Ignite Creation Date:
2024-05-05 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00004862
Status:
COMPLETED
Last Update Posted:
2013-02-01
First Post:
2000-03-07
Brief Title:
Augmerosen Plus Fludarabine and Cytarabine in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Phase I Study of G3139 NSC 683428 in Combination With Salvage Chemotherapy for Treatment of Refractory and Relapsed Acute Myeloid Leukemia AML and Acute Lymphoblastic Leukemia ALL
Status:
COMPLETED
Status Verified Date:
2002-05
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:
Phase I trial to study the effectiveness of augmerosen plus fludarabine and cytarabine in treating patients who have refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die Gene therapy such as augmerosen may make cancer cells more sensitive to chemotherapy drugs Combining more than one drug with augmerosen may kill more cancer cells
Detailed Description:
OBJECTIVES
I Determine the maximum tolerated dose of fludarabine and cytarabine when combined with augmerosen G3139 in patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia and recommend a starting dose for phase II studies
II Determine the qualitative and quantitative toxic effects of this regimen in these patients with regard to organ specificity time course predictability and reversibility
III Document the therapeutic response in patients treated with this regimen IV Measure bcl-2 and related antiapoptotic and proapoptotic proteins in circulating andor marrow leukemia cells before during and after treatment with G3139
V Measure WT1 expression in leukemic blasts as a surrogate marker for minimal residual disease and correlate it with bcl-2 and related antiapoptotic and proapoptotic gene expression
VI Determine the time required for bcl-2 levels to recover after treatment with this regimen
VII Determine if TP53 mutations are present in leukemic blasts and how these mutations may affect expression of BAX level of treatment induced apoptosis and clinical endpoints
VIII Assess apoptosis in leukemic cells before during and after treatment with this regimen
IX Determine the pharmacokinetics of fludarabine and cytarabine in patients treated with this regimen
X Perform pharmacodynamic studies of fludarabine and cytarabine on the leukemic cells of patients prior to treatment
OUTLINE This is a dose-escalation study of fludarabine and cytarabine
Patients receive augmerosen IV continuously on days 1-10 and filgrastim G-CSF subcutaneously beginning on day 5 and continuing until blood counts recover Patients receive fludarabine IV over 30 minutes followed 35 hours later by cytarabine IV over 4 hours on days 6-10 Patients who achieve complete response CR receive a second course beginning 4 weeks after completion of the first course Patients who achieve CR and have a matched sibling or unrelated bone marrow donor may undergo allogeneic bone marrow transplantation Cohorts of 3-6 patients receive escalating doses of fludarabine and cytarabine until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
I Determine the maximum tolerated dose of fludarabine and cytarabine when combined with augmerosen G3139 in patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia and recommend a starting dose for phase II studies
II Determine the qualitative and quantitative toxic effects of this regimen in these patients with regard to organ specificity time course predictability and reversibility
III Document the therapeutic response in patients treated with this regimen IV Measure bcl-2 and related antiapoptotic and proapoptotic proteins in circulating andor marrow leukemia cells before during and after treatment with G3139
V Measure WT1 expression in leukemic blasts as a surrogate marker for minimal residual disease and correlate it with bcl-2 and related antiapoptotic and proapoptotic gene expression
VI Determine the time required for bcl-2 levels to recover after treatment with this regimen
VII Determine if TP53 mutations are present in leukemic blasts and how these mutations may affect expression of BAX level of treatment induced apoptosis and clinical endpoints
VIII Assess apoptosis in leukemic cells before during and after treatment with this regimen
IX Determine the pharmacokinetics of fludarabine and cytarabine in patients treated with this regimen
X Perform pharmacodynamic studies of fludarabine and cytarabine on the leukemic cells of patients prior to treatment
OUTLINE This is a dose-escalation study of fludarabine and cytarabine
Patients receive augmerosen IV continuously on days 1-10 and filgrastim G-CSF subcutaneously beginning on day 5 and continuing until blood counts recover Patients receive fludarabine IV over 30 minutes followed 35 hours later by cytarabine IV over 4 hours on days 6-10 Patients who achieve complete response CR receive a second course beginning 4 weeks after completion of the first course Patients who achieve CR and have a matched sibling or unrelated bone marrow donor may undergo allogeneic bone marrow transplantation Cohorts of 3-6 patients receive escalating doses of fludarabine and cytarabine until the maximum tolerated dose MTD is determined The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity
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-99H0257 | None | None | None |
| OSU-9977 | None | None | None |
| NCI-T99-0057 | None | None | None |
| CDR0000067515 | REGISTRY | PDQ Physician Data Query | None |