AflacLL1901 (CHOA-AML)

NCT04326439 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00111627
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to study an Aflac-AML chemotherapy backbone prospectively to validate its use in all pediatric AML and to further evaluate the cardiotoxicity with this approach for low risk AML.

Conditions

Acute Myeloid Leukemia; AML, Childhood

Keywords

acute myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Event-free Survival (EFS) in Low Risk Patients and High Risk Patients

  Event-free survival defined as the time from on study to death, failure to achieve remission or relapse in newly diagnosed patients with pediatric acute myeloid leukemia in the Low risk stratification group and High risk stratification group

  Up to 2 years post-intervention

Secondary Outcomes (6)

• Overall Survival (OS)

  Up to 2 years post-intervention

• Minimal Residual Disease (MRD) Negative Status

  Post-induction I, an average of 28 days

• Disease-free Survival (DFS) for Patients Who Are MRD Negative

  Up to 2 years post-intervention

• Cardiotoxicity in Patients With de Novo AML That Receive the Four-cycle Aflac-AML Regimen With the Inclusion of Dexrazoxane

  At completion of Cycle 4 (each cycle average is 28 days)

• Proportion of Patients Who Develop Infection and/or Febrile Neutropenia During Each Treatment Course

  At the end of each cycle (each cycle average is 28 days)

Study Arms (2)

Aflac-AML Regimen for Low Risk AML Patients

EXPERIMENTAL

Participants in this arm will receive the standard Aflac-AML Regimen with the following chemotherapy: * Induction-1: patients on Induction-I will receive gemtuzumab + ADE therapy based on genotyping. Lasts a total of 28 days. * Induction II - MA * Intensification I - AE * Intensification II - HD ARAC/LASP Patients with low risk status who had low risk markers and were MRD positive at the end of Induction I and continue to be MRD positive after Induction II will come off protocol.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Erwinase; Drug: Etoposide; Drug: Gemtuzumab ozogamicin

Aflac-AML Regimen for High Risk AML Patients

EXPERIMENTAL

Participants in this arm will receive standard Aflac-AML Regimen with the following chemotherapy: * Induction-1: patients will receive gemtuzumab in addition to ADE therapy based on genotyping. Induction I lasts a total of 28 days. * Induction 1 for FLT3-ITD patients - ADE (10+3+5) with GO with Sorafenib * Induction II - MA * Induction II for FLT3-ITD patients - MA with Sorafenib * Intensification I - AE * Intensification I for FLT3-ITD patients - AE with sorafenib * Intensification II - HD ARAC/LASP * Intensification II for FLT3-ITD patients - HD ARAC/LASP with sorafenib * Hematopoietic stem cell transplantation (HSCT) If a patient is classified as High risk after Induction I, they may proceed to best allogenic donor SCT following Induction II. These patients may receive a third course of chemotherapy prior to HSCT. In cases where HSCT is not an option, patients can receive 4 cycles of chemotherapy. Only patients with FLT3-ITD mutation will receive sorafenib.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Erwinase; Drug: Etoposide; Drug: Gemtuzumab ozogamicin; Procedure: Stem cell transplantation (SCT); Drug: Sorafenib

Interventions

Cytarabine DRUG

100 mg/m²/dose every 12 hours IV Days 1-10

Also known as: cytosine arabinoside, ARA-C

Aflac-AML Regimen for High Risk AML Patients; Aflac-AML Regimen for Low Risk AML Patients

Daunorubicin DRUG

50 mg/m²/dose IV Days 1, 3, 5

Also known as: Rubidomycin

Aflac-AML Regimen for High Risk AML Patients; Aflac-AML Regimen for Low Risk AML Patients

Erwinase DRUG

25,000 International Units/m²/dose IM Days 2, 9

Also known as: Erwinaze, Erwinia L-Asparaginase, Erwinia Chrysanthemi L-asparaginase, Crisantaspase

Aflac-AML Regimen for High Risk AML Patients; Aflac-AML Regimen for Low Risk AML Patients

Etoposide DRUG

150 mg/m²/dose IV Days 1-5

Also known as: VePesid, VP-16

Aflac-AML Regimen for High Risk AML Patients; Aflac-AML Regimen for Low Risk AML Patients

Gemtuzumab ozogamicin DRUG

Administered as a single 3 mg/m2 dose of GO to be given between days 6-10 during Induction I for patients with CC genotype, in addition to ADE therapy.

Also known as: Mylotarg®, CDP-771, CMA-676, hP67.6-calicheamicin

Aflac-AML Regimen for High Risk AML Patients; Aflac-AML Regimen for Low Risk AML Patients

Stem cell transplantation (SCT) PROCEDURE

Transplantation of multipotent hematopoietic stem cells from bone marrow

Also known as: Hematopoietic stem cell transplantation (HSCT), Bone Marrow Transplant (BMT)

Aflac-AML Regimen for High Risk AML Patients

Sorafenib DRUG

200 mg/m2/dose daily, rounded to accommodate tablet size. The maximum dose will be 400 mg. Days 7 through 34.

Also known as: BAY 43-9006 Tosylate, BAY 54-9085 Nexavar

Aflac-AML Regimen for High Risk AML Patients

Eligibility Criteria

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

You may qualify if:

• Age: Patients must be less than 21 years of age at the time of study enrollment
• Diagnosis: Patients must be newly diagnosed with AML
• Patients with previously untreated primary AML who meet the customary criteria for AML with ≥ 20% bone marrow blasts as set out in the 2016 WHO Myeloid Neoplasm Classification are eligible.
• Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive. In cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/FISH testing is feasible can be substituted for the marrow exam at diagnosis.
• Patients with \<20% bone marrow blasts are eligible if they have:
• A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities,
• the unequivocal presence of megakaryoblasts, or
• Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
• Performance Level: Patients with acceptable organ function and any performance status are eligible for enrollment

You may not qualify if:

• Patients with any of the following constitutional conditions are not eligible:
• Fanconi anemia
• Shwachman syndrome
• Any other known bone marrow failure syndrome
• Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: Enrollment may occur, pending results of clinically indicated studies to exclude these conditions.
• Other Excluded Conditions:
• Any concurrent malignancy
• Juvenile myelomonocytic leukemia (JMML)
• Philadelphia chromosome positive AML
• Biphenotypic or bilineal acute leukemia
• Acute promyelocytic leukemia (APL)
• Acute myeloid leukemia arising from myelodysplasia
• Therapy-related myeloid neoplasms

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Egleston Hospital

Atlanta, Georgia, 30322, United States

Location

Related Publications (1)

• Sabnis HS, Minson KA, Monroe C, Allen K, Metts JL, Cooper TM, Woods WG, Castellino SM, Keller FG. A strategy to reduce cumulative anthracycline exposure in low-risk pediatric acute myeloid leukemia while maintaining favorable outcomes. Leuk Res. 2020 Sep;96:106421. doi: 10.1016/j.leukres.2020.106421. Epub 2020 Jul 12.

  PMID: 32683126 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; Daunorubicin; Asparaginase; asparaginase erwinia chrysanthemi recombinant; Etoposide; Gemtuzumab; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Bone Marrow Transplantation; Sorafenib

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; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Calicheamicins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Tissue Transplantation; Phenylurea Compounds; Urea; Amides; Benzene Derivatives; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Results Point of Contact

• Title: Dr. Himalee Sabnis
• Organization: Emory University

hsabnis@emory.edu

404-727-3285

Study Officials

• Himalee Sabnis, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: March 13, 2020
• First Posted: March 30, 2020
• Study Start: January 24, 2020
• Primary Completion: March 15, 2022
• Study Completion: March 15, 2022
• Last Updated: June 15, 2022
• Results First Posted: June 15, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)