NCT00322101

Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

A Multi-center Phase III Study Comparing Myeloablative to Nonmyeloablative Transplant Conditioning in Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Giving chemotherapy, such as fludarabine phosphate, busulfan, and cyclophosphamide, and total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether low-dose chemotherapy and total-body radiation therapy is more effective than high-dose chemotherapy in treating patients with myelodysplastic syndrome or acute myeloid leukemia. PURPOSE: This phase III trial is studying low-dose conditioning to see how well it works compared to high-dose conditioning followed by peripheral blood stem cell transplant in treating patients with myelodysplastic syndromes or acute myeloid leukemia

Detailed description

OBJECTIVES: I. Determine whether the conditioning intensity affects outcomes after HCT in patients with MDS or AML who have \< 5% marrow myeloblasts at the time of HCT. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm I (Nonmyeloablative regimen): CONDITIONING: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive cyclosporine every 12 hours on days -3 to 57 with taper on days 57-177 or cyclosporine every 12 hours on days -3 to 100 with taper on days 101-177. Patients also receive oral mycophenolate mofetil every 12 hours on days 0-27 or every 8 hours on days 0-40 with taper on days 41-96. Arm II (Myeloablative regimen): CONDITIONING: Patients are assigned to 1 of 2 treatment groups. Group A: Patients receive fludarabine IV once daily and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2. Group B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4. TRANSPLANTATION: Patients undergo PBSC infusion on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally every 12 hours on days -1 to 56 and taper on days 57-200. Patients also receive methotrexate IV on days 1, 3, 6, and 11. Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
• Acute Myeloid Leukemia/Transient Myeloproliferative Disorder
• Adult Acute Myeloid Leukemia in Remission
• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Childhood Acute Myeloid Leukemia in Remission
• Childhood Myelodysplastic Syndromes
• de Novo Myelodysplastic Syndromes
• Myelodysplastic Syndrome With Isolated Del(5q)
• Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable
• Previously Treated Myelodysplastic Syndromes
• Recurrent Adult Acute Myeloid Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia
• Secondary Myelodysplastic Syndromes

Interventions

Type	Name	Description
RADIATION	total-body irradiation	Radiation
PROCEDURE	allogeneic hematopoietic stem cell transplantation	Undergo allogeneic transplantation
DRUG	cyclophosphamide	Given IV
DRUG	mycophenolate mofetil	Given orally
DRUG	busulfan	Given IV or orally
DRUG	cyclosporine	Given IV or orally
DRUG	fludarabine phosphate	Given IV
PROCEDURE	peripheral blood stem cell transplantation	Undergo transplantation
PROCEDURE	nonmyeloablative allogeneic hematopoietic stem cell transplantation	Undergo allogeneic transplantation
OTHER	laboratory biomarker analysis	Correlative studies
GENETIC	cytogenetic analysis	Correlative studies
OTHER	flow cytometry	Correlative studies
GENETIC	fluorescence in situ hybridization	Correlative studies
OTHER	pharmacological study	Correlative studies
GENETIC	polymorphism analysis	Correlative studies
DRUG	tacrolimus	Given IV or orally
DRUG	methotrexate	Given IV

Timeline

• Start date: 2006-01-01
• Primary completion: 2012-04-01
• Completion: 2014-10-01
• First posted: 2006-05-04
• Last updated: 2014-10-31
• Results posted: 2013-10-28

Locations

8 sites across 2 countries: United States, Germany