Trials / Completed

CompletedNCT00448201

Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Allogeneic Hematopoietic Cell Transplantation for Patients With Hematologic Disorders Who Are Ineligible or Inappropriate for Treatment With a More Intensive Therapeutic Regimen

Status: Completed
Phase: Phase 2
Study type: Interventional
Enrollment: 71 (actual)

Sponsor: UNC Lineberger Comprehensive Cancer Center · Academic / Other
Sex: All
Age: 10 Years
Healthy volunteers: Not accepted

Summary

RATIONALE: Giving low doses of chemotherapy, such as busulfan and fludarabine, before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. It also helps stop 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 or abnormal cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Immunosuppressive therapy may improve bone marrow function and may be an effective treatment for hematologic cancer or other disease. PURPOSE: This clinical trial is studying the side effects and how well giving busulfan and fludarabine with or without antithymocyte globulin followed by donor stem cell transplant works in treating patients with hematologic cancer or other disease.

Detailed description

OBJECTIVES: Primary * Determine the clinical efficacy and toxicity profiles of a nonmyeloablative preparative regimen comprising busulfan and fludarabine with or without anti-thymocyte globulin followed by allogeneic hematopoietic stem cell transplantation in patients with hematologic cancers or other diseases. * Determine the feasibility of this regimen in these patients. * Establish a treatment-related mortality during the first 6 months that is less than 20% in patients treated with this regimen. Secondary * Determine the response rates (disease-specific partial response and complete response) in patients treated with this regimen. * Determine overall and progression-free survival of patients treated with this regimen. * Determine the percent donor chimerism and immunologic recovery, including dendritic cell recovery, in patients treated with this regimen. * Determine the risk of acute and chronic graft-versus-host disease and other toxicities in patients treated with this regimen. * Assess the overall nonhematologic grades 3 and 4 toxicity of this regimen, including the incidence of veno-occlusive disease and pulmonary toxicity, in these patients. OUTLINE: Patients are assigned to 1 of 4 treatment groups according to disease type and donor type. * Preparative regimen: * Group 1 (patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), IPSS (International Prognostic Scoring System score) high-risk myelodysplastic syndromes (HR MDS), or chronic myelogenous leukemia (CML) with an human leukocyte antigen (HLA)-matched related donor (MRD): Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV continuously over 48 hours on days -6 and -5. * Group 2 (patients with AML, ALL, IPSS HR MDS, or CML with an HLA-matched unrelated donor (MUD) or mismatched related donor (MMRD)): Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on day -8. * Group 3 (patients with all other diseases with a MRD): Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin as in group 2. * Group 4 (patients with all other disease with a MUD or MMRD): Patients receive fludarabine phosphate and busulfan as in group 1 and anti-thymocyte globulin IV over 4 hours on days -8 and -7. * Allogeneic stem cell transplantation: All patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously once daily beginning on day 5 (groups 1 and 2) or day 7 (groups 3 and 4) and continuing until blood counts recover. * Graft-vs-host disease (GVHD) prophylaxis: All patients receive oral tacrolimus twice daily on days -1 to 120 followed by a taper until day 180. Patients in groups 1 and 2 also receive methotrexate IV on days 1, 3, and 6. * Donor lymphocyte infusion (DLI): After day 120, patients with progressive disease or stable disease while off immunosuppression and with no evidence of active GVHD may receive DLI. Treatment with DLI may repeat every 8 weeks for up to 3 total infusions in the absence of disease response or GVHD. Peripheral blood and/or bone marrow samples are collected at baseline and then at 30, 60, 90, 120, and 180 days post-transplantation. Chimerism (including the following subsets: whole blood, T-cells as defined by cluster of differentiation 3 (CD3) positivity, B-cells as defined by Cluster of Differentiation 19 (CD19) positivity, and myeloid cells as defined by Cluster of Differentiation 14 (CD14) and Cluster of Differentiation 15 (CD15) positivity is analyzed by polymerase chain reaction technology. After restaging between Days 90 and 100 and between Days 150 to 180, patients are followed every 6 months for 1 years and then yearly for a maximum of 5 years from study entry.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	anti-thymocyte globulin	0.5 mg/kg on day -3, 2.5 mg/kg on day -2 (groups 2, 3 and 4) and 3 mg/kg on day -1 (group 4 only)
BIOLOGICAL	sargramostim	GM-CSF 500 ug everyday (QD) subcutaneously will be given to recipients who remain with an Absolute neutrophil count (ANC) \< 1000/microliter (uL) past day 20
BIOLOGICAL	therapeutic allogeneic lymphocytes	A minimum total cluster of differentiation 34 (CD34)+ cell dose of 3 x 10\^6 cells/kg and a maximum 8 x 10\^6 cells/kg will be infused on day 0
DRUG	busulfan	6.4 mg/kg by continuous IV infusion over 48 hours on Days -6 and -5
DRUG	fludarabine phosphate	fludarabine 30 mg/m\^2/day x 5 days IV piggyback (IVPB) over 30 minutes on Days -7 through -3
DRUG	methotrexate	Methotrexate 5 mg/m\^2 per day on days +1, +3 and +6
DRUG	tacrolimus	Suggested starting dose is 0.03 mg/kg po bid starting on Day -1
PROCEDURE	nonmyeloablative allogeneic hematopoietic stem cell transplantation	Minimum total CD34+ cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on Day 0
PROCEDURE	peripheral blood stem cell transplantation	Minimum total CD34+ cells of 3 x 10\^6 cells/kg and a maximum of 8 x 10\^6 cells/kg will be infused on Day 0

Timeline

Start date: 2011-01-07
Primary completion: 2011-01-11
Completion: 2012-05-23
First posted: 2007-03-16
Last updated: 2017-05-30
Results posted: 2017-05-30

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00448201. Inclusion in this directory is not an endorsement.