Clinical trial NCT04326439: AflacLL1901 (CHOA-AML)
Official title: CHOA-AML: A Pilot Study for Newly Diagnosed Pediatric Patients With Acute Myeloid Leukemia (AML)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
AML, Childhood
Keywords: acute myeloid leukemia
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2020-03-30
Enrollment: 8
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) to approximately 50% and 65% respectively, with current treatment strategies. Patients with good response to induction and/or those who lack high-risk cytogenetic and molecular features \[classified as low-risk AML (LR-AML)\] have even better outcomes with EFS and OS approaching 70% and 85% respectively; however, treatment-related toxicities remain a major concern. Anthracycline-based therapeutic regimens expose patients to the risk of anthracycline-induced cardiotoxicity. Therefore, strategies that reduce cardiac toxicities using tailored approaches while maintaining and/or improving outcomes are needed for all patients with AML. The Children's Oncology Group (COG) regimens AAML1031 and AAML0531 utilized an anthracycline-intensive backbone for LR-AML with cumulative anthracycline doxorubicin-equivalent doses of up to 492mg/m2. However, high-risk patients treated with chemotherapy alone received an intensified induction chemotherapy (using mitoxantrone-cytarabine) but with overall reduced doses of anthracycline-equivalent (342mg/m2). The investigators piloted an institutional practice to treat all LR-AML patients with four cycle regimen (Aflac-AML) with the goal of reducing cumulative anthracycline exposure, thereby reducing the risk of cardiotoxicity, while providing three high-dose cytarabine courses. In this pilot institutional experience with this approach, they were able to maintain excellent outcomes for this low-risk group with 3-year event-free survival (EFS) and OS of 70.0% ± 0.1% and 85.5% ± 0.08% respectively, from end of course 1. Recent evolution in cytogenetic classification has further delineated risk groups in AML. Gemtuzumab ozogamicin (GO), an antibody-drug conjugate was shown to reduce relapse risk in patients with CC genotype with de-novo AML on COG study AAML0531. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Event-free Survival (EFS) in Low Risk Patients and High Risk Patients
timeFrame: Up to 2 years post-intervention
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 2 years post-intervention
measure: Minimal Residual Disease (MRD) Negative Status
timeFrame: Post-induction I, an average of 28 days
measure: Disease-free Survival (DFS) for Patients Who Are MRD Negative
timeFrame: Up to 2 years post-intervention
measure: Cardiotoxicity in Patients With de Novo AML That Receive the Four-cycle Aflac-AML Regimen With the Inclusion of Dexrazoxane
timeFrame: At completion of Cycle 4 (each cycle average is 28 days)
measure: Proportion of Patients Who Develop Infection and/or Febrile Neutropenia During Each Treatment Course
timeFrame: At the end of each cycle (each cycle average is 28 days)
measure: Duration of Hospital Admission in Patients That Developed Infection and Febrile Neutropenia at the End of Each Treatment Cycle
timeFrame: At the end of each cycle (each cycle average is 28 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Egleston Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Himalee Sabnis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.