Chronic Lymphocytic Leukemia, Leukemia
Conditions
Keywords
5-Aza, Azacytidine, Vidaza, CLL, Chronic Lymphocytic Leukemia, Richter's transformation, Leukemia
Brief summary
The objective of this study is to determine the safety and efficacy of Azacytidine in fludarabine-resistant chronic lymphocytic leukemia (CLL), Richter's transformation, and T-cell prolymphocytic leukemia (T-PLL).
Detailed description
Azacytidine is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the bad genes, the tumor-fighting genes may be able to work better. Before you can start treatment on this study, you will have screening tests. These tests will help the doctor decide if you are eligible to take part in this study. You will have blood drawn (about 3 teaspoons) to check your kidney and liver function (routine blood tests). You may have a bone marrow aspiration performed (if you have not had one in recent weeks). To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative urine pregnancy test. If you agree to take part in this study, you will receive azacytidine by subcutaneous (just under the skin) injection every day for 7 days. This course of treatment will be repeated every 3-8 weeks, depending on the results of your routine blood tests. Your doctor may increase or decrease your dose of azacytidine, depending on if you experience any side effects. You will continue to receive treatment on this study unless the disease gets worse or you experience any intolerable side effects. If the disease gets worse or you experience any intolerable side effects, you will be taken off this study. This is an investigational study. This is an investigational study. Azacytidine has been approved by the FDA for the treatment of myelodysplastic syndrome. Up to 37 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUG5-Azacytidine
Starting dose level: 75mg/m\^2 subcutaneously daily for seven days. Treatment cycles will be repeated every 3-8 weeks.
Sponsors
Celgene Corporation
M.D. Anderson Cancer Center
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
1. Patients with chronic lymphocytic leukemia (CLL), prolymphocytic leukemia, Richter's transformation or T-PLL who have previously been treated with fludarabine or another regime are eligible. 2. Patients with histologically or cytologically confirmed Richter's transformation. 3. Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic-pyruvic transaminase (SGPT) less than x 2 normal levels. 4. Women of childbearing potential who have a negative pregnancy test prior to azacytidine treatment. 5. Women of childbearing potential who agreed not to become pregnant and men agreed not to father a child while on azacytidine treatment. 6. Performance 0-2 (ECOG). Adequate liver function (bilirubin of less than2mg/dl) and renal function (creatinine less than 2mg/dl). Adequate cardiac functions (NYHA cardiac III-IV excluded). 7. Signed informed consent.
Exclusion criteria
1. Breast feeding or pregnant females. Patients of (male and female) childbearing potential should practice effective methods of contraception; otherwise, they will be excluded. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 2. Known or suspected hypersensitivity to azacytidine or Mannitol. 3. Active and uncontrolled infections. 4. Patients with advanced malignant hepatic tumors. 5. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tumor Response Rate (Complete, Partial) of Azacytidine | 3 to 8 weeks treatment cycles, continuation up to 1 year | Overall response rate includes percentage of participants with complete response (CR) plus partial response (PR) responses using the National Cancer Institute (NCI) International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for response: Complete response defined as no palpable lymph nodes, liver or spleen and absence of symptoms. Neutrophil count \> 15,00/Mic L, and platelet count more than 100,000/MicL. Hemoglobin should be \> 11g/dl without transfusions. Lymphocyte count \<4000/micL. On bone marrow aspirate lymphocyte % should be \<30%, and biopsy showing no lymphocyte infiltrate. A partial response was defined as more than or equal to 50% decrease in lymph nodes and liver and spleen size. Neutrophils \> 1500/ micL or \>50 % improvement from baseline, platelet count \>100,000/micL or \>50 % improvement from baseline. Hemoglobin \>11g/dl or \>50% improvement from baseline. A reduction of \>50% in Leukocyte count or \<30 % lymphocytes with residual disease on biopsy for nodular PR. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 09/21/2006 to 12/01/2010. All recruitment done at The University of Texas MD Anderson Cancer Center.
Pre-assignment details
The study was discontinued after 9 participants enrolled because of lack of efficacy and slow accrual.
Participants by arm
| Arm | Count |
|---|---|
| 5-Azacytidine 5-Azacytidine 75 mg/m\^2 subcutaneously daily for 7 days, cycle repeated every 3-8 weeks. | 9 |
| Total | 9 |
Baseline characteristics
| Characteristic | 5-Azacytidine |
|---|---|
| Age, Continuous | 74 years |
| Region of Enrollment United States | 9 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 9 / 9 |
| serious Total, serious adverse events | 0 / 9 |
Outcome results
Primary
Tumor Response Rate (Complete, Partial) of Azacytidine
Overall response rate includes percentage of participants with complete response (CR) plus partial response (PR) responses using the National Cancer Institute (NCI) International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for response: Complete response defined as no palpable lymph nodes, liver or spleen and absence of symptoms. Neutrophil count \> 15,00/Mic L, and platelet count more than 100,000/MicL. Hemoglobin should be \> 11g/dl without transfusions. Lymphocyte count \<4000/micL. On bone marrow aspirate lymphocyte % should be \<30%, and biopsy showing no lymphocyte infiltrate. A partial response was defined as more than or equal to 50% decrease in lymph nodes and liver and spleen size. Neutrophils \> 1500/ micL or \>50 % improvement from baseline, platelet count \>100,000/micL or \>50 % improvement from baseline. Hemoglobin \>11g/dl or \>50% improvement from baseline. A reduction of \>50% in Leukocyte count or \<30 % lymphocytes with residual disease on biopsy for nodular PR.
Time frame: 3 to 8 weeks treatment cycles, continuation up to 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5-Azacytidine | Tumor Response Rate (Complete, Partial) of Azacytidine | 0 percentage of participants |