Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases

NCT01019876 | Completed Phase 2 DMC

• 2 other identifiers: AAAB0170CHNY-01-509
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This study proposes the use of a reduced intensity chemotherapy/radiation therapy regimen followed by stem cell transplantation, as compared to standard ablative chemotherapy regimens associated with stem cell transplantation, in a population of patients with non-malignant diseases (non-cancer). Eligible patients will have a non-malignant disease in one of the following four strata: bone marrow failure syndromes, immunodeficiencies, inborn errors of metabolism, or histiocytoses. Patients will be assigned to therapy according to diagnosis. Patients will be stratified by disease into one of four strata and treatment regimens will be based on specific disease criteria and conditions. Although these diseases are non-malignant in name, they are often malignant by nature of the disease progression, treatment and associated complications.

Conditions

Bone Marrow Failure; Osteopetrosis; Fanconi Anemia; Severe Combined Immunodeficiency

Keywords

Bone marrow Failure; Fanconi Anemia; Severe Combined Immunodeficiency; Osteopetrosis; Allogeneic Stem Cell Transplantation; Chemotherapy; Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• Number of participants with Adverse Events

  The number of participants with adverse events as assessed by National Cancer Institute (NCI) Common Terminology Criteria Adverse Events (CTCAE - Version 4.0)

  Up to 2 years

Secondary Outcomes (4)

• Risk of disease progression

  Up to 1 year

• Immune reconstitution

  Up to 1 year

• Incidence of graft versus host disease (GVHD)

  Up to 1 year

• Metabolic/Immune reconstitution

  Up to 1 year

Study Arms (4)

Regimen A - Standard Conditioning Regimen

ACTIVE COMPARATOR

Standard conditioning regimen for all diseases except those diseases or conditions noted in Regimen B, C and D: * Fludarabine (180 mg/m2 total dose) * Busulfan (16 mg/kg less than or equal to 4 yrs and 12.8 mg/ kg \>4 yrs total dose) * Alemtuzumab (2mg/m2 x 1day, 6mg/m2 x 2 days, 20mg/m2 x 2days)

Drug: Fludarabine; Drug: Busulfan; Drug: Alemtuzumab

Regimen B

EXPERIMENTAL

Includes patients with a diagnosis of: Osteopetrosis and Severe Aplastic Anemia with a history of \>10 blood transfusions, or Blackfan-Diamond's anemia, or Chronic Granulomatous Disease, or Wiskott Aldrich Syndrome: * Cyclophosphamide (200 mg/kg total dose) * Fludabarine (180 mg/m2 total dose) * Rabbit Anti-thymocyte Globulin (8mg/kg total dose)

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rabbit Anti-thymocyte Globulin

Regimen C

EXPERIMENTAL

Includes patients with any one of the following specific diagnosis: Fanconi Anemia, Dyskeratosis Congenita or Schwachman Diamond Syndrome * Cyclophosphamide (40 mg/kg total dose) * Fludarabine (140 mg/m2 total dose) * Anti-Thymocyte Globulin (horse) (150mg/kg total dose)/TBI 450 cGy

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Horse Anti-thymocyte Globulin

Regimen D

EXPERIMENTAL

Includes patients with the following specific diagnosis of: Severe Combined Immune Deficiency Syndrome with no evidence of host NK function (will receive Regimen A) and matched related donor * Cyclophosphamide (30 mg/kg total dose) * Fludarabine (90 mg/m2 total dose) * Rabbit anti-thymocyte globulin (Thymoglobulin)(TMG)\*\*(8 mg/kg total dose) TMG only in family haploidentical and unrelated donors

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Rabbit Anti-thymocyte Globulin

Interventions

Fludarabine DRUG

Also known as: Fludara®

Regimen A - Standard Conditioning Regimen; Regimen B; Regimen C; Regimen D

Cyclophosphamide DRUG

Also known as: Cytoxan®

Regimen B; Regimen C; Regimen D

Busulfan DRUG

Also known as: Busulfex®

Regimen A - Standard Conditioning Regimen

Alemtuzumab DRUG

Also known as: Campath®

Regimen A - Standard Conditioning Regimen

Rabbit Anti-thymocyte Globulin DRUG

Also known as: TMG, Thymoglobulin

Regimen B; Regimen D

Horse Anti-thymocyte Globulin DRUG

Also known as: ATG, Lymphocyte Immune Globulin

Regimen C

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must meet the eligibility criteria for organ function regardless of diagnosis:
• Age \< 30 or = 30 years of age
• Adequate renal function defined as serum creatinine \< or = 1.5 x normal, or creatinine clearance or radioisotope glomerular filtration rate (GFR) \> or =40 ml/min/m2 or \>60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range
• Adequate liver function defined as serum glutamic oxaloacetic transaminase (SGOT)(Aspartate transaminase (AST)) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) \< 5.0 x normal
• Adequate cardiac function defined as shortening fraction of \> or = 28% by echocardiogram, or ejection fraction of \> or = 48% by radionuclide angiogram or echocardiogram
• Adequate pulmonary function defined as asymptomatic or, if symptomatic, carbon monoxide diffusing capacity test (DLCO) \>45% of predicted (corrected for hemoglobin level). If unable to obtain pulmonary function test, O2 saturation \>85% in room air.
• Bone Marrow Failure Syndromes
• Patients with the following diagnoses are eligible:
• Severe Aplastic Anemia:
• Hypocellular bone marrow biopsy (\<25% cellularity) and 2/3 of the following (at diagnosis or nadir):
• Absolute Neutrophil Count (ANC) \<200/mm3,
• Platelets \<20,000/mm3
• Reticulocyte count \<60,000/mm3
• Fanconi Anemia:
• Abnormal clastogenic studies (all patients) Severe Congenital Neutropenia (Kostmann's Syndrome) Amegakaryocytic Thrombocytopenia

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Bone Marrow Failure Disorders; Osteopetrosis; Fanconi Anemia; Severe Combined Immunodeficiency

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Busulfan; Alemtuzumab; Antilymphocyte Serum; thymoglobulin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Congenital Bone Marrow Failure Syndromes; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Sera; Biological Products; Complex Mixtures

Study Officials

• James Garvin, MD, PhD

  Columbia University

  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: SPONSOR

Study Record Dates

• First Submitted: November 23, 2009
• First Posted: November 25, 2009
• Study Start: September 1, 2002
• Primary Completion: September 7, 2021
• Study Completion: September 7, 2021
• Last Updated: October 31, 2024

Record last verified: 2024-10

Locations

US (1)