search
Back to results

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

Primary Purpose

Fanconi Anemia, Severe Aplastic Anemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CAMPATH-1H
Anti-CD45
Fludarabine
Stem cell infusion
Sponsored by
Baylor College of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fanconi Anemia focused on measuring Allogeneic Stem Cell Transplant, Fanconi Anemia, Severe Aplastic Anemia, fludarabine, campath, anti-CD45

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Methodist Hospital
  • Texas Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single Arm Study: Stem Cell Transplant

Arm Description

CAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion

Outcomes

Primary Outcome Measures

Number of Patients With Donor Engraftment
Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation

Secondary Outcome Measures

Number of Patients With Graft Failure
Graft failure is defined as engraftment of less than 65% of donor cells 100 days after transplantation.
Patients With Treated Related Death
Number of patients with treated related death
Days to Absolute Neutrophil Count (ANC) of 500/mm3
Number of days to Absolute neutrophil count (ANC) of 500/mm3
Days to Platelet Count of 20,000/mm3 Without Transfusions
Number of days to Platelet count of 20,000 / mm3 without transfusions
Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)
Number of patients with grade II - IV acute Graft versus Host Disease (GVHD)
Number of Patients Alive at 1 Year Post Transplant
Number of patients alive at 1 year post allogeneic stem cell transplant
Patients With Limited Chronic GVHD From Day 100 to 365
Number of patients with limited chronic GVHD from day 100 to 365
Patients With Extensive Chronic GVHD From Day 100 to 365
Number of patients with extensive chronic GVHD from day 100 to 365.
Patients With Grade III - IV Acute GVHD
Number of patients with Grade III-IV acute GVHD

Full Information

First Posted
December 26, 2007
Last Updated
April 26, 2018
Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
search

1. Study Identification

Unique Protocol Identification Number
NCT00590460
Brief Title
Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
Acronym
Mafia
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Terminated
Why Stopped
slow accrual
Study Start Date
July 2001 (undefined)
Primary Completion Date
September 2009 (Actual)
Study Completion Date
September 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
Collaborators
The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fanconi Anemia, Severe Aplastic Anemia
Keywords
Allogeneic Stem Cell Transplant, Fanconi Anemia, Severe Aplastic Anemia, fludarabine, campath, anti-CD45

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Single Arm Study: Stem Cell Transplant
Arm Type
Experimental
Arm Description
CAMPATH-1H Anti-CD45 Fludarabine Stem Cell Infusion
Intervention Type
Biological
Intervention Name(s)
CAMPATH-1H
Other Intervention Name(s)
Alemtuzumab
Intervention Description
Given intravenous on days -8, -7, and -6
Intervention Type
Biological
Intervention Name(s)
Anti-CD45
Intervention Description
Given intravenous on days -5, -4, -3 and -2 dose is 400 micrograms/kg
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Given intravenous on days -8, -7, -6, -5 and -4 Dose is 30 mg/m2
Intervention Type
Procedure
Intervention Name(s)
Stem cell infusion
Intervention Description
Stem cells are infused on day 0
Primary Outcome Measure Information:
Title
Number of Patients With Donor Engraftment
Description
Number of patients with engraftment of at least 65% of donor cells 100 days after transplantation
Time Frame
100 Days
Secondary Outcome Measure Information:
Title
Number of Patients With Graft Failure
Description
Graft failure is defined as engraftment of less than 65% of donor cells 100 days after transplantation.
Time Frame
100 days
Title
Patients With Treated Related Death
Description
Number of patients with treated related death
Time Frame
100 days
Title
Days to Absolute Neutrophil Count (ANC) of 500/mm3
Description
Number of days to Absolute neutrophil count (ANC) of 500/mm3
Time Frame
30 Days
Title
Days to Platelet Count of 20,000/mm3 Without Transfusions
Description
Number of days to Platelet count of 20,000 / mm3 without transfusions
Time Frame
30 Days
Title
Patients With Grade II - IV Acute Graft Versus Host Disease (GVHD)
Description
Number of patients with grade II - IV acute Graft versus Host Disease (GVHD)
Time Frame
100 days
Title
Number of Patients Alive at 1 Year Post Transplant
Description
Number of patients alive at 1 year post allogeneic stem cell transplant
Time Frame
1 year
Title
Patients With Limited Chronic GVHD From Day 100 to 365
Description
Number of patients with limited chronic GVHD from day 100 to 365
Time Frame
365 days
Title
Patients With Extensive Chronic GVHD From Day 100 to 365
Description
Number of patients with extensive chronic GVHD from day 100 to 365.
Time Frame
365 days
Title
Patients With Grade III - IV Acute GVHD
Description
Number of patients with Grade III-IV acute GVHD
Time Frame
100 days

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm Brenner, M.B., Ph.D.,
Organizational Affiliation
Baylor College of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs