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

Lymphoma Clinical Trial

Official title:

CD34+Stem Cell Selection for Patients Receiving Partially Matched Family or Matched Unrelated Adult Donor Allogeneic Stem Cell Transplantations for Malignant and Non-Malignant Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01049854
• Other study ID #: L 10,321
• Secondary ID: NYMC 525
• Status: Completed
• Phase: Phase 2
• Start date: September 2011
• Est. completion date: August 2018

Study information

• Verified date: August 2018
• Source: New York Medical College
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 2018
• Est. primary completion date: November 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Beta Thalassemia
• beta-Thalassemia
• Bone Marrow Failure
• Histiocytosis
• Immunodeficiencies
• Immunologic Deficiency Syndromes
• Inborn Errors of Metabolism
• Leukemia
• Lymphoma
• Metabolism, Inborn Errors
• Pancytopenia
• Sickle Cell Disease
• Thalassemia

Intervention

Drug:
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York Medical College

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The safety CD34+ stem cell selection	serious adverse events will be monitored post transplant to determine if there is an increase vs. historical data related to the CD34+ selection	100 days
Secondary	Immune reconstitution (T, B, DC) following CD34+ selection	immune subsets will be drawn post transplant to determine the rate of reconstitution post CD34+ transplant to determine if this process increases or decreases the reconstitution time.	3 years