Lymphoma
Conditions
Keywords
angioimmunoblastic T-cell lymphoma
Brief summary
RATIONALE: Cyclosporine may help the immune system slow the growth of angioimmunoblastic T-cell lymphoma. PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients with recurrent or refractory angioimmunoblastic T-cell lymphoma.
Detailed description
OBJECTIVES: Primary * Determine the response rate (complete and partial) in patients with recurrent or refractory angioimmunoblastic T-cell lymphoma treated with cyclosporine. Secondary * Determine the disease-free, progression-free, and overall survival of patients treated with this drug. * Determine the toxicity of this drug in these patients. OUTLINE: Patients receive oral cyclosporine twice daily for up to 36 weeks in the absence of unacceptable toxicity or disease progression during weeks 1-6. Patients experiencing disease progression during weeks 7-36, receive an additional 36 weeks of therapy. Patients are followed every 3 months for 2 years and then every 6 months for 1 year. PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study within 2.5 years.
Interventions
DRUGcyclosporine
Cyclosporine doses will be based on actual body weight unless actual body weight is \> 15 kg higher than the ideal body weight. Cyclosporine dose will be adjusted to maintain a trough whole blood level of 250-450 ng/mL during the high dose period (weeks 1 -6, starting dose will begin at cyclosporine 3 mg/kg by mouth two times a day (PO BID)) and 150-250 ng/mL during the maintenance period (weeks 7-36, maintenance dose will begin at cyclosporine 2 mg/kg PO BID) in the absence of renal toxicity
Sponsors
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of angioimmunoblastic T-cell lymphoma (recurrent or refractory) based on histologic examination. * At least one objective measurable or evaluable disease parameter. * Have failed at least one type of treatment: chemotherapy, auto-transplant, or steroid treatment. Patients may not receive concurrent chemotherapy. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Adequate renal function as indicated by creatinine \<= 1.5 the upper limit of normal (ULN). * Adequate liver function as indicated by alkaline phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) \<= 2x the upper limit of normal. * Total bilirubin \<= 2x the upper limit of normal. * Age 18 or older.
Exclusion criteria
* Prior cyclosporine or Tacrolimus (FK506). * Prior allogeneic transplant. * Evidence of active infection. * Congestive heart failure, kidney failure, liver failure, or other severe co-morbidities. * Evidence of active neurological impairment. * Previous history of hypersensitivity to cyclosporine and/or Cremorphor EL (polyoxyethylated oil). * History of other malignancies (other than cured carcinomas in situ of the cervix or basal cell carcinoma of the skin). * pregnant or breastfeeding women. * Human immunodeficiency virus (HIV) positive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete and Partial Response) | Assessed at weeks 6, 12, 24 and 36 from onset of treatment, and then at 1 year, 18 months, 2 years and 3 years from registration during follow-up. | Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma. Response included complete response and partial response. Complete response was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization of those biochemical abnormalities definitely attributed to NHL. All lymph nodes and nodal masses must have regressed to normal size. Partial response was defined as a decrease of \> 50% in the SPD (sum of the products of the diameters) of the six largest (or less) dominant nodes or nodal masses, no increase in the size of the liver or the spleen, and no new sites of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Assessed every 3 months for 2 years, then every 6 months for 1 year. | Overall survival was defined as time from randomization to death from any cause. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from ECOG member institutions between September 2, 2005 and March 24, 2009. The first patient was accrued on January 24, 2006. The study was terminated due to slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporine | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Step 1 | Adverse Event | 1 |
| Step 1 | Withdrawal by Subject | 1 |
| Step 2 | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Cyclosporine |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 4 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 2 / 3 |
Outcome results
Primary
Response Rate (Complete and Partial Response)
Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma. Response included complete response and partial response. Complete response was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization of those biochemical abnormalities definitely attributed to NHL. All lymph nodes and nodal masses must have regressed to normal size. Partial response was defined as a decrease of \> 50% in the SPD (sum of the products of the diameters) of the six largest (or less) dominant nodes or nodal masses, no increase in the size of the liver or the spleen, and no new sites of disease.
Time frame: Assessed at weeks 6, 12, 24 and 36 from onset of treatment, and then at 1 year, 18 months, 2 years and 3 years from registration during follow-up.
Population: all 4 enrolled patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclosporine | Response Rate (Complete and Partial Response) | 0.25 Proportion of participants |
Secondary
Overall Survival
Overall survival was defined as time from randomization to death from any cause.
Time frame: Assessed every 3 months for 2 years, then every 6 months for 1 year.
Population: all 4 enrolled patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cyclosporine | Overall Survival | 36 Months |