Clofarabine and Cyclophosphamide Combination in Acute Lymphoblastic Leukemia Patients
The goal of this clinical research study is to find the highest tolerable dose of the drugs clofarabine and cyclophosphamide that can be given together in the treatment of relapsed or refractory ALL. The safety of the combination treatment will also be studied.
- To establish toxicities and safety of the proposed combination
To establish the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination to proceed with the phase II part of the study
- To establish the efficacy (complete and overall response) of the proposed combination.
- To analyze pharmacokinetic (PK) and pharmacodynamic (PD) properties of clofarabine as well as the impact on DNA repair of leukemic blasts with the proposed combination.
Acute Lymphoblastic Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Study of Clofarabine Plus Cyclophosphamide for Relapsed and Refractory Acute Lymphoblastic Leukemia (ALL)|
- Maximum Tolerated Dose for Cyclophosphamide (MTD) [ Time Frame: First 14 days of each cycle ] [ Designated as safety issue: Yes ]MTD is dose at which there are no dose limiting toxicity (DLT) defined as any =/> grade 3 drug-related non-hematologic toxicity that occurs within the first 14 days after start of treatment. Evaluation using continual reassessment method; 3-5 Day Cycle
|Study Start Date:||March 2006|
|Study Completion Date:||April 2012|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: Clofarabine + Cyclophosphamide
Clofarabine 40 mg/m^2 daily for 3 Days + Cyclophosphamide starting 200 mg/m^2 every 12 hours for 3 days
40 mg/m^2 Daily for 3 Days
Other Names:Drug: Cyclophosphamide
Beginning dose 200 mg/m^2 every 12 hours for 3 days
Clofarabine is a drug that is designed to interfere and disrupt important metabolic pathways of cancer cells by interfering with their multiplication and slowing or stopping their growth. Cyclophosphamide is also designed to destroy cancer cells by interfering with their multiplication and slowing or stopping their growth and spread throughout the body. Cyclophosphamide is commonly used in the treatment of ALL.
If you are found to be eligible to take part in this study, you will receive clofarabine by vein over about 60 minutes, once a day for 3 to 5 days. Cyclophosphamide will be given by vein over about 3 hours, twice a day for 3 to 5 days. These 3-5 days are considered 1 cycle of therapy.
As the safety of this combination has not been established yet, at least the first 2 participants on this study will receive clofarabine for 3 days and cyclophosphamide at a lower dose than usually given for 3 days (6 doses). Should there be no serious side effects that can be related to the study drugs, the next group of 2 participants will receive clofarabine over 3 days and a slightly higher dose of cyclophosphamide for 3 days (6 doses). Should there still be no serious side effects at that level, 2 further levels will be tested where both clofarabine and cyclophosphamide are then given over 4 days and eventually 5 days. Should serious and study drug-related side effects occur at any point during this increase of doses, a certain dose level along this increase will be defined as the appropriate dose for all future participants to receive. It is estimated that about 30 participants will receive therapy during the dose escalations portion of this study (Phase I). It is estimated that about 25 more participants will receive therapy at the dose levels that are considered best (Phase II).
During treatment, you will have a physical exam at least once a week. You may also be asked about the level of your daily activities, how you are feeling, and which medications you are taking currently. Routine blood samples (about 1 tablespoon each) will be drawn at least 1-3 times weekly and more frequently if considered necessary. A bone marrow aspirate and/or biopsy will be repeated starting at about Day 14 and will be repeated every 1 to 2 weeks until the study doctors can decide for sure whether you have responded or not. In some cases, a repeat bone marrow test may not be necessary, but this decision will be made by your treating doctor.
If you respond well after your first round of therapy, you may receive up to 6 additional courses of therapy. Each course will be repeated about every 3 to 7 weeks at a slightly lower dose of both drugs than was used during the first round of therapy. Later doses can also be changed depending on what type of side effects you may experienced with earlier rounds of therapy.
At the end of the study, a heart scan (either an Echo or MUGA scan) will be repeated. About 1 tablespoon of blood will be taken for routine blood tests. A focused physical exam may also be repeated.
This is an investigational study. All drugs in this study are FDA approved and commercially available. Their use together in this study is investigational. . About 55 patients will take part in this study. All will be enrolled at M. D. Anderson.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00412243
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Stefan Faderl, MD||M.D. Anderson Cancer Center|