Hematopoietic Stem Cell Transplantation in High Risk Patients With Fanconi Anemia

NCT00258427 | Completed Phase 2 Results DMC

• 3 other identifiers: 2002LS014MT2002-020202M18741
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: A bone marrow or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Giving combination chemotherapy before a donor stem cell transplant may make the transplant more likely to work. This may be an effective treatment for patients with high risk Fanconi's anemia. PURPOSE: This clinical trial is studying how well combination chemotherapy works in treating high risk patients who are undergoing a donor stem cell transplant for Fanconi's anemia.

Conditions

Fanconi Anemia

Keywords

Fanconi anemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Graft Failure

  Graft failure is defined as absolute neutrophil count( ANC ) \<5 x 10\^8/L by day 30.

  Day 30

Secondary Outcomes (7)

• Number of Participants Experiencing Chronic Graft-Versus-Host Disease

  Day 42

• Number of Participants Experiencing Chronic Graft-Versus-Host Disease

  1 year

• Number of Participants Experiencing Acute Graft-Versus-Host Disease

  1 year

• Number of Participants Experiencing Acute Graft-Versus-Host Disease

  Day 42

• Number of Participants Experiencing Relapse

  1 Year

Study Arms (4)

Marrow Isolex

EXPERIMENTAL

Bone marrow processed using Isolex300i

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation

USB arm

EXPERIMENTAL

No processing

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation

Marrow Clinimacs

EXPERIMENTAL

Bone marrow processed using CliniMACS system

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation

Sibling without CliniMacs

EXPERIMENTAL

Sibling donor without the use of CliniMACS system

Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: busulfan; Drug: cyclophosphamide; Drug: fludarabine phosphate; Drug: methylprednisolone; Biological: Hematopoietic stem cell transplantation

Interventions

anti-thymocyte globulin BIOLOGICAL

Given 15 mg/kg/day intravenously every 12 hours on Days -5 through -1.

Also known as: ATG

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

filgrastim BIOLOGICAL

given 5 mcg/kg/day intravenously on Day 1 (continue until absolute neutrophil count (ANC) ≥2.5 x 10\^9/L)

Also known as: G-CSF

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

busulfan DRUG

Busulfan 0.8 mg/kg intravenously (IV) every 12 hours on Days -7 and -6 (1.0 mg/kg IV if \<4 years old)

Also known as: Busulfex

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

cyclophosphamide DRUG

10 mg/kg intravenously (IV) on Days -5 through -2.

Also known as: Cytoxan

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

fludarabine phosphate DRUG

35 mg/m\^2 intravenously (IV) on Days -5 through -2.

Also known as: Fludara

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

methylprednisolone DRUG

1 mg/kg intravenously (IV) every 12 hours on Days -5 through -1.

Also known as: Medrol

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

Hematopoietic stem cell transplantation BIOLOGICAL

Infused on Day 0 - Donor bone marrow or umbilical cord blood will be collected in the usual sterile manner using established parameters determined by the National Marrow Donor Program.

Also known as: HSCT

Marrow Clinimacs; Marrow Isolex; Sibling without CliniMacs; USB arm

Eligibility Criteria

• Age: Up to 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \<45 years of age with a diagnosis of Fanconi anemia with:
• Biallelic BRCA2 mutations, or
• Aplastic anemia, or advanced myelodysplastic syndrome (MDS) (MDS with ≥5% blasts), or acute leukemia who are ineligible for total body irradiation. Aplastic anemia is defined as having at least one of the following (with or without cytogenetic abnormalities): platelet count \<20 \* 10\^9, - absolute neutrophil count (ANC) \<5 \* 10\^8/L, - Hgb \<8 g/dL
• Patients must have an HLA-A, B, DRB1 identical or 1 antigen mismatched related or unrelated BM donor or have an HLA-A, B, DRB1 identical, 1 antigen or 2 antigen mismatched related or unrelated umbilical cord blood (UCB) donor. Patients and donors will be typed for HLA-A and B using serological level typing and for DRB1 using high resolution molecular typing.
• Adequate major organ function including:
• Cardiac: ejection fraction \>45%
• Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites, no cirrhosis)
• Karnofsky performance status \>70% or Lansky \>50%
• Women of child bearing potential must be using adequate birth control and have a negative pregnancy test.

You may not qualify if:

• Active CNS leukemia at time of HSCT.
• Active uncontrolled infection within one week of hematopoietic stem cell transplant (HSCT).
• Pregnant or lactating female.
• Donor must be in good health based on review of systems and results of physical examination.
• Donor must have a normal hemoglobin, white count, platelet count and partial thromboplastin time (PTT), and a negative diepoxybutane (DEB) test.
• HIV-NAT negative, HTLV-1, HTLV-2 negative, Hepatitis B and C negative.
• Female donors of childbearing potential must have a negative pregnancy test.
• Unrelated donors must agree to peripheral blood stem cell (PBSC) donation
• Donor is a lactating female.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Fanconi Anemia

Interventions

Antilymphocyte Serum; Filgrastim; Granulocyte Colony-Stimulating Factor; Busulfan; Cyclophosphamide; fludarabine phosphate; Methylprednisolone; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Margaret L. MacMillan, M.D.
• Organization: Masonic Cancer Center, University of Minnesota

macmi002@umn.edu

612-273-2800

Study Officials

• Margaret MacMillan, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2005
• First Posted: November 24, 2005
• Study Start: March 26, 2002
• Primary Completion: October 10, 2020
• Study Completion: October 10, 2020
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Locations

US (1)