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Modified Chemotherapy Regimen and Gemtuzumab Ozogamicin for the Treatment of Newly Diagnosed Acute Myeloid Leukemia in Pediatric Patients

Trial Status: Approved

This phase I trial studies how well a modified chemotherapy regimen with gemtuzumab ozogamicin works for the treatment of newly diagnosed acute myeloid leukemia in pediatric patients. The current standard of care to treat most pediatric patients with acute myeloid leukemia is 5 cycles of chemotherapy. Adjusting treatment with a 4-cycle treatment regimen may provide the same treatment results and decrease the amount of side effects experienced during treatment. Gemtuzumab ozogamicin is a monoclonal antibody, gemtuzumab, linked to a toxic agent called calicheamicin. Gemtuzumab attaches to CD33 positive cancer cells in a targeted way and delivers calicheamicin to kill them. Giving gemtuzumab ozogamicin with the 4-cycle treatment regimen may also reduce the chances of acute myeloid leukemia coming back after initial treatment.

Inclusion Criteria

  • 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)
  • 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 * Note: Enrollment may occur pending results of clinically indicated studies to exclude these conditions
  • Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
  • Pregnancy and breast feeding: * Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained * Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs * Lactating females are not eligible unless they have agreed not to breastfeed their infants

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: APPROVED
Contact: Himalee Shreekant Sabnis
Phone: 404-727-3285

PRIMARY OBJECTIVE:

I. To estimate the event-free survival (EFS) for newly diagnosed patients with pediatric acute myeloid leukemia using a risk stratified approach, including a modified chemotherapy regimen alone for subjects with low-risk features and allogeneic bone marrow transplantation for those with high risk features.

SECONDARY OBJECTIVES:

I. To estimate the overall survival (OS) for newly diagnosed patients with pediatric acute myeloid leukemia.

II. To estimate frequency of minimal residual disease (MRD) negative status after one cycle of induction chemotherapy for acute myeloid leukemia (AML) patients who received gemtuzumab ozogamicin (GO) and those that did not receive GO.

III. To estimate the disease-free survival (DFS) for patients who are minimal residual disease (MRD) negative after induction 1, but lack high risk or lowest risk molecular and cytogenetic features as currently classified.

IV. To estimate the incidence of early and late cardiotoxicity in patients with de novo AML that receive the four-cycle Aflac-AML regimen with the inclusion of dexrazoxane.

EXPLORATORY OBJECTIVE:

I. To describe the prevalence of molecular abnormalities in de-novo AML samples using comprehensive genomic testing.

OUTLINE:

INDUCTION I: Patients receive cytarabine intrathecally (IT) at time of diagnostic lumbar puncture or on day 1, cytarabine intravenously (IV) over 15 minutes on days 1-10, daunorubicin hydrochloride IV over 6 hours on days 1, 3, and 5, etoposide phosphate IV over 4 hours on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on days 6-10. Patients with FLT3-ITD also receive sorafenib tosylate orally (PO) daily on days 11-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

INDUCTION II: Patients receive cytarabine IT on day 1, high dose cytarabine IV over 1-3 hours on days 1-4, mitoxantrone IV over 15-30 minutes on days 3-6. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 7-34. Treatment continues for 28 or 34 days in the absence of disease progression or unacceptable toxicity.

INTENSIFICATION I: Patients receive cytarabine IT on day 1, high dose cytarabine IV over 1-3 hours on days 1-4, and etoposide phosphate IV over 60-120 minutes on days 1-5. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 6-33. Treatment continues for 28 or 33 days in the absence of disease progression or unacceptable toxicity.

INTENSIFICATION II: Patients receive high dose cytarabine IV over 1-3 hours on days 1, 2, 8, and 9 and asparaginase Erwinia chrysanthemi intramuscularly (IM) over 1 hour on days 2 and 9. Patients with FLT3-ITD also receive sorafenib tosylate PO daily on days 11-28. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up annually for 10 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Children's Healthcare of Atlanta - Egleston

Principal Investigator
Himalee Shreekant Sabnis

  • Primary ID AflacLL1901
  • Secondary IDs NCI-2019-07692, IRB00111627
  • Clinicaltrials.gov ID NCT04326439