5-Azacytidine (Azacytidine; Vidaza) in Chronic Lymphocytic Leukemia

Leukemia Clinical Trial

Official title:

Phase II Study of 5-Azacytidine (Azacytidine; Vidaza) in Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00413478
• Other study ID #: 2006-0428
• Secondary ID: NCI-2010-00552
• Status: Terminated
• Phase: Phase 2
• First received: December 15, 2006
• Last updated: June 26, 2015
• Start date: September 2006
• Est. completion date: November 2014

Study information

• Verified date: June 2015
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: November 2014
• Est. primary completion date: November 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

Drug:
• 5-Azacytidine
Starting dose level: 75mg/m^2 subcutaneously daily for seven days. Treatment cycles will be repeated every 3-8 weeks.

Locations

Country	Name	City	State
United States	University of Texas MD Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	Celgene Corporation

Country where clinical trial is conducted

United States, 

References & Publications (1)

Malik A, Shoukier M, Garcia-Manero G, Wierda W, Cortes J, Bickel S, Keating MJ, Estrov Z. Azacitidine in fludarabine-refractory chronic lymphocytic leukemia: a phase II study. Clin Lymphoma Myeloma Leuk. 2013 Jun;13(3):292-5. doi: 10.1016/j.clml.2012.11.0 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	3 to 8 weeks treatment cycles, continuation up to 1 year	No

External Links

•   University of Texas MD Anderson Cancer Center Website