CD34+Selection for Partially Matched Family or Matched Unrelated Adult Donor Transplant

NCT ID: NCT01049854

Last Updated: 2018-08-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2018-08-31

Brief Summary

CD34+ stem cell selection in children, adolescents and young adults receiving partially matched family donor or matched unrelated adult donor allogeneic bone marrow or peripheral blood stem cell transplant will be safe and well tolerated and be associated with a low incidence of serious (Grade III/IV) acute and chronic graft versus host disease (GVHD).

Detailed Description

The selection of CD34+ cells is associated with the simultaneous depletion of T cells that are responsible for severe acute and chronic graft versus host disease (GVHD). Successful engraftment is reported in adult patients with malignant and non-malignant disease who received CD34+ selected stem cells from HLA-matched or mismatched mobilized peripheral blood (PBSC) or bone marrow.

Study Design:

Selected patients defined in the eligibility criteria will enrolled on this study. Patients will receive one of either full intensity or reduced intensity regimen based on the patient's disease status, organ function and performance and determined by the PI and will have peripheral blood undergo CD34 selection.

Conditions

Leukemia; Lymphoma; Bone Marrow Failure; Immunodeficiencies; Histiocytosis; Sickle Cell Disease; Beta Thalassemia; Inborn Errors of Metabolism

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Thiotepa/Cyclophosphamide/ATG

Full intensity with TBI

Group Type: EXPERIMENTAL

Full Intensity with TBI

Intervention Type: DRUG

Patients will start their pre-conditioning regimen on Day -8. Fractionated TBI will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5, -4, Cyclophosphamide on Days -3, -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Busulfan/Melphalan/ATG

Full intensity without TBI

Group Type: EXPERIMENTAL

Full Intensity

Intervention Type: DRUG

Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with stem cell infusion on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Busulfan/Fludarabine/Alemtuzumab

Reduced Intensity Chemotherapy

Group Type: EXPERIMENTAL

Reduced Intensity

Intervention Type: DRUG

Patients will start their GVHD prophylaxis with Tacrolimus on Day -9. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Fludarabine/Cyclophosphamide/ATG

Reduced Intensity Chemotherapy for Fanconi Anemia

Group Type: EXPERIMENTAL

Reduced Intensity (Fanconi)

Intervention Type: DRUG

Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and antithymocyte globulin (horse) on Days -5, -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Interventions

Full Intensity with TBI

Patients will start their pre-conditioning regimen on Day -8. Fractionated TBI will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5, -4, Cyclophosphamide on Days -3, -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Intervention Type: DRUG

Full Intensity

Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with stem cell infusion on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Intervention Type: DRUG

Reduced Intensity

Patients will start their GVHD prophylaxis with Tacrolimus on Day -9. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Intervention Type: DRUG

Reduced Intensity (Fanconi)

Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and antithymocyte globulin (horse) on Days -5, -4, -3, -2 and -1. The stem cell infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus only.

Intervention Type: DRUG

Other Intervention Names

ThioTepa; Cytoxan; Atgam; Myleran; Alkeran; Atgam; Fludara; Myleran; Campath; Fludara; Cytoxan; Atgam

Eligibility Criteria

Inclusion Criteria

• Adequate renal function defined as:Serum creatinine <1.5 x normal, or Creatinine clearance or radioisotope GFR >60 ml/min/m2 or an equivalent GFR as determined by the institutional normal range.
• Adequate liver function defined as:Total bilirubin <1.5 x normal, or SGOT (AST) or SGPT (ALT) <3.0 x normal
• Adequate cardiac function defined as:Shortening fraction >27% by echocardiogram, or Ejection fraction of >47% by radionucleotide angiogram or echocardiogram.
• Adequate pulmonary function defined as:Uncorrected DLCO >50% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% on room air.

Eligibility for Reduced Intensity Regimen:

• Adequate renal function defined as:Serum creatinine 2.0 x normal, or creatinine clearance or radioisotope GFR > 40 ml/min/m2 or an equivalent GFR as determined by the institutional normal range.
• Adequate liver function defined as:Total bilirubin < 2.5 x normal; or SGOT (AST) or SGPT (ALT) < 5.0 x normal.
• Adequate cardiac function defined as:Shortening fraction of >25% by echocardiogram, or Ejection fraction of >40% by radionuclide angiogram or echocardiogram.
• Adequate pulmonary function defined as:DLCO >35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry >94% in room air.

Exclusion Criteria

• Pregnancy/Breast Feeding: Females who are pregnant or breast-feeding are not eligible.
• Infection: Patients with documented uncontrolled infection at the time of study entry are not eligible.

• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell S Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical College

Locations

New York Medical College

Valhalla, New York, United States

Countries

United States

Other Identifiers

NYMC 525

Identifier Type: OTHER

Identifier Source: secondary_id

L 10,321

Identifier Type: -

Identifier Source: org_study_id