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

NCT01049854 | Completed Phase 2

• 2 other identifiers: L 10,321NYMC 525
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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).

Conditions

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

Keywords

unrelated donor transplant; CD34 selection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Immune reconstitution (T, B, DC) following CD34+ selection

  3 years

Study Arms (4)

Thiotepa/Cyclophosphamide/ATG

EXPERIMENTAL

Full intensity with TBI

Drug: Full Intensity with TBI

Busulfan/Melphalan/ATG

EXPERIMENTAL

Full intensity without TBI

Drug: Full Intensity

Busulfan/Fludarabine/Alemtuzumab

EXPERIMENTAL

Reduced Intensity Chemotherapy

Drug: Reduced Intensity

Fludarabine/Cyclophosphamide/ATG

EXPERIMENTAL

Reduced Intensity Chemotherapy for Fanconi Anemia

Drug: Reduced Intensity (Fanconi)

Interventions

Full Intensity with TBI 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.

Also known as: ThioTepa, Cytoxan, Atgam

Thiotepa/Cyclophosphamide/ATG

Full Intensity 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.

Also known as: Myleran, Alkeran, Atgam

Busulfan/Melphalan/ATG

Reduced Intensity 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.

Also known as: Fludara, Myleran, Campath

Busulfan/Fludarabine/Alemtuzumab

Reduced Intensity (Fanconi) 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.

Also known as: Fludara, Cytoxan, Atgam

Fludarabine/Cyclophosphamide/ATG

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York Medical College: lead

Study Sites (1)

New York Medical College

Valhalla, New York, 10595, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Bone Marrow Failure Disorders; Immunologic Deficiency Syndromes; Histiocytosis; Anemia, Sickle Cell; beta-Thalassemia; Metabolism, Inborn Errors

Interventions

Whole-Body Irradiation; Thiotepa; Cyclophosphamide; Antilymphocyte Serum; Busulfan; Melphalan; fludarabine phosphate; Alemtuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramides; Organophosphorus Compounds; Organic Chemicals; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal

Study Officials

• Mitchell S Cairo, MD

  New York Medical College

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: January 15, 2010
• Study Start: September 1, 2011
• Primary Completion: November 1, 2017
• Study Completion: August 1, 2018
• Last Updated: August 21, 2018

Record last verified: 2018-08

Locations

US (1)