Cytoxan, Fludara, and Antithymocyte Globulin Conditioning Followed By Stem Cell Transplant in Treating Fanconi Anemia

NCT00630253 | Completed Phase 1 Results DMC

• 2 other identifiers: MT2000-090001M34441
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, before a donor stem cell transplant helps to remove the patient's cells to allow for the transplant cells to take and grow. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant and giving cyclosporine before and after transplant may stop this from happening. PURPOSE: This phase I/II trial is studying the side effects of cyclophosphamide, fludarabine, and antithymocyte globulin followed by donor stem cell transplant and to see how well it works in treating patients with Fanconi anemia.

Conditions

Fanconi Anemia

Keywords

Fanconi anemia

Outcome Measures

Primary Outcomes (1)

• Number of Participants Experiencing Graft Failure

  graft failure = absolute neutrophil count (ANC) \<5 x 10\^8/L and an acellular bone marrow aspirate/biopsy

  From Day 1 to event, assessed up to100 days

Secondary Outcomes (4)

• Number of Participants With Acute Graft-Versus-Host Disease (GVHD)

  Day 42

• Number of Participants Experiencing Overall Survival

  1 Year

• Number of Participants With Chronic Graft-Versus-Host Disease (GVHD)

  1 Year

• Number of Participants With Transplant Related Deaths

  Day 100

Study Arms (3)

Marrow Isolex

EXPERIMENTAL

bone marrow processed using Isolex 300i (for patients enrolled through April 2010)

Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil

UCB

EXPERIMENTAL

No processing Notes: sibling donor UCB is used as the stem cell source and co-enroll for unlicensed UCB registry

Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil

Marrow Clinimax

EXPERIMENTAL

bone marrow processed using CliniMACS (for patients enrolled beginning with the August 2010 protocol version)

Biological: Anti-Thymocyte Globulin; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Stem Cell Transplantation; Drug: Methylprednisolone; Drug: Filgrastim; Drug: Cyclosporine; Drug: Mycophenolate Mofetil

Interventions

Anti-Thymocyte Globulin BIOLOGICAL

30 mg/kg/day will be administered after MP on days -6, -5, -4, -3 and -2.

Also known as: ATG

Marrow Clinimax; Marrow Isolex; UCB

Cyclophosphamide DRUG

5 mg/kg is to be given as a 2 hour infusion, Days -6 through -3.

Also known as: Cytoxan

Marrow Clinimax; Marrow Isolex; UCB

Fludarabine DRUG

35 mg/m\^2 intravenously (IV) on days -6 through -2.

Also known as: Fludara

Marrow Clinimax; Marrow Isolex; UCB

Hematopoietic Stem Cell Transplantation PROCEDURE

Bone marrow or umbilical cord blood infusion on day 0.

Also known as: HSCT

Marrow Clinimax; Marrow Isolex; UCB

Methylprednisolone DRUG

Methylprednisolone (MP) 2 mg/kg/day intravenously every 24 hours will be given from day -6 until day -2 as a premedication for ATG.

Also known as: MP

Marrow Clinimax; Marrow Isolex; UCB

Filgrastim DRUG

5 mcg/kg per day intravenously (IV) continue until Absolute neutrophil count \> or = 2.5 x 10\^9/L

Also known as: G-CSF

Marrow Clinimax; Marrow Isolex; UCB

Cyclosporine DRUG

Cyclosporine IV over 2 hours or orally every 8-12 hours beginning on day -3 and continuing until day 100, followed by a taper.

Also known as: CSA

Marrow Clinimax; Marrow Isolex; UCB

Mycophenolate Mofetil DRUG

Day -3 through day +30 or for 7 days after engraftment, whichever day is later, if no acute GVHD. Engraftment is defined as 1st day of 3 consecutive days of absolute neutrophil count \[ANC\] \> 0.5 x 10\^9/L. MMF will be given at a dose of 15 mg/kg/dose every 8 hours PO (to a maximum dose of 1 gram).

Also known as: MMF

Marrow Clinimax; Marrow Isolex; UCB

Eligibility Criteria

• Age: Up to 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be \<60 years of age with a diagnosis of Fanconi Anemia (FA).
• Patients must have an HLA-A, B, DRB1 identical sibling donor. Patients and donors will be typed for HLA-A and B using serological or molecular techniques and for DRB1 using high resolution molecular typing.
• Patients with FA must have moderately severe aplastic anemia (AA), early myelodysplastic syndrome (MDS) with no excess blasts with or without chromosomal abnormalities.
• In patients \<18 years of age, moderately severe aplastic anemia is defined as having at least one of the following:
• platelet count \<40 x 10\^9/L
• absolute neutrophil count (ANC) \<10 x 10\^8/L
• Hgb \<9 g/dL
• In patients 18-60 years of age, moderately severe aplastic anemia is defined as having at least one of the following:
• platelet count \<20 x 10\^9/L
• absolute neutrophil count ANC \<5 x 10\^8/L
• Hgb \<8 g/dL
• Early myelodysplastic syndrome, with multilineage dysplasia with \< 5% blasts, with or without chromosomal anomalies.
• Adequate major organ function including:
• Cardiac: ejection fraction \>45%
• Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites)

You may not qualify if:

• Active bacterial infection within one week of hematopoietic cell transplant (HCT)
• Active fungal infection at time of HCT.
• Late MDS with greater than 5% blasts in bone marrow.
• Acute myelogenous leukemia (AML) or history of AML
• Malignant solid tumor (e.g. squamous cell carcinoma of the head/neck/cervix) within 2 years of HCT.
• Pregnant or 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; Cyclophosphamide; fludarabine; fludarabine phosphate; Hematopoietic Stem Cell Transplantation; Methylprednisolone; Filgrastim; Granulocyte Colony-Stimulating Factor; Cyclosporine; Mycophenolic Acid

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

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 L. MacMillan, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2008
• First Posted: March 6, 2008
• Study Start: February 17, 2000
• Primary Completion: October 10, 2020
• Study Completion: October 10, 2020
• Last Updated: October 12, 2021
• Results First Posted: October 12, 2021

Record last verified: 2021-10

Locations

US (1)