Donor Stem Cell Transplant in Treating Young Patients With Acute Myeloid Leukemia With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory or Relapsed Acute Myelogenous Leukemia

Titre officiel

Killer Immunoglobulin-like Receptor (KIR) Incompatible Unrelated Donor Hematopoietic Cell Transplantation (SCT) for AML With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory and Relapsed Acute Myelogenous Leukemia (AML) in Children: A Children's Oncology Group (COG) Study

Sommaire:

L’administration d’une chimiothérapie avant une allogreffe de cellules souches fortement compatibles avec celles du patient aide à inhiber la multiplication des cellules cancéreuses. Ce type de traitement empêche également le rejet des cellules souches du donneur par le système immunitaire du patient. Les cellules souches greffées pourraient remplacer les cellules immunitaires du patient et aider à détruire toute cellule cancéreuse restante (réaction du greffon contre la tumeur). Il arrive parfois que les cellules greffées provenant d’un donneur aient une réponse immunitaire contre les cellules normales du patient greffé. L’administration de globuline antithymocyte avant la greffe ainsi que de cyclosporine, de tacrolimus et de méthotrexate avant et après la greffe pourrait empêcher que cela se produise.

Cet essai de phase II vise à évaluer l’efficacité de l’allogreffe de cellules souches dans le traitement des jeunes patients atteints d’une leucémie aiguë myéloïde récidivante, réfractaire ou nouvellement diagnostiquée.

Description de l'essai

Primary Outcome:

• Overall survival
• Disease-free survival
• Acute and chronic graft-versus-host disease
• Time to NK cell reconstitution
• Time to the donor-specific NK-cell receptor expression

• To define the relationship between the status of donor NK-cell receptor and patient outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD) and umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) in young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3 internal tandem duplication allelic ratio (High-FLT3-ITD AR), or refractory or relapsed acute myelogenous leukemia.

• To correlate the relationships between factors affecting NK receptor status and clinical events.

• To assess NK-cell development after URD and UCB HCT in patients with poor prognosis AML.

• To evaluate NK-cell reconstitution and receptor-acquisition pattern in these patients.

• Preparative regimen: Patients receive 1 of the following regimens:

• Hematopoietic stem cell transplantation (SCT): Patients receive busulfan IV every 6 hours on days -9 to -6, high-dose cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV once or twice daily over 4 hours on days -3 to -1, and methylprednisolone IV on days -3 to -1.

• Umbilical cord blood (UCB) transplantation: Conditioning regimen, infusion procedures, and post-transplant immunoprophylaxis for patients with an UCB donor are according to institutional guidelines and standards.

• Allogeneic hematopoietic stem cell transplantation (SCT) or umbilical cord blood (UCB) transplant: Patients undergo allogeneic SCT or UCB transplant on day 0.

• Graft-vs-host disease (GVHD) prophylaxis: Patients receive cyclosporine or tacrolimus IV or orally beginning on day -2 and continuing until day 50, followed by a taper until week 24. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Blood samples will be collected periodically from both patients and donors for studies of natural killer cells in support of the study objectives. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.

Voir cet essai sur ClinicalTrials.gov