Troxacitabine in Treating Patients With Chronic Myelogenous Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase II trial to study the effectiveness of troxacitabine in treating patients who have blast phase chronic myelogenous leukemia.

Detailed Description
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OBJECTIVES: I. Determine the response rate, in terms of achieving complete hematologic remission, partial hematologic remission, hematologic improvement, partial response, or back to chronic phase status, in patients with blastic phase chronic myelogenous leukemia treated with troxacitabine. II. Determine the proportion of patients whose disease returns to chronic phase and remains at that level for at least 3 months when treated with this drug. III. Determine the toxicity profile of this drug in these patients. IV. Determine the duration of survival of patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive troxacitabine IV over 30 minutes on days 1-5. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed every 4 weeks until relapse. PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study within 14 months.

Official Title
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A Phase II Study Of Troxatyl In Patients With CML Blastic Phase Disease

Conditions
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Leukemia

Intervention / Treatment
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* Drug: troxacitabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of Philadelphia chromosome-positive blastic phase chronic myelogenous leukemia (CML) with blasts of non-lymphoid origin Blastic phase defined as: At least 30% blasts in the blood or bone marrow OR Presence of extramedullary infiltration outside the liver or spleen No leukemic CNS involvement PATIENT CHARACTERISTICS: Age: 16 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL AST or ALT less than 3 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine less than 1.8 mg/dL if creatinine clearance at least 45 mL/min Other: No known hypersensitivity to troxacitabine or its analogues No active uncontrolled serious infection No other severe medical condition that would preclude study No neurologic or psychiatric disorders that would preclude informed consent No uncontrolled underlying medical condition or underlying condition that could be aggrevated by treatment Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: At least 24 hours since prior hydroxyurea Prior STI571 for blastic phase chronic myelogenous leukemia allowed No other prior chemotherapy for blastic phase disease Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: At least 14 days since prior investigational agents and recovered No other concurrent investigational agents

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: troxacitabine<br> | Drug: troxacitabine<br> <br> * Other names: 8 mg/m2 administered IV over 30 minutes per day for 5 consecutive days;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 4 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 8 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 12 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 16 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 20 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 24 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 28 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 32 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 36 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 40 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 44 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 48 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 52 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 56 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 60 | 
| Conventional Response Rate | Conventional Response Rate defined as the achievement of complete hematologic remission (CHR), partial hematologic remission (PHR), hematologic improvement (HI), partial response (PR), or back to chronic phase (BCP). | Week 64 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Returning to Chronic Phase |  | Throughout the study period of approximately 15 months. | 
| Toxicity Profile |  | Every 4 weeks throughout the study period of approximately 15 months. | 
| Survival Duration |  | Throughout the study period of approximately 15 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsing chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic myelogenous leukemia, BCR-ABL1 positive