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ICH GCP | Clinical Trials Registry

Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia



Sponsors

Lead Sponsor

 M.D. Anderson Cancer Center


Source

M.D. Anderson Cancer Center

Oversight Info

Has Dmc

No


Brief Summary

Primary Objectives: 1. To determine the feasibility and toxicity of employing purine-analog based conditioning for allogeneic donor stem cell transplantation in patients with severe aplastic anemia (AA). 2. To determine the engraftment kinetics and degree of chimerism that can be achieved with this strategy.

Detailed Description

Before treatment starts, patients will have their bone marrow checked and will have lung, heart, and kidney tests. Patients in this study will receive the drugs fludarabine, cyclophosphamide, and antithymocyte globulin by vein through a previously inserted plastic catheter that extends into the large chest vein. Fludarabine will be given daily for four days, cyclophosphamide will given daily for four days, and antithymocyte globulin will be given daily for four days (three days for related donor transplants). Two days after the last dose of cyclophosphamide, donor marrow or stem cells will be infused through a catheter (thin plastic tube). Drugs will be given to lower the chance of an allergic reaction to the stem cells. Patients will also get shots of filgrastim (a drug that helps white blood cell growth) and antibiotics by mouth. The blood cell counts will fall to low levels during the first 2 weeks when patients may need transfusions of red blood cells and platelets. The chemotherapy will be given in the hospital. After the infusion of stem cells, patients will be monitored in the hospital. They will later be closely followed as outpatients and will be required to remain in the Houston area for about three months after the transplant. Drugs (cyclosporine and methotrexate) to lower the chance of graft-versus-host disease will be given. Cyclosporine will be given as a continuous infusion starting 2 days before transplantation. Methotrexate will be given through the catheter on Days 1, 3, 6 and 11 after transplantation. Cyclosporine will be given as pills when the patient is able to swallow. Cyclosporine will be continued for no less than 6 months after transplantation after which it will be gradually stopped. The drug tacrolimus may be used instead of cyclosporine. Blood, urine, bone marrow, and x-ray exams will be done as needed to monitor the results of bone marrow transplantation. Patients may require blood and platelet transfusions. Blood tests will be done daily while hospitalized and several times a week until the blood counts recover. Bone marrow aspiration and biopsies will be performed before the transplant, when the donated cells show signs of engraftment, and at other times during the next 1 to 3 years. They will be done to evaluate the growth of the transplant marrow, possible recurrence of malignancy, and recovery of immunity. If this treatment proves unsuccessful in more than three of the first ten patients, the study will be stopped. This is an investigational study. The FDA has approved all of the drugs in this study for other indications. Up to 30 patients will be treated on this study. All will be enrolled at M.D. Anderson.

Overall Status

Completed

Start Date

2000-12-01

Completion Date

2009-08-01

Primary Completion Date

2009-08-01

Phase

N/A

Study Type

Interventional

Primary Outcome

Measure

Time Frame

Number of Patients With Engraftment Response
First 100 days post transplant.

Enrollment

9

Condition

 Aplastic Anemia

Intervention

Intervention Type

Drug

Intervention Name

 Fludarabine

Description

30 mg/m^2 by vein daily over 30 minutes

Arm Group Label

Fludarabine + Cyclophosphamide + ATG

Other Name

Fludarabine Phosphate

Fludara



Intervention Type

Drug

Intervention Name

 Cyclophosphamide

Description

300 mg/m^2 by vein daily over 2 hours

Arm Group Label

Fludarabine + Cyclophosphamide + ATG

Other Name

Cytoxan

Neosar



Intervention Type

Drug

Intervention Name

 Antithymocyte Globulin

Description

3.75 mg/kg by vein daily over 4 hours

Arm Group Label

Fludarabine + Cyclophosphamide + ATG

Other Name

ATG

Thymoglobulin




Eligibility

Criteria

Inclusion Criteria: - Patients up to 70 years of age with a diagnosis of severe AA (Camitta et al., 1979) and a matched unrelated donor who are unresponsive to IS or who have relapsed after an initial response to IS. Patients with a diagnosis of SAA and an human leukocyte antigen (HLA) - compatible sibling donor are eligible only if they are 40 years of age or older (up to age 70) and regardless whether they have received IS or not. Patients with primary or secondary graft failure following autologous or allogeneic stem cell transplant are eligible. - Patients must have a serum bilirubin of 2 mg/dl or less, serum creatinine < 2.0 mg/dl, no symptomatic cardiac or pulmonary disease and a PS of no more than 2. Life expectancy not severely limited by concomitant illness (> 12 weeks). Left ventricular ejection fraction > 40%, no uncontrolled arrhythmia or symptomatic cardiac disease. Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) > 40%. No symptomatic pulmonary disease. Negative pregnancy test. - Patients must have an HLA-compatible related or unrelated donor willing to donate marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 and DQB1 ("10 of 10 match") is preferred. However, a one-antigen mismatch ("micromismatch") is also considered acceptable matching ("9 of 10 match"). - Patients must sign informed consent. In the event of a pediatric patient (i.e., a minor), consent will be provided by their guardian/parent. - Lack of clonal cytogenetic abnormalities associated with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) or other hematologic malignancies. Exclusion Criteria: - Life expectancy of less than 8 weeks. Inability to provide informed consent.

Gender

All

Minimum Age

N/A

Maximum Age

70 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Paolo Anderlini, MD
Principal Investigator
M.D. Anderson Cancer Center

Location

Facility

U.T.M.D. Anderson Cancer Center
Houston Texas 77030 United States

Location Countries

Country

United States


Verification Date

2011-09-01

Lastchanged Date

N/A

Firstreceived Date

N/A

Responsible Party

Responsible Party Type

Sponsor


Keywords

 Severe Aplastic Anemia,  Bone Marrow Failure,  Stem Cell Transplantation,  Fludarabine,  Cyclophosphamide,  Antithymocyte Globulin,  SAA,  ATG,  Cytoxan,  Neosar,  Fludarabine Phosphate,  Thymoglobulin

Has Expanded Access

No

Condition Browse

 Anemia,  Anemia, Aplastic

Number Of Arms

1

Intervention Browse

Mesh Term

Cyclophosphamide

Fludarabine phosphate

Thymoglobulin

Antilymphocyte Serum

Fludarabine

Vidarabine



Arm Group

Arm Group Label

Fludarabine + Cyclophosphamide + ATG

Arm Group Type

Experimental

Description

Fludarabine 30 mg/m^2/day by vein (IV), Cyclophosphamide IV 300 mg/m^2/day, ATG (Antithymocyte Globulin) IV 3.75 mg/kg/day


Firstreceived Results Date

N/A

Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Non-Randomized

Intervention Model

Single Group Assignment

Primary Purpose

Treatment

Masking

None (Open Label)


Study First Submitted

January 25, 2007

Study First Submitted Qc

January 26, 2007

Study First Posted

January 29, 2007

Last Update Submitted

September 20, 2011

Last Update Submitted Qc

September 20, 2011

Last Update Posted

October 27, 2011

Results First Submitted

September 20, 2011

Results First Submitted Qc

September 20, 2011

Results First Posted

October 27, 2011


ClinicalTrials.gov processed this data on August 29, 2018

Conditions

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Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.

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