AAML05P1, Killer Immunoglobulin-like Receptor (KIR) Incompatible Unrelated Donor Hematopoietic Cell Transplantation (HCT) for Refractory and Relapsed Acute Myelogenous Leukemia (AML) and Newly Diagnosed AML with Monosomy 7 or -5/5q- in Children
This study is a collaboration among COG, NMDP and Saint Jude Children[Right Quote]s Research Hospital (SJCRH). Clear communication lines have been established between COG and the search-coordinating unit at NMDP in order to facilitate the rapid identification of a suitably HLA-matched unrelated donor and simultaneous patient and donor KIR typing. At the time of enrollment of eligible patients from COG treatment centers, the NMDP will be notified by the treating physician by faxing an NMDP Enrollment form to the NMDP. High-resolution HLA-typing should be obtained on the patient at time of relapse/study entry, if not already available from prior testing, and will be transmitted to the NMDP. An accelerated donor search will be initiated immediately at no additional charge from the NMDP. Blood samples will be obtained from potential donors in order to perform KIR typing at SJCRH by Dr Wing Leung. We anticipate that donor samples for KIR typing will be obtained by NMDP Donor Centers at the time of confirmatory HLA typing and testing of potential donors. Recipients of oUCB transplant will have KIR compatibility determined from the recipient after transplant and engraftment. We also anticipate that the results of KIR typing will be available at about the same time as confirmatory HLA typing has been completed. See Section 13.2 for sample collection and shipping information for KIR studies. The standard NMDP procedure will be modified to integrate KIR typing into the existing donor selection process.
Children ≥ 1 month and < 30 years of age. Patients with a diagnosis of: Patients with primary refractory AML, defined as ≥ 5% bone marrow blasts after two induction cycles of chemotherapy, or patients with AML or myelodysplastic syndrome with -5/5q- or monosomy 7 without inv(16)/t(16;16) or t(8;21) cytogenetics or NPM or CEBPα mutations, or patients with relapsed AML (≥ 5% bone marrow blasts) who meet the customary WHO criteria for AML35 or patients with AML and high FLT3 internal tandem duplication allelic ratio (high FLT3-ITD AR), defined as greater than 0.4, or all cases of therapy-related AML (therapy-related AML is considered high risk), or Patients with AML, without inv(16)/t(16;16) or t(8;21), monosomy 7, -5/5q-, NPM or CEPBα mutations, or high FLT3-ITD AR, but with evidence of residual AML (≥ 0.1%) at the end of Induction I**; or if a minimal residual disease is not performed, then with > 15% bone marrow blasts by morphology after one induction cycle of chemotherapy. ** Any flow-based MRD is eligible for AAML05P1 for patients not on AAML1031, whereas patients on AAML1031 must utilize the central lab as per the AAML1031 protocol guidelines.
Every effort should be made to achieve remission prior to HSCT but remission is not required for participation in this study.
Children who have previously received chemotherapy or radiation therapy or any antileukemic therapy are eligible for this protocol. This study includes patients with primary induction failure or relapse who have already received initial therapy and who may have gone on to have additional therapy prior to receiving protocol stipulated therapy on AAML05P1. No other cancer chemotherapy or immunomodulating agents will be used. Radiotherapy to localized painful lesions is acceptable. Appropriate antibiotics, blood products, antiemetics, fluids, electrolytes and general supportive care are to be used as necessary. Patients of childbearing potential must have a negative pregnancy test and agree to use an effective birth control method. Lactating patients must agree not to nurse a child while on this trial. All patients and/or their parent or legal guardian must sign a written informed consent. All institutional, FDA, and NCI requirements for human studies must be met.