Study of Venetoclax in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Leukemia of Ambiguous Lineage
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03194932|
Recruitment Status : Recruiting
First Posted : June 21, 2017
Last Update Posted : June 19, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Venetoclax Drug: Cytarabine Drug: Idarubicin Drug: Intrathecal Triple Therapy||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||54 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Participants receive venetoclax plus cytarabine alone or combination chemotherapy of cytarabine plus idarubicin.|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||July 11, 2017|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||August 2020|
In Part 1, venetoclax with cytarabine will initially be given at dose level 1 and escalated based on tolerability. Idarubicin will be given only at dose level 4.
Note: Part 1 has been completed.
Two expansion cohorts will be enrolled:
Intrathecal Triple Therapy (ITMHA) will be given prior to cycle 1. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly ITMHA beginning on day 8 until the cerebrospinal fluid becomes free of leukemia.
Venetoclax will be given as oral tablets, which are intended to be swallowed intact and may not to be crushed or otherwise altered for administration, or as an oral suspension for patients who cannot swallow tablets.
Given intravenously (IV) or intrathecally (IT).
Other Name: Idamycin PFS
Drug: Intrathecal Triple Therapy
- Maximum tolerated combination (MTC) [ Time Frame: 28 days after start of therapy ]The MTC will be the highest intensity level at which six participants have been treated, with at most one participant experiencing an intensity-limiting toxicity.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03194932
|Contact: Jeffrey E. Rubnitz, MD, PhDfirstname.lastname@example.org|
|United States, California|
|Children's Hospital of Orange County||Recruiting|
|Orange, California, United States, 92868|
|Contact: Jamie Frediani, MD 714-509-8636 email@example.com|
|Principal Investigator: Jamie Frediani, MD|
|Lucille Packard Children's Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Norman J. Lacayo, MD 650-497-8953 firstname.lastname@example.org|
|Principal Investigator: Norman J. Lacayo, MD|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Thomas B. Alexander, MD 877-668-0683 email@example.com|
|Principal Investigator: Thomas B. Alexander, MD|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Jeffrey E Rubnitz, MD, PhD 866-278-5833 firstname.lastname@example.org|
|Principal Investigator: Jeffrey E Rubnitz, MD, PhD|
|Principal Investigator:||Jeffrey E. Rubnitz, MD, PhD||St. Jude Children's Research Hospital|