- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00590460
Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia (Mafia)
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Texas Children's Hospital
-
Houston, Texas, United States, 77030
- Methodist Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single Arm Study: Stem Cell Transplant
CAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion
|
Given intravenous on days -8, -7, and -6
Other Names:
Given intravenous on days -5, -4, -3 and -2 dose is 400 micrograms/kg Given intravenous on days -8, -7, -6, -5 and -4 Dose is 30 mg/m2
Stem cells are infused on day 0
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Donor Engraftment
Time Frame: 100 Days
|
Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation
|
100 Days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Patients With Graft Failure
Time Frame: 100 days
|
Graft failure is defined as engraftment of less than 65% of donor cells 100 days after transplantation.
|
100 days
|
Patients With Treated Related Death
Time Frame: 100 days
|
Number of patients with treated related death
|
100 days
|
Days to Absolute Neutrophil Count (ANC) of 500/mm3
Time Frame: 30 Days
|
Number of days to Absolute neutrophil count (ANC) of 500/mm3
|
30 Days
|
Days to Platelet Count of 20,000/mm3 Without Transfusions
Time Frame: 30 Days
|
Number of days to Platelet count of 20,000 / mm3 without transfusions
|
30 Days
|
Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)
Time Frame: 100 days
|
Number of patients with grade II - IV acute Graft versus Host Disease (GVHD)
|
100 days
|
Number of Patients Alive at 1 Year Post Transplant
Time Frame: 1 year
|
Number of patients alive at 1 year post allogeneic stem cell transplant
|
1 year
|
Patients With Limited Chronic GVHD From Day 100 to 365
Time Frame: 365 days
|
Number of patients with limited chronic GVHD from day 100 to 365
|
365 days
|
Patients With Extensive Chronic GVHD From Day 100 to 365
Time Frame: 365 days
|
Number of patients with extensive chronic GVHD from day 100 to 365.
|
365 days
|
Patients With Grade III - IV Acute GVHD
Time Frame: 100 days
|
Number of patients with Grade III-IV acute GVHD
|
100 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Malcolm Brenner, M.B., Ph.D.,, Baylor College of Medicine
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Kidney Diseases
- Urologic Diseases
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- DNA Repair-Deficiency Disorders
- Anemia, Hypoplastic, Congenital
- Congenital Bone Marrow Failure Syndromes
- Bone Marrow Failure Disorders
- Renal Tubular Transport, Inborn Errors
- Anemia
- Fanconi Syndrome
- Fanconi Anemia
- Anemia, Aplastic
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Fludarabine
- Alemtuzumab
Other Study ID Numbers
- H-9938
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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