 Velcade Bortezomib in Combination With 17-allylamino-17-demethoxygeldanamycin 17-AAG in Patients With Relapsed or Refractory Hematologic Malignancies
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 and bortezomib in treating patients with relapsed or refractory hematologic cancer 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 Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Giving 17-N-allylamino-17-demethoxygeldanamycin together with bortezomib may kill more cancer cells
Detailed Description:
PRIMARY OBJECTIVES
I To determine the maximum tolerated dose MTD of PS-341 Velcade Bortezomib in combination with 17-allyamino-17-demethoxygeldanamycin 17-AAG in patients with relapsed or refractory acute myeloid leukemia AML or acute lymphoblastic leukemia ALL
II To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia CLL and non-Hodgkins lymphoma NHL
III To define the specific toxicities and the dose limiting toxicity DLT of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies
SECONDARY OBJECTIVES
I To determine the pharmacokinetics of 17-AAG alone and in combination with PS-341 in patients with AML ALL CLL and NHL
II To evaluate 20S proteasome inhibition following combination therapy with 17-AAG and PS-341 in patients with AML ALL CLL and NHL
III To assess the relationship between FLT3 mutational status and leukemic cell response to PS-341 and 17-AAG in patients with AML
IV To assess the relationship between Bcl-2 over-expression and response to 17-AAG and PS-341 in patients with AML and NHL
V To evaluate the effects of the combination of PS-341 and 17-AAG on Hsp90 and NF-kappaB and their downstream targets including Hsp70 Akt phosphorylated Akt p21 and caspases 3 and 9 in patient-derived primary AML and NHL cells
OUTLINE This is a dose-escalation study Patients are stratified according to diagnosis acute myeloid leukemia AML or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkins lymphoma NHL
Patients receive 17-N-allylamino-17-demethoxygeldanamycin 17-AAG intravenously IV over 1-6 hours on days 1 4 8 and 11 and bortezomib IV over 3-5 seconds on days 4 8 and 11 of course 1 and on days 1 4 8 and 11 of all subsequent courses
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit Patients achieving objective response may discontinue therapy to undergo stem cell transplantationCohorts of 3-6 patients with receive escalating doses of 17-AAG and bortezomib 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
After the MTD is determined an additional 20 patients 10 per stratum with AML or follicular NHL are enrolled and receive 17-AAG and bortezomib as above at the MTD
I To determine the maximum tolerated dose MTD of PS-341 Velcade Bortezomib in combination with 17-allyamino-17-demethoxygeldanamycin 17-AAG in patients with relapsed or refractory acute myeloid leukemia AML or acute lymphoblastic leukemia ALL
II To determine the MTD of PS-341 in combination with 17-AAG in patients with relapsed or refractory chronic lymphocytic leukemia CLL and non-Hodgkins lymphoma NHL
III To define the specific toxicities and the dose limiting toxicity DLT of PS-341 in combination with 17-AAG in the treatment of patients with relapsed or refractory hematologic malignancies
SECONDARY OBJECTIVES
I To determine the pharmacokinetics of 17-AAG alone and in combination with PS-341 in patients with AML ALL CLL and NHL
II To evaluate 20S proteasome inhibition following combination therapy with 17-AAG and PS-341 in patients with AML ALL CLL and NHL
III To assess the relationship between FLT3 mutational status and leukemic cell response to PS-341 and 17-AAG in patients with AML
IV To assess the relationship between Bcl-2 over-expression and response to 17-AAG and PS-341 in patients with AML and NHL
V To evaluate the effects of the combination of PS-341 and 17-AAG on Hsp90 and NF-kappaB and their downstream targets including Hsp70 Akt phosphorylated Akt p21 and caspases 3 and 9 in patient-derived primary AML and NHL cells
OUTLINE This is a dose-escalation study Patients are stratified according to diagnosis acute myeloid leukemia AML or acute lymphoblastic leukemia vs chronic lymphoctyic leukemia or non-Hodgkins lymphoma NHL
Patients receive 17-N-allylamino-17-demethoxygeldanamycin 17-AAG intravenously IV over 1-6 hours on days 1 4 8 and 11 and bortezomib IV over 3-5 seconds on days 4 8 and 11 of course 1 and on days 1 4 8 and 11 of all subsequent courses
Treatment repeats every 21 days for 3-12 courses provided patient is receiving clinical benefit Patients achieving objective response may discontinue therapy to undergo stem cell transplantationCohorts of 3-6 patients with receive escalating doses of 17-AAG and bortezomib 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
After the MTD is determined an additional 20 patients 10 per stratum with AML or follicular NHL are enrolled and receive 17-AAG and bortezomib as above at the MTD
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 0448 | None | None | None |
| NCI-6520 | None | None | None |
| CDR0000409584 | None | None | None |
| OSU-2004C0084 | None | None | None |
| OSU-0448 | None | None | None |
| U01CA076576 | NIH | None | httpsreporternihgovquickSearchU01CA076576 |