Ignite Creation Date:
2025-12-24 @ 6:25 PM
Ignite Modification Date:
2025-12-29 @ 11:41 AM
Study NCT ID:
NCT05287568
Status:
RECRUITING
Last Update Posted:
2025-01-03
First Post:
2022-03-09
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
CC-486 and Venetoclax for Acute Myeloid Leukemia
Sponsor:
University of Colorado, Denver
Organization:
Study Overview
Official Title:
CC-486 and Venetoclax for Acute Myeloid Leukemia
Status:
RECRUITING
Status Verified Date:
2025-01
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 is an open label, dose escalation Phase I single institution pilot study for relapsed and refractory AML patients using CC-486 (oral azacitidine) with venetoclax. At the completion of dose escalation and after establishment of the MTD or recommended dose of CC-486 with venetoclax, an expansion phase will commence, using venetoclax with the MTD of CC-486 in relapsed/refractory patients.
Detailed Description:
Subjects confirmed eligible will be admitted to the hospital for cycle 1, day 1. Venetoclax will be administered days 1-3, with the following schema:
100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter.
Subjects taking concomitant CYP3A4 inhibitors will be given the appropriate reduced doses of venetoclax.
Subjects will be monitored inpatient for tumor lysis syndrome (TLS) for at least 24 hours after administration of the venetoclax target dose. Venetoclax will continue at 400 mg daily until day 28, the completion of cycle 1.
During dose escalation, subjects will be accrued into two cohorts using two different doses of CC-486 (cohort 1=200 mg, cohort 2=300 mg, both to be administered orally on days 1-14 of a 28-day cycle).
Two bone marrow biopsies will be performed during the first cycle: day 4 or 5 (+2 days), and day 28. The day 28 bone marrow will be used for efficacy purposes. Subsequent cycles will have response assessment bone marrow biopsies day 28 of every cycle for subjects who have not responded (CR/CRi/MLFS); after a response occurs (CR/CRi/MLFS), subjects will have bone marrow biopsies on day 28 of every 3rd cycle until they have been on the study for one year, at which point they will have a bone marrow biopsy every 6 months until study discontinuation.
Once the MTD is established, or in the absence of an MTD, a recommendation for a CC-486 dose with venetoclax is made, the study will progress to the expansion phase. For the expansion phase, 10 subjects will be recruited. These will be patients with relapsed/refractory (R/R) disease who have never received venetoclax. On day 1 of cycle 1, subjects will receive CC-486 at the MTD or recommended CC-486 dose as determined from Phase I, and this will continue daily through day 14. Venetoclax will be dose escalated, as above, from 100 to 200 to 400 mg on days 1, 2 and 3, respectively, with inpatient monitoring for TLS, and with appropriate dose reduction if administered with a CYP3A4 inhibitor. Bone marrow biopsies will occur on day 4 or 5 (+2) and on day 28 of cycle 1. Subsequent response assessment bone marrow biopsies will occur on day 28 of every 3rd cycle for subjects who have achieved a response for 1 year from study entry and then every 6 months until study discontinuation, or on day 28 of every treatment cycle for subjects who do not achieve a response.
100 mg on day 1, 200 mg on day 2, 400 mg on day 3, and it will be continued at 400mg thereafter.
Subjects taking concomitant CYP3A4 inhibitors will be given the appropriate reduced doses of venetoclax.
Subjects will be monitored inpatient for tumor lysis syndrome (TLS) for at least 24 hours after administration of the venetoclax target dose. Venetoclax will continue at 400 mg daily until day 28, the completion of cycle 1.
During dose escalation, subjects will be accrued into two cohorts using two different doses of CC-486 (cohort 1=200 mg, cohort 2=300 mg, both to be administered orally on days 1-14 of a 28-day cycle).
Two bone marrow biopsies will be performed during the first cycle: day 4 or 5 (+2 days), and day 28. The day 28 bone marrow will be used for efficacy purposes. Subsequent cycles will have response assessment bone marrow biopsies day 28 of every cycle for subjects who have not responded (CR/CRi/MLFS); after a response occurs (CR/CRi/MLFS), subjects will have bone marrow biopsies on day 28 of every 3rd cycle until they have been on the study for one year, at which point they will have a bone marrow biopsy every 6 months until study discontinuation.
Once the MTD is established, or in the absence of an MTD, a recommendation for a CC-486 dose with venetoclax is made, the study will progress to the expansion phase. For the expansion phase, 10 subjects will be recruited. These will be patients with relapsed/refractory (R/R) disease who have never received venetoclax. On day 1 of cycle 1, subjects will receive CC-486 at the MTD or recommended CC-486 dose as determined from Phase I, and this will continue daily through day 14. Venetoclax will be dose escalated, as above, from 100 to 200 to 400 mg on days 1, 2 and 3, respectively, with inpatient monitoring for TLS, and with appropriate dose reduction if administered with a CYP3A4 inhibitor. Bone marrow biopsies will occur on day 4 or 5 (+2) and on day 28 of cycle 1. Subsequent response assessment bone marrow biopsies will occur on day 28 of every 3rd cycle for subjects who have achieved a response for 1 year from study entry and then every 6 months until study discontinuation, or on day 28 of every treatment cycle for subjects who do not achieve a response.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: