Trial record 6 of 61 for:    "Fanconi anemia"

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

This study has been terminated.
(slow accrual)
Sponsor:
Collaborators:
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Malcolm Brenner, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00590460
First received: December 26, 2007
Last updated: November 21, 2013
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Fanconi Anemia
Severe Aplastic Anemia
Biological: CAMPATH-1H
Biological: Anti-CD45
Drug: Fludarabine
Procedure: Stem cell infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cd45 (Yth-24 and Yth 54) and Cd52 (Campath-1H) Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients With Fanconi Anemia

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Number of Patients With Donor Engraftment [ Time Frame: 100 Days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Patients With Graft Failure [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Number of Patients With Treated Related Death [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
  • Days to Absolute Neutrophil Count (ANC) of 500/mm3 [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
  • Days to Platelet Count of 20,000/mm3 Without Transfusions [ Time Frame: 30 Days ] [ Designated as safety issue: No ]
  • Number of Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD) [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

    Graft versus Host Disease is when the new stem cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, the liver and the intestines.

    The grades of Graft versus Host disease are based on how much the patient's body is damaged by the stem cells attacking the organs. In general the grading ranges from grade I (minor) to grade IV (severe).


  • Number of Patients Alive at 1 Year Post Transplant [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Number of Patients With Limited Chronic GVHD From Day 100 to 365 [ Time Frame: 365 days ] [ Designated as safety issue: Yes ]

    Graft versus Host Disease is when the new stem cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, the liver and the intestines.

    Chronic GVHD usually occurs later than acute GVHD. It usually occurs at least one year after the transplant. Limited chronic GVHD is when the damage is less extensive to the body.


  • Number of Patients With Extensive Chronic GVHD From Day 100 to 365 [ Time Frame: 365 days ] [ Designated as safety issue: Yes ]

    Graft versus Host Disease is when the new stem cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, the liver and the intestines.

    Chronic GVHD usually occurs later than acute GVHD. It usually occurs at least one year after the transplant. Extensive chronic GVHD is when the damage is more extensive to the body.


  • Number of Patients With Grade III - IV Acute GVHD [ Time Frame: 100 ] [ Designated as safety issue: Yes ]

    Graft versus Host Disease is when the new stem cells (graft) recognize that the body tissues of the patient (host) are different from those of the donor. When this happens, cells in the graft may attack the host organs, primarily the skin, the liver and the intestines.

    The grades of Graft versus Host disease are based on how much the patient's body is damaged by the stem cells attacking the organs. In general the grading ranges from grade I (minor) to grade IV (severe).



Enrollment: 5
Study Start Date: July 2001
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: single group Biological: CAMPATH-1H
Given intravenous on days -8, -7, and -6
Other Name: Alemtuzumab
Biological: Anti-CD45

Given intravenous on days -5, -4, -3 and -2

dose is 400 micrograms/kg

Drug: Fludarabine

Given intravenous on days -8, -7, -6, -5 and -4

Dose is 30 mg/m2

Procedure: Stem cell infusion
Stem cells are infused on day 0

Detailed Description:

If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftment/rejection is followed by failure to undergo autologous reconstitution.

For HLA Mismatched donors, harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system.

Fludarabine will be given as 5 daily intravenous infusions. Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion. Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion.

Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -6 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -5 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 -4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 -3 YTH 24/54 400ug/kg over 6 hr -2 YTH 24/54 400ug/kg over 6 hr -1 -0 Stem Cell Infusion

GVHD prophylaxis will be achieved through positive selection for CD34 resulting in > 3 log T cell depletion. Previous reports have indicated that there is a low frequency of severe (Grade II/IV) GvHD after haploidentical transplants if recipients receive stem cell populations containing <5 x 10e4 CD3 positive T cells. We hope to achieve such levels with our CD34 enrichment protocol. However, pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3+ve T cells/kg recipient weight. In addition, Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity, in vivo.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00590460

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Methodist Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Baylor College of Medicine
Texas Children's Hospital
The Methodist Hospital System
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Malcolm Brenner, M.B., Ph.D., Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Malcolm Brenner, Professor, Director Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00590460     History of Changes
Obsolete Identifiers: NCT00058565
Other Study ID Numbers: H-9938
Study First Received: December 26, 2007
Results First Received: July 2, 2012
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Baylor College of Medicine:
Allogeneic Stem Cell Transplant
Fanconi Anemia
Severe Aplastic Anemia
fludarabine
campath
anti-CD45

Additional relevant MeSH terms:
Fanconi Anemia
Fanconi Syndrome
Anemia
Anemia, Aplastic
Hematologic Diseases
Bone Marrow Diseases
Anemia, Hypoplastic, Congenital
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Antibodies, Monoclonal
Fludarabine monophosphate
Campath 1G
Fludarabine
Alemtuzumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 23, 2014