Venetoclax in Children With Relapsed Acute Myeloid Leukemia (AML)

NCT05183035 | Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: ITCC-101/APAL2020D2021-003212-112023-510160-12-00
• Study Type: interventional
• Target: 130
• Locations: 19 countries
• Sites: 88

Brief Summary

A study to evaluate if the randomized addition of venetoclax to a chemotherapy backbone (fludarabine/cytarabine/gemtuzumab ozogamicin \[GO\]) improves survival of children/adolescents/young adults with acute myeloid leukemia (AML) in 1st relapse who are unable to receive additional anthracyclines, or in 2nd relapse.

Conditions

Acute Myeloid Leukemia

Keywords

Venetoclax; Gemtuzumab Ozogamicin; Fludarabine; Cytarabine; Relapsed refractory; Azacitidine

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Up to 5 years

Secondary Outcomes (15)

• Morphology Event Free Survival (EFS)

  Up to 5 years

• Flow-based Event Free Survival (EFS)

  Up to 5 years

• Flow-based Overall Response Rate (ORR)

  Up to Day 84

• Morphological Overall Response Rate (ORR)

  Up to Day 84

• Duration of Response (DOR)

  Up to 5 years

Study Arms (2)

Arm A: Control Arm without Venetoclax

ACTIVE COMPARATOR

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.

Drug: Fludarabine; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Azacitidine

Arm B: Experimental Arm with Venetoclax

EXPERIMENTAL

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.

Drug: Fludarabine; Drug: Cytarabine; Drug: Gemtuzumab Ozogamicin; Drug: Azacitidine; Drug: Venetoclax

Interventions

Azacitidine DRUG

Intravenous (IV) infusion or subcutaneous injection

Arm A: Control Arm without Venetoclax; Arm B: Experimental Arm with Venetoclax

Venetoclax DRUG

Orally via tablet or powder suspension

Arm B: Experimental Arm with Venetoclax

Fludarabine DRUG

Intravenous (IV) infusion

Arm A: Control Arm without Venetoclax; Arm B: Experimental Arm with Venetoclax

Cytarabine DRUG

Intravenous (IV) infusion

Arm A: Control Arm without Venetoclax; Arm B: Experimental Arm with Venetoclax

Gemtuzumab Ozogamicin DRUG

Intravenous (IV) infusion

Arm A: Control Arm without Venetoclax; Arm B: Experimental Arm with Venetoclax

Eligibility Criteria

• Age: 29 Days - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must have enrolled on APAL2020SC, NCT Number: NCT04726241 prior to enrollment on ITCC-101/APAL2020D. (This is only applicable for participants in USA/Canada/Australia/New Zealand sites/Blood Cancer United territory).
• Participants must be ≥ 29 days of age and ≤ 21 years of age at enrollment.
• Participants must have one of the following:
• 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.
• 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:
• 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.
• Intrathecal cytotoxic therapy: No wash-out time is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
• 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.
• 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.
• 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.
• Radiation therapy (RT) (before start of protocol treatment):

You may not qualify if:

• Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study, are not eligible.
• 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:

Sponsors & Collaborators

• PedAL BCU, LLC: lead
• Princess Maxima Center for Pediatric Oncology (European Sponsor): collaborator
• AbbVie: collaborator
• Roche-Genentech: collaborator
• EuPAL: collaborator

Study Sites (89)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

MemorialCare Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

RECRUITING

Children's Hospital of Orange County Main Campus - Orange

Orange, California, 92868, United States

RECRUITING

Benioff Children's Hospital - Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University

New Haven, Connecticut, 06511, United States

RECRUITING

Nemours Alfred I. Dupont Hospital for Children

Wilmington, Delaware, 19803, United States

RECRUITING

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

RECRUITING

University of Florida Health Shands Children's Hospital

Gainesville, Florida, 32610, United States

RECRUITING

Nemours Children's Specialty Care Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

Nemours Children's Hospital - Orlando

Orlando, Florida, 32827, United States

RECRUITING

Saint Joseph's Hospital - Tampa

Tampa, Florida, 33607, United States

RECRUITING

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

RECRUITING

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

RECRUITING

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Comer Children's Hospital

Chicago, Illinois, 60637, United States

RECRUITING

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Stead Family Children's Hospital

Iowa City, Iowa, 52242, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109-4259, United States

RECRUITING

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

RECRUITING

Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

The Children's Mercy Hospital - Adele Hall Campus

Kansas City, Missouri, 64108, United States

RECRUITING

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Alliance for Childhood Diseases dba Cure 4 The Kids Foundation

Las Vegas, Nevada, 89135, United States

RECRUITING

Hackensack University Medical Center, HMH

Hackensack, New Jersey, 07601, United States

RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Memorial Sloan Kettering Cancer Center - New York

New York, New York, 10065, United States

RECRUITING

Cohen Children's Medical Center

Queens, New York, 11040, United States

RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105-3678, United States

RECRUITING

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

RECRUITING

Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

RECRUITING

Children's Hospital of Richmond at Virginia Commonwealth University

Richmond, Virginia, 23219, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Children's Health Queensland Hospital and Health Service

South Brisbane, Queensland, 4101, Australia

RECRUITING

The Royal Children's Hospital - Children's Cancer Centre

Parkville, Victoria, 3052, Australia

RECRUITING

Perth Children's Hospital

Nedlands, Western Australia, 6009, Australia

RECRUITING

Sankt Anna-Kinderspital

Vienna, 1090, Austria

RECRUITING

Universitair Ziekenhuis Gent

Ghent, Oost-Vlaanderen, 9000, Belgium

RECRUITING

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

COMPLETED

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

Izaak Walton Killam (IWK) Health Center

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

RECRUITING

SickKids - The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

RECRUITING

Fakultni nemocnice v Motole

Prague, Prague, 150 06, Czechia

RECRUITING

Rigshospitalet

Copenhagen, Capital Region, 2100, Denmark

RECRUITING

Uusi Lastensairaala

Helsinki, Etelä-Suomen Lääni, FI-00290, Finland

RECRUITING

CHU de Toulouse - Hôpital des Enfants

Toulouse, Haute-Garonne, 31059, France

RECRUITING

Hôpital Jeanne de Flandre

Loos, Hauts-de-France, 59120, France

RECRUITING

CHU de Nantes - Hôpital Femme-Enfant-Adolescent

Nantes, Loire-Atlantique, 44093, France

RECRUITING

Institut d'Hématologie et d'Oncologie Pédiatrique

Lyon, Rhône, 69008, France

RECRUITING

Hôpital Armand-Trousseau

Paris, Île-de-France Region, 75012, France

RECRUITING

Hôpital Universitaire Robert-Debré

Paris, Île-de-France Region, 75019, France

RECRUITING

Universitätsklinikum Augsburg

Augsburg, 86156, Germany

RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Padiatrische Hamatologie und Onkologie

Münster, 48149, Germany

RECRUITING

Universitätsklinikum Münster

Münster, 49149, Germany

RECRUITING

Schneider Children's Medical Center of Israel

Petach Tikvah, Central District, 4920235, Israel

RECRUITING

Istituto Giannina Gaslini

Genova, Genoa, 16147, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, Monza and Brianza, 20900, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, Rome, 00165, Italy

RECRUITING

Ospedale Infantile Regina Margherita

Torino, Turin, 10126, Italy

RECRUITING

Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital

Nagoya, Aiti, 453-8511, Japan

RECRUITING

Hyogo Prefectural Kobe Children's Hospital

Kobe, Hyōgo, 650-0047, Japan

RECRUITING

Saitama Prefectural Children's Medical Center

Saitama-Shi, Saitama, 330-8777, Japan

RECRUITING

National Center for Child Health and Development

Setagaya-Ku, Tokyo, 157-8535, Japan

RECRUITING

Osaka City General Hospital

Osaka, 534-0021, Japan

RECRUITING

Prinses Maxima Centrum Kinderoncologie

Utrecht, 3584 CS, Netherlands

RECRUITING

Starship Children's Hospital

Grafton, Auckland, 1023, New Zealand

RECRUITING

Oslo Universitetssykehus

Oslo, 0372, Norway

RECRUITING

Instituto Portugues De Oncologia De Lisboa Francisco Gentil

Lisbon, Lisbon District, 1099-023, Portugal

RECRUITING

Hospital Universitari Vall d'Hebrón

Barcelona, 08035, Spain

RECRUITING

Hospital Sant Joan de Déu Barcelona

Barcelona, 08950, Spain

RECRUITING

Hospital Infantil Universitario Niño Jesús

Madrid, 28009, Spain

RECRUITING

Hospital Universitario La Fe

Valencia, 46026, Spain

RECRUITING

Karolinska Universitetssjukhuset Solna

Stockholm, Stockholm County, 171 76, Sweden

RECRUITING

Universitaets - Kinderspital Zürich

Zurich, 8032, Switzerland

RECRUITING

Related Publications (1)

• 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.

  PMID: 39368878 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

fludarabine; Cytarabine; Gemtuzumab; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aza Compounds; Organic Chemicals; Ribonucleosides

Study Officials

• Seth Karol, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gwen Nichols, MD

CONTACT

914-821-8217; gwen.nichols@lls.org

Michel Zwaan

CONTACT

+31 88 972 5206; c.m.zwaan@prinsesmaximacentrum.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2021
• First Posted: January 10, 2022
• Study Start: October 1, 2022
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2031
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); FR (6); CH (1); AU (3); FI (1); IL (1); JP (5); DK (1); DE (5); CZ (1); CA (6); NL (1); NZ (1); ES (4); IT (4); US (44); NO (1); PT (1); SE (1)