Aplastic Anemia
Conditions
Brief summary
RATIONALE: Immunosuppressive therapies, such as anti-thymocyte globulin and cyclosporine, may improve bone marrow function and increase blood cell counts. PURPOSE: This phase II trial is studying how well giving anti-thymocyte globulin together with cyclosporine as first-line therapy works in treating patients with severe aplastic anemia.
Detailed description
PRIMARY OBJECTIVES: To determine the response rate of r-ATG and CsA in the first line setting. SECONDARY OBJECTIVES: To determine the level of IS as assessed by Immuknow assay in responders and compare it to non-responders. OUTLINE:Patients receive anti-thymocyte globulin IV over 4-24 hours daily on days 1-5. Beginning on day 6, patients receive oral cyclosporine twice daily for 6 months followed by a taper. Treatment continues in the absence of disease progression or unacceptable toxicity.
Interventions
BIOLOGICALanti-thymocyte globulin
Given IV
DRUGcyclosporine
Given orally
Sponsors
The Cleveland Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients with sAA as defined by Camitta who are candidates for IS therapy; these criteria include bone marrow cellularity \< 25% or 25-50% with \< 30% of hematopoietic cells; it should also have two of the following three parameters: peripheral blood neutrophils \< 0.5 x 10\^9/L, platelets \< 20 x 10\^9/L and reticulocytes \< 60 x 10\^9/L in anemic patients * If cytogenetic testing has been done, it should show normal karyotype or be not informative * Patients should be either unwilling or otherwise ineligible (age, comorbidities, lack of donor) for bone marrow transplantation as a therapeutic modality * Not previously treated with ATG for sAA * Patients must have ECOG performance status of 0, 1, or 2 * Vitamin B12 and folic acid deficiency must be ruled out by measurement of serum levels * Patients must have had a bone marrow biopsy examination in the three months prior to enrolling in the study * Must be able to provide informed consent * Systemic and other hematologic causes of pancytopenia, based on clinical presentation, must have been ruled out
Exclusion criteria
* Patients with clinically evident congestive heart failure, serious cardiac arrhythmias; symptoms of coronary artery disease must be cleared by cardiology prior to therapy * Patients who have had chemotherapy, radiotherapy, or immunotherapy or other investigational drug use within 3 weeks prior to study entry * Pregnant women * All females of childbearing potential must have a blood test or urine study within two weeks prior to induction registration to rule out pregnancy * Women of childbearing potential are strongly advised to use an accepted and effective method of contraception * Patients who have medical, psychological, or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patients Treated With Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) and Cyclosporine (CsA) Achieving at Least a Partial Remission (PR) at 6 Months | At 6 months | Patients will be classified as responders if they have transfusion independence and meet two of the following three criteria: ANC greater than 500/mm3; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3. Transfusion independence is defined as no need for transfusions for one month prior to response assessment. |
Countries
United States
Participant flow
Recruitment details
Patients with severe aplastic anemia were recruited over a period of four years (2005-2009) in the hematology clinic at the Cleveland Clinic, a hospital in Cleveland, Ohio.
Participants by arm
| Arm | Count |
|---|---|
| rATG Patients receive anti-thymocyte globulin IV daily over 4-24 hours on days 1-5. Beginning on day 6, patients receive oral cyclosporine twice daily for 6 months followed by a taper. Treatment continues in the absence of disease progression or unacceptable toxicity | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | rATG |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 51.95 years STANDARD_DEVIATION 18.43 |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 11 / 20 |
Outcome results
Primary
Patients Treated With Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) and Cyclosporine (CsA) Achieving at Least a Partial Remission (PR) at 6 Months
Patients will be classified as responders if they have transfusion independence and meet two of the following three criteria: ANC greater than 500/mm3; platelet count greater than 20,000/mm3; and reticulocyte count greater than 40,000/mm3. Transfusion independence is defined as no need for transfusions for one month prior to response assessment.
Time frame: At 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) | Patients Treated With Rabbit Antithymocyte Globulin (r-ATG/Thymoglobulin) and Cyclosporine (CsA) Achieving at Least a Partial Remission (PR) at 6 Months | 9 participants |