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
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|ClinicalTrials.gov Identifier: NCT00553202|
Recruitment Status : Active, not recruiting
First Posted : November 5, 2007
Results First Posted : February 24, 2017
Last Update Posted : February 24, 2017
RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may stop this from happening.
PURPOSE: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting leukemia. Bone marrow donors can be selected based on the type of NK cells they have, specifically the killer immunoglobulin receptor (KIR) type. This study provides information on KIR type from potential donors, which can be used in selecting the bone marrow donor. This phase II trial of unrelated donor stem cell transplant in patients with high risk AML (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of the patients and potential donors will be available to the treating transplant physician at the time of donor selection.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia||Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Drug: methylprednisolone Drug: tacrolimus Other: laboratory biomarker analysis Other: pharmacological study Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation||Phase 2|
- 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.
OUTLINE: This is a multicenter study.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||158 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||June 2016|
Experimental: Treatment (chemotherapy and allogeneic 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.
Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0.
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 pharmacological study objectives
Biological: anti-thymocyte globulin
Given IV or orally
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: allogeneic bone marrow transplantation
allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic hematopoietic SCT
- Overall Survival (OS) [ Time Frame: At 5 years from HSCT date ]OS - Time from HSCT until death
- Cumulative Incidence of NK Cell Reconstitution [ Time Frame: At 5 years from HSCT date ]Cumulative incidence of successful reconstitution to donor level is calculated.
- Disease-free Survival [ Time Frame: From the date of SCT to the date of relapse, the date of death, or the date of last follow-up, whichever occurs first ]The cumulative incidence of relapse or death after SCT will be calculated by considering relapse and death due to other causes as competing events.
- Acute and Chronic Graft-versus-host Disease [ Time Frame: Up to 5 years ]Acute and chronic GVHD will be summarized.
- Time to the Donor-specific NK-cell Receptor Expression [ Time Frame: Up to 42 days after SCT ]The presence of donor cells is demonstrated by the detection of informative variable-number tandem-repeat polymorphisms or by fluorescent in situ hybridization with a Y-chromosome-specific probe in cases of sex-mismatched transplants. Independent variables that will be examined include donor-recipient KIR mismatch, taking into consideration the interactions with donor-recipient human leukocyte antigen (HLA) compatibility, and the numbers of CD34+ cells and CD3+ cells in the graft.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00553202
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|Study Chair:||Stella M. Davies, MBBS, PhD||Children's Hospital Medical Center, Cincinnati|