Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia

NCT00590460 | Terminated Phase 1 Results DMC

• 1 other identifier: H-9938
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to discover whether children and adults with Fanconi anemia (FA) can be safely and effectively transplanted with Human Leukocyte Antigen (HLA) mismatched (up to one haplotype), HLA-matched sibling, or unrelated donor stem cells, when leukocytolytic monoclonal antibodies are the sole conditioning agents (patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen). Three monoclonal antibodies (MAb) will be used in combination. Two of them, YTH 24 and YTH 54 are rat antibodies directed against two contiguous epitopes on the CD45 (common leucocyte) antigen. They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts (HLA matched and mismatched) at this center. They produce a transient depletion of \>90% circulating leucocytes. The third MAb is Campath 1H, a humanized rat anti-CD52 MAb. This MAb has been widely used to treat B cell chronic lymphocytic leukemia (B-CLL) and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease. Because these MAb produce both profound immunosuppression and significant, though transient, myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia, in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity. We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity. Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial graft versus host disease (GvHD) prophylaxis. Additional GvHD prophylaxis will be provided by administration of the medication FK506.

Conditions

Fanconi Anemia; Severe Aplastic Anemia

Keywords

Allogeneic Stem Cell Transplant; Fanconi Anemia; Severe Aplastic Anemia; fludarabine; campath; anti-CD45

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Donor Engraftment

  Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation

  100 Days

Secondary Outcomes (9)

• Number of Patients With Graft Failure

  100 days

• Patients With Treated Related Death

  100 days

• Days to Absolute Neutrophil Count (ANC) of 500/mm3

  30 Days

• Days to Platelet Count of 20,000/mm3 Without Transfusions

  30 Days

• Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)

  100 days

Study Arms (1)

Single Arm Study: Stem Cell Transplant

EXPERIMENTAL

CAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion

Biological: CAMPATH-1H; Biological: Anti-CD45; Drug: Fludarabine; Procedure: Stem cell infusion

Interventions

CAMPATH-1H BIOLOGICAL

Given intravenous on days -8, -7, and -6

Also known as: Alemtuzumab

Single Arm Study: Stem Cell Transplant

Anti-CD45 BIOLOGICAL

Given intravenous on days -5, -4, -3 and -2 dose is 400 micrograms/kg

Single Arm Study: Stem Cell Transplant

Fludarabine DRUG

Given intravenous on days -8, -7, -6, -5 and -4 Dose is 30 mg/m2

Single Arm Study: Stem Cell Transplant

Stem cell infusion PROCEDURE

Stem cells are infused on day 0

Single Arm Study: Stem Cell Transplant

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Fanconi Anemia or other suspected DNA breakage/chromosomal instability syndromes, such as dyskeratosis congenita or Nijmegen breakage syndrome of all ages are eligible.
• Diagnosis of Fanconi anemia confirmed by studies of peripheral blood or bone marrow sensitivity to mitomycin C or DEB or clinical evidence of other DNA breakage/chromosomal instability syndrome as determined by genetic testing or clinical diagnosis by a geneticist
• Severe aplasia anemia as evidenced by a hypocellular bone marrow and at least 1 of the 3 criteria below: ANC \< 500/mm3 Hemoglobin \< 10 gm/dl with reticulocyte count \< 1% Platelet count \< 50,000/mm3
• Availability of an HLA matched or mismatched (up to one haplotype) family member who has been documented not to have Fanconi anemia or of an unrelated HLA matched stem cell donor. Fully matched is defined at 6/6 match by high resolution DR based DNA typing.
• Life expectancy greater than 6 weeks limited by diseases other than FA
• Creatinine 2X normal for age or less
• Karnofsky score 70% or more

You may not qualify if:

• Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram (i.e., shortening fraction less than 25%).
• Patients with known allergy to rat serum products.
• Patients with a severe infection that on evaluation by the Principal Investigator precludes ablative chemotherapy or successful transplantation.
• Patients with severe personality disorder or mental illness.
• Patients with documented HIV positivity.
• Pregnant
• NOTE: Patients who would be excluded from the protocol strictly for laboratory abnormalities can be included at the investigator's discretion after approval by the CCGT Protocol Review Committee and the FDA Reviewer.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• The Methodist Hospital Research Institute: collaborator
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (2)

Methodist Hospital

Houston, Texas, 77030, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Fanconi Anemia; Anemia, Aplastic

Interventions

Alemtuzumab; fludarabine

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; 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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Malcolm Brenner, MD
• Organization: BAYLOR

mbrenner@bcm.edu

832-824-4663

Study Officials

• Malcolm Brenner, M.B., Ph.D.,

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Director Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: January 10, 2008
• Study Start: July 1, 2001
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: May 24, 2018
• Results First Posted: August 9, 2012

Record last verified: 2018-04

Locations

US (2)