Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)
NCT ID: NCT05183035
Last Updated: 2026-01-13
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE3
98 participants
INTERVENTIONAL
2022-10-01
2031-04-30
Brief Summary
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Detailed Description
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This is a trial for children, adolescents and young adults with 2nd relapsed AML or 1st relapsed AML unable to receive additional anthracycline.
This is randomized trial of venetoclax in combination with intensive chemotherapy (fludarabine/cytarabine/gemtuzumab ozogamicin) for the first two cycles (42-day-cycles) that would inform and evaluate if this agent is an effective option for this population to improve its poor prognosis. Participants can receive up to two cycles of induction chemotherapy before hematopoietic stem cell transplantation (HSCT). If participants who have perceived clinical benefit cannot be transplanted after the 2 cycles, maintenance treatment may be given at the discretion of the investigator. In Arm B (experimental arm), participants can continue venetoclax if they have perceived clinical benefit, and maintenance therapy will combine venetoclax with azacitidine for a maximum of 24 cycles. In Arm A (control arm), participants will receive azacitidine in monotherapy. Maintenance is continued until clinical progression or unacceptable toxicity with a maximum of 24 cycles.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Arm A: Control Arm without Venetoclax
During Cycle 1 (42-day-cycles), participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. Gemtuzumab 3 mg/m\^2 will be given on Day 6 (only for participants with CD33 expression on leukemia blasts).
During Cycle 2 participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. After Cycle 2 participants are assessed for HSCT or azacitidine maintenance therapy.
Fludarabine
Intravenous (IV) infusion
Cytarabine
Intravenous (IV) infusion
Gemtuzumab Ozogamicin
Intravenous (IV) infusion
Azacitidine
Intravenous (IV) infusion or subcutaneous injection
Arm B: Experimental Arm with Venetoclax
During Cycle 1 (42-day-cycles), participants will receive 300 mg adult dose equivalent of venetoclax once on Day 1 followed by 600 mg adult dose equivalent of venetoclax on Days 2-21. Participants will also receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 8-12. Gemtuzumab 3 mg/m\^2 will be given on Day 13 (only for participants with CD33 expression on leukemia blasts).
During Cycle 2, participants will receive 600 mg adult dose equivalent of venetoclax on Days 1-21. Participants will receive 30 mg/m\^2 of fludarabine followed by 2 g/m\^2 of cytarabine on Days 1-5. After Cycle 2 participants are assessed for HSCT or azacitidine maintenance therapy in combination with venetoclax.
Fludarabine
Intravenous (IV) infusion
Cytarabine
Intravenous (IV) infusion
Gemtuzumab Ozogamicin
Intravenous (IV) infusion
Azacitidine
Intravenous (IV) infusion or subcutaneous injection
Venetoclax
Orally via tablet or powder suspension
Interventions
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Fludarabine
Intravenous (IV) infusion
Cytarabine
Intravenous (IV) infusion
Gemtuzumab Ozogamicin
Intravenous (IV) infusion
Azacitidine
Intravenous (IV) infusion or subcutaneous injection
Venetoclax
Orally via tablet or powder suspension
Eligibility Criteria
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Inclusion Criteria
* Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
* Participants must have one of the following:
1. Children, adolescents, and young adults with AML without demonstrated FLT3/internal tandem duplication (ITD) mutation. Ideally, the status of the mutation needs to be proven in the current relapse. Nevertheless, patients with previous FLT3/ITD negative test from prior lines can be included based on local results in order to not delay the start of treatment.
2. And participants must have AML which is either:
* Untreated second relapse, in participants who are sufficiently fit to undergo another round of intensive chemotherapy, or
* Untreated first relapse, in participants who cannot tolerate additional anthracycline containing chemotherapy per investigator discretion.
* Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score).
* Participants must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to start of protocol treatment:
1. Cytotoxic chemotherapy: Must not have received cytotoxic chemotherapy within 14 days prior to start of protocol treatment, except for corticosteroids, low dose cytarabine or hydroxyurea that can be given up to 24 hours prior to start of protocol treatment.
2. Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
3. Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate before start of protocol treatment. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before start of protocol treatment. Any toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
4. Interleukins, Interferons and Cytokines (other than Hematopoietic Growth Factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than Hematopoietic Growth Factors) before start of protocol treatment.
5. Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor before start of protocol treatment.
6. Radiation therapy (RT) (before start of protocol treatment):
* ≥ 14 days have elapsed for local palliative RT (small port);
* ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis;
* ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
7. Stem Cell Infusions (before start of protocol treatment):
* ≥ 84 days since allogeneic (non-autologous) bone marrow or stem cell transplant (with or without total body irradiation \[TBI\]) or boost infusion (any stem cell product; not including donor lymphocyte infusion \[DLI\]);
* No evidence of active graft versus host disease (GVHD).
8. Participants who are receiving cyclosporine, tacrolimus or other agents to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial. Participants must be off medications to treat or prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant for at least 14 days prior to enrollment.
9. Cellular Therapy: ≥ 42 days after the completion of donor lymphocyte infusion (DLI) or any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) before start of protocol treatment.
10. Participants with prior exposure to venetoclax are eligible in this trial.
* Adequate organ function:
1. Adequate Renal Function defined as:
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60ml/min/1.73 m\^2, or
* Normal serum creatinine based on age/sex
2. Adequate Liver Function defined as:
* Direct bilirubin \< 1.5 x upper limit of normal (ULN), and
* Alkaline phosphatase ≤ 2.5 x ULN, and
* Serum glutamic pyruvic transaminase (SGPT) alanine aminotransferase (ALT) ≤ 2.5 x ULN. If higher transaminases outside these ranges (up to 5x ULN) are due to a radiographically identifiable leukemia infiltrate, the participant will remain eligible. Transaminase elevation up to 5x ULN is also allowed in case of steatosis on echography.
3. Cardiac performance: Minimum cardiac function defined as:
* No history of congestive heart failure in need of medical treatment
* No pre-treatment diminished left ventricular function on echocardiography (shortening fraction \[SF\] \< 25% or ejection fraction \[EF\] \< 40%)
* No signs of congestive heart failure at presentation of relapse.
* Participant, parent or guardian must sign and date informed consent and pediatric assent (when required), prior to the initiation of screening or study specific procedures, according to local law and legislation.
Exclusion Criteria
* Participants with Down syndrome.
* Participants with Acute promyelocytic leukemia (APL) or Juvenile myelomonocytic leukemia (JMML).
* Participants with isolated CNS3 disease or symptomatic CNS3 disease.
* Participants with malabsorption syndrome or any other condition that precludes enteral administration of venetoclax.
* Participants who are currently receiving an investigational drug other than those specified for this study.
* Participants with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known congenital bone marrow failure syndrome.
* Participants with known prior allergy to any of the medications used in protocol therapy.
* Participants with documented active, uncontrolled infection at the time of study entry.
* Known hepatitis C virus (HCV), hepatitis B virus (HBV) (known positive hepatitis B virus (HBV) surface antigen (HBsAg) results), or human immunodeficiency virus (HIV) infection.
* Concomitant Medications
* Participants who have received strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort within 7 days of the start of study treatment.
* Participants who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit within 3 days of the start of study treatment.
* Participants who have hypersensitivity to the active substance or to any of the excipients listed in summary of product characteristics (SPC).
* Pregnancy or Breast-Feeding:
* Participants who are pregnant or breast-feeding.
* Participants of reproductive potential may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of study therapy and at least 30 days after last dose of venetoclax, or 7 months after gemtuzumab ozogamicin treatment, or for 6 months after the completion of all study therapy, whichever is longer.
* Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of study therapy and at least 30 days after last dose of venetoclax or 4 months after last dose of gemtuzumab ozogamicin, 6 months from the last dose of cytarabine, or 90-days after last exposure to any other chemotherapy, whichever is longer.
Additional criteria to receive a gemtuzumab ozogamicin infusion:
Gemtuzumab ozogamicin should not be given:
* to participants with history of veno-occlusive disease (VOD)/Sinusoidal obstruction syndrome (SOS) grade 3 or 4
* to participants with CD33 negative leukemic blasts (determined at local lab)
Note that these participants are eligible for the study but will not be treated with gemtuzumab ozogamicin.
29 Days
21 Years
ALL
No
Sponsors
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Princess Maxima Center for Pediatric Oncology (European Sponsor)
UNKNOWN
AbbVie
INDUSTRY
Roche-Genentech
INDUSTRY
EuPAL
UNKNOWN
PedAL BCU, LLC
OTHER
Responsible Party
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Principal Investigators
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Seth Karol, MD
Role: PRINCIPAL_INVESTIGATOR
St. Jude Children's Research Hospital
Locations
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Phoenix Children's Hospital
Phoenix, Arizona, United States
Arkansas Children's Hospital
Little Rock, Arkansas, United States
MemorialCare Miller Children's and Women's Hospital Long Beach
Long Beach, California, United States
Children's Hospital of Orange County Main Campus - Orange
Orange, California, United States
Benioff Children's Hospital - Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
Yale University
New Haven, Connecticut, United States
Nemours Alfred I. Dupont Hospital for Children
Wilmington, Delaware, United States
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, United States
University of Florida Health Shands Children's Hospital
Gainesville, Florida, United States
Nemours Children's Specialty Care Jacksonville
Jacksonville, Florida, United States
Nemours Children's Hospital - Orlando
Orlando, Florida, United States
Saint Joseph's Hospital - Tampa
Tampa, Florida, United States
Children's Healthcare of Atlanta
Atlanta, Georgia, United States
Kapi'olani Medical Center for Women and Children
Honolulu, Hawaii, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Comer Children's Hospital
Chicago, Illinois, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
University of Iowa Stead Family Children's Hospital
Iowa City, Iowa, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States
Children's Hospital of Michigan
Detroit, Michigan, United States
Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
The Children's Mercy Hospital - Adele Hall Campus
Kansas City, Missouri, United States
Washington University School of Medicine in St. Louis
St Louis, Missouri, United States
Alliance for Childhood Diseases dba Cure 4 The Kids Foundation
Las Vegas, Nevada, United States
Hackensack University Medical Center, HMH
Hackensack, New Jersey, United States
Morristown Medical Center
Morristown, New Jersey, United States
Columbia University Irving Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center - New York
New York, New York, United States
Cohen Children's Medical Center
Queens, New York, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Doernbecher Children's Hospital
Portland, Oregon, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Prisma Health Richland Hospital
Columbia, South Carolina, United States
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Monroe Carell Jr. Children's Hospital at Vanderbilt
Nashville, Tennessee, United States
Harold C. Simmons Comprehensive Cancer Center
Dallas, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Primary Children's Hospital
Salt Lake City, Utah, United States
Children's Hospital of Richmond at Virginia Commonwealth University
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Children's Health Queensland Hospital and Health Service
South Brisbane, Queensland, Australia
The Royal Children's Hospital - Children's Cancer Centre
Parkville, Victoria, Australia
Perth Children's Hospital
Nedlands, Western Australia, Australia
Sankt Anna-Kinderspital
Vienna, , Austria
Universitair Ziekenhuis Gent
Ghent, Oost-Vlaanderen, Belgium
Alberta Children's Hospital
Calgary, Alberta, Canada
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
CancerCare Manitoba
Winnipeg, Manitoba, Canada
Izaak Walton Killam (IWK) Health Center
Halifax, Nova Scotia, Canada
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada
SickKids - The Hospital for Sick Children
Toronto, Ontario, Canada
Fakultni nemocnice v Motole
Prague, Prague, Czechia
Rigshospitalet
Copenhagen, Capital Region, Denmark
Uusi Lastensairaala
Helsinki, Etelä-Suomen Lääni, Finland
CHU de Toulouse - Hôpital des Enfants
Toulouse, Haute-Garonne, France
Hôpital Jeanne de Flandre
Loos, Hauts-de-France, France
CHU de Nantes - Hôpital Femme-Enfant-Adolescent
Nantes, Loire-Atlantique, France
Institut d'Hématologie et d'Oncologie Pédiatrique
Lyon, Rhône, France
Hôpital Armand-Trousseau
Paris, Île-de-France Region, France
Hôpital Universitaire Robert-Debré
Paris, Île-de-France Region, France
Universitätsklinikum Augsburg
Augsburg, , Germany
Charité - Universitätsmedizin Berlin
Berlin, , Germany
Universitätsklinikum Frankfurt
Frankfurt, , Germany
Padiatrische Hamatologie und Onkologie
Münster, , Germany
Universitätsklinikum Münster
Münster, , Germany
Schneider Children's Medical Center of Israel
Petach Tikvah, Central District, Israel
Istituto Giannina Gaslini
Genova, Genoa, Italy
Fondazione IRCCS San Gerardo dei Tintori
Monza, Monza and Brianza, Italy
Ospedale Pediatrico Bambino Gesù
Roma, Rome, Italy
Ospedale Infantile Regina Margherita
Torino, Turin, Italy
Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital
Nagoya, Aiti, Japan
Hyogo Prefectural Kobe Children's Hospital
Kobe, Hyōgo, Japan
Saitama Prefectural Children's Medical Center
Saitama-Shi, Saitama, Japan
National Center for Child Health and Development
Setagaya-Ku, Tokyo, Japan
Osaka City General Hospital
Osaka, , Japan
Prinses Maxima Centrum Kinderoncologie
Utrecht, , Netherlands
Starship Children's Hospital
Grafton, Auckland, New Zealand
Oslo Universitetssykehus
Oslo, , Norway
Instituto Portugues De Oncologia De Lisboa Francisco Gentil
Lisbon, Lisbon District, Portugal
Hospital Universitari Vall d'Hebrón
Barcelona, , Spain
Hospital Sant Joan de Déu Barcelona
Barcelona, , Spain
Hospital Infantil Universitario Niño Jesús
Madrid, , Spain
Hospital Universitario La Fe
Valencia, , Spain
Karolinska Universitetssjukhuset Solna
Stockholm, Stockholm County, Sweden
Universitaets - Kinderspital Zürich
Zurich, , Switzerland
Countries
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Central Contacts
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References
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Badawi M, Gopalakrishnan S, Engelhardt B, Palenski T, Karol SE, Rubnitz JE, Menon R, Salem AH. Dosing of Venetoclax in Pediatric Patients with Relapsed Acute Myeloid Leukemia: Analysis of Developmental Pharmacokinetics and Exposure-Response Relationships. Clin Ther. 2024 Oct;46(10):759-767. doi: 10.1016/j.clinthera.2024.09.008. Epub 2024 Oct 5.
Other Identifiers
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2021-003212-11
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
2023-510160-12-00
Identifier Type: CTIS
Identifier Source: secondary_id
ITCC-101/APAL2020D
Identifier Type: -
Identifier Source: org_study_id
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