Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 16 of 71 for:    Venetoclax AND Acute Myeloid Leukemia

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
Sponsor:
Collaborator:
Gateway for Cancer Research
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

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.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Venetoclax Drug: Cytarabine Drug: Idarubicin Drug: Intrathecal Triple Therapy Phase 1

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.


Layout table for study information
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)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Treatment

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:

  • Cohort A will be a group of 12 participants receiving the recommended phase 2 doses (RP2D) of venetoclax plus cytarabine.
  • Cohort B will be a group of 12 participants receiving the RP2D of venetoclax plus cytarabine and idarubicin.

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.

Drug: Venetoclax
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.
Other Names:
  • Venclextra®
  • ABT-199

Drug: Cytarabine
Given intravenously (IV) or intrathecally (IT).
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar®

Drug: Idarubicin
Given IV.
Other Name: Idamycin PFS

Drug: Intrathecal Triple Therapy
Given IT.
Other Names:
  • ITMHA
  • methotrexate/hydrocortisone/cytarabine




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have a diagnosis of AML or acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype a cute leukemia) and meet the criteria below:

    • Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy, OR
    • Early relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission and within one year of diagnosis, OR
    • Relapsed leukemia that is refractory to at least one course of salvage therapy (i.e., therapy given after the relapse has occurred), OR
    • Second or greater relapse
    • Patients with late relapses, defined as the re-appearance of leukemia after the achievement of remission and greater than one year from diagnosis, may be enrolled in the dose expansion portion of the study only.
    • Patients in all categories above must have ≥ 5% blasts in the bone marrow as assessed by morphology or > 1 blasts in the bone marrow as assessed by flow cytometry. However, if an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia with ≥ 5% blasts in the peripheral blood. In addition, patients in all categories must not be eligible to undergo curative therapy, such as immediate SCT, because of disease burden, time needed to identify a stem cell donor, or other reasons.
  • Adequate organ function defined as the following:

    • Direct bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    • AST (SGOT) and ALT (SGPT) ≤ 4 x ULN
    • Normal creatinine for age or a calculated creatinine clearance ≥ 60 mL/min/1.73 m2
    • Left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25%
  • St. Jude patients must be between 2 years and ≤ 21 years of age, on therapy (active patient), or within 3 years of completion of therapy. Patients treated at collaborating sites must be ≤ 24 years old.
  • Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.
  • Patients must have fully recovered from the acute effects of all prior therapy and cannot have evidence of graft-versus-host disease (GVHD)

Exclusion Criteria:

  • Must not be pregnant or breastfeeding. Male or female of reproductive potential must agree to use effective contraception for the duration of study participation.
  • Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
  • Uncontrolled infection. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
  • Impairment of GI function or GI disease that may significantly alter the absorption of venetoclax.

Information from the National Library of Medicine

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


Contacts
Layout table for location contacts
Contact: Jeffrey E. Rubnitz, MD, PhD 866-278-5833 referralinfo@stjude.org

Locations
Layout table for location information
United States, California
Children's Hospital of Orange County Recruiting
Orange, California, United States, 92868
Contact: Jamie Frediani, MD    714-509-8636    jfrediani@choc.org   
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    lacayon@stanford.edu   
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    talex@email.unc.edu   
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    info@stjude.org   
Principal Investigator: Jeffrey E Rubnitz, MD, PhD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Gateway for Cancer Research
Investigators
Layout table for investigator information
Principal Investigator: Jeffrey E. Rubnitz, MD, PhD St. Jude Children's Research Hospital

Additional Information:
Layout table for additonal information
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03194932     History of Changes
Other Study ID Numbers: VENAML
NCI-2017-01129 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: June 21, 2017    Key Record Dates
Last Update Posted: June 19, 2019
Last Verified: June 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Venetoclax
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Antiviral Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors