Clofarabine and Cyclophosphamide Combination in Acute Lymphoblastic Leukemia Patients

March 8, 2013 updated by: M.D. Anderson Cancer Center

Phase I/II Study of Clofarabine Plus Cyclophosphamide for Relapsed and Refractory Acute Lymphoblastic Leukemia (ALL)

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.

Objectives:

Phase I:

  1. To establish toxicities and safety of the proposed combination

  2. 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

    Phase II:

  3. To establish the efficacy (complete and overall response) of the proposed combination.
  4. 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Previously treated ALL (including Burkitt's lymphoma and lymphoblastic lymphoma) in relapse or primary refractory. For patients in first relapse, the first remission duration may not exceed 12 months.
  2. Age >/= 21 years.
  3. Zubrod performance status </= 3.
  4. Adequate liver function (bilirubin </= 2.5 mg/dL and Serum glutamic pyruvic transaminase (SGPT or SGOT) </= 3 * ULN, unless considered due to tumor), and renal function (glomerular filtration rate [GFR] >/= 60 mL/min). Even if organ function abnormalities are considered due to tumor, the upper limit for bilirubin is </= 5 mg/dL and creatinine </= 3 mg/dL.
  5. Male and female patients who are fertile agree to use an effective barrier method of birth control (e.g., latex condom, diaphragm, cervical cap, etc.) to avoid pregnancy. Female patients need a negative serum or urine pregnancy test within 14 days of study enrollment (applies only if patient is of childbearing potential. Non-childbearing is defined as >/= 1 year postmenopausal or surgically sterilized).

Exclusion Criteria:

  1. Patients with active heart disease (New York Heart Association (NYHA) class >/= 3 as assessed by history and physical examination).
  2. Patients with a cardiac ejection fraction (as measured by either Multi Gated Acquisition Scan (MUGA) or echocardiogram) < 45% are excluded.
  3. Patients who receive other chemotherapy. Patients must have been off previous therapy for >/= 2 weeks and must have recovered from acute toxicity of all previous therapy prior to enrollment. (Concurrent therapy for central nervous system (CNS) prophylaxis or treatment for CNS relapse is permitted). Treatment may start earlier if necessitated by the patient's medical condition following discussion with the Principal Investigator.
  4. Pregnant and breast-feeding patients are excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Clofarabine + Cyclophosphamide
Clofarabine 40 mg/m^2 daily for 3 Days + Cyclophosphamide starting 200 mg/m^2 every 12 hours for 3 days
Drug: Clofarabine
40 mg/m^2 Daily for 3 Days
Other Names:
  • Clolar
  • Clorarex
Drug: Cyclophosphamide
Beginning dose 200 mg/m^2 every 12 hours for 3 days
Other Names:
  • Cytoxan
  • Neosar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose for Cyclophosphamide (MTD)
Time Frame: First 14 days of each cycle
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
First 14 days of each cycle

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

Genzyme, a Sanofi Company

Investigators

  • Principal Investigator: Stefan Faderl, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

April 1, 2012

Study Completion (Actual)

April 1, 2012

Study Registration Dates

First Submitted

December 14, 2006

First Submitted That Met QC Criteria

December 15, 2006

First Posted (Estimate)

December 18, 2006

Study Record Updates

Last Update Posted (Estimate)

March 12, 2013

Last Update Submitted That Met QC Criteria

March 8, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-0552

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Lymphoblastic Leukemia

Clinical Trials on Clofarabine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Norway

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe