Ignite Creation Date:
2025-12-24 @ 9:44 PM
Ignite Modification Date:
2026-02-22 @ 7:04 AM
Study NCT ID:
NCT03194932
Status:
COMPLETED
Last Update Posted:
2023-02-14
First Post:
2017-06-19
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Leukemia of Ambiguous Lineage
Sponsor:
St. Jude Children's Research Hospital
Organization:
Study Overview
Official Title:
A Phase I and Expansion Cohort Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The purpose of this study is to test the safety and determine the best dose of venetoclax and cytarabine when given with or without idarubicin in treating pediatric patients with acute myeloid leukemia (AML) that did not respond to treatment (refractory) or has come back after treatment (relapsed).
PRIMARY OBJECTIVE: Determine a tolerable combination of venetoclax plus chemotherapy in pediatric patients with relapsed or refractory AML or acute leukemia of ambiguous lineage. The primary endpoints are the recommended phase 2 doses (RP2D) of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin.
SECONDARY OBJECTIVE: Estimate the overall response rate to the combination of venetoclax and chemotherapy in pediatric patients with relapsed or refractor AML or acute leukemia of ambiguous lineage. The secondary endpoints are the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated at the RP2D.
PRIMARY OBJECTIVE: Determine a tolerable combination of venetoclax plus chemotherapy in pediatric patients with relapsed or refractory AML or acute leukemia of ambiguous lineage. The primary endpoints are the recommended phase 2 doses (RP2D) of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin.
SECONDARY OBJECTIVE: Estimate the overall response rate to the combination of venetoclax and chemotherapy in pediatric patients with relapsed or refractor AML or acute leukemia of ambiguous lineage. The secondary endpoints are the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated at the RP2D.
Detailed Description:
This study will be done in two parts:
* Part 1 - Dose Escalation: The goal of Part 1 of the study is to find the highest tolerable combination and recommended phase 2 doses (RP2D) of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin that can be given to patients with leukemia.
* Part 2 - Dose Expansion: After determination of doses in Part 1, patients will be enrolled on Part 2 to look at the effects of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin.
Depending on when participants enroll on the study, Part 1 participants will receive one of the following courses of therapy:
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-17; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-11; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-11; idarubicin once on day 8; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-17; idarubicin once on day 8.
Part 2 participants will receive one of the following courses of therapy:
* Venetoclax daily on days 1-28; cytarabine - to be determined from Part 1 of the study; OR
* Venetoclax daily on days 1-28; cytarabine - to be determined from Part 1 of the study; idarubicin once on day 8.
The cytarabine dosage will be that found in Part 1 to be the highest safest dose.
Those participants receiving idarubicin will also receive dexrazoxane.
Note: Part 1 has been completed. Part 2 participants receive the following determined from Part 1 of the study:
* Venetoclax daily on days 1-28; cytarabine every 12 hours days 8-11 OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours days 8-11; idarubicin once on day 8.
All participants on both Part 1 and Part 2 receive one intrathecal (IT) chemotherapy before starting the first cycle. Patients with CNS disease will receive weekly IT therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Bone marrow aspiration and biopsy to assess response will be performed between days 28 and 42 of cycle 1. Patients who achieve complete remission/complete remission with incomplete count recovery/partial remission (CR/CRi/PR) and who do not experience unacceptable toxicity during cycle 1 may receive up to four cycles of chemotherapy.
Cohort C (Amendment 5.0): Treatment of participants enrolled in cohort C will include: Venetoclax daily on days 1-21; cytarabine every 12 hours days 8-11; azacytidine days 1-7. Participants will receive one intrathecal (IT) chemotherapy before starting the first cycle. Participants with CNS disease will receive weekly ITMHA until the cerebrospinal fluid becomes free of leukemia.
The rolling-6 design will be used to determine the safety of cohort C. After cohort C is deemed to be safe, additional patients will be enrolled, if necessary, so that at least 6 patients are treated in cohort C to confirm tolerability. After tolerability is confirmed, 6 additional patients will be treated to explore activity.
* Part 1 - Dose Escalation: The goal of Part 1 of the study is to find the highest tolerable combination and recommended phase 2 doses (RP2D) of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin that can be given to patients with leukemia.
* Part 2 - Dose Expansion: After determination of doses in Part 1, patients will be enrolled on Part 2 to look at the effects of venetoclax plus cytarabine and venetoclax plus cytarabine and idarubicin.
Depending on when participants enroll on the study, Part 1 participants will receive one of the following courses of therapy:
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-17; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-11; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-11; idarubicin once on day 8; OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours on days 8-17; idarubicin once on day 8.
Part 2 participants will receive one of the following courses of therapy:
* Venetoclax daily on days 1-28; cytarabine - to be determined from Part 1 of the study; OR
* Venetoclax daily on days 1-28; cytarabine - to be determined from Part 1 of the study; idarubicin once on day 8.
The cytarabine dosage will be that found in Part 1 to be the highest safest dose.
Those participants receiving idarubicin will also receive dexrazoxane.
Note: Part 1 has been completed. Part 2 participants receive the following determined from Part 1 of the study:
* Venetoclax daily on days 1-28; cytarabine every 12 hours days 8-11 OR
* Venetoclax daily on days 1-28; cytarabine every 12 hours days 8-11; idarubicin once on day 8.
All participants on both Part 1 and Part 2 receive one intrathecal (IT) chemotherapy before starting the first cycle. Patients with CNS disease will receive weekly IT therapy until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses). Bone marrow aspiration and biopsy to assess response will be performed between days 28 and 42 of cycle 1. Patients who achieve complete remission/complete remission with incomplete count recovery/partial remission (CR/CRi/PR) and who do not experience unacceptable toxicity during cycle 1 may receive up to four cycles of chemotherapy.
Cohort C (Amendment 5.0): Treatment of participants enrolled in cohort C will include: Venetoclax daily on days 1-21; cytarabine every 12 hours days 8-11; azacytidine days 1-7. Participants will receive one intrathecal (IT) chemotherapy before starting the first cycle. Participants with CNS disease will receive weekly ITMHA until the cerebrospinal fluid becomes free of leukemia.
The rolling-6 design will be used to determine the safety of cohort C. After cohort C is deemed to be safe, additional patients will be enrolled, if necessary, so that at least 6 patients are treated in cohort C to confirm tolerability. After tolerability is confirmed, 6 additional patients will be treated to explore activity.
Study Oversight
Has Oversight DMC:
False
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?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2017-01129 | REGISTRY | NCI Clinical Trial Registration Program | View |