Troxacitabine in Treating Patients With Chronic Myelogenous Leukemia

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: troxacitabine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa General Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
      • Maisonneuve-Rosemont Hospital
    • Montreal, Quebec, Canada, H3A 1A1
      • Royal Victoria Hospital - Montreal
• United States
  • California
    • Duarte, California, United States, 91010-3000
      • Cancer Center and Beckman Research Institute, City of Hope
    • Los Angeles, California, United States, 90033-0804
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Comprehensive Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • MD Anderson Cancer Center Orlando
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Johns Hopkins Oncology Center
  • New York
    • Albany, New York, United States, 12208
      • Cancer Center of Albany Medical Center
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4283
      • University of Pennsylvania Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center of Thomas Jefferson University - Philadelphia
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 120 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: troxacitabine	Drug: troxacitabine; Other Names: 8 mg/m2 administered IV over 30 minutes per day for 5 consecutive days

What is the study measuring?

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	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.

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2000
• Primary Completion (Actual): March 27, 2002
• Study Completion (Actual): March 27, 2002

Study Registration Dates

• First Submitted: March 3, 2001
• First Submitted That Met QC Criteria: February 25, 2004
• First Posted (Estimate): February 26, 2004

Study Record Updates

• Last Update Posted (Actual): June 10, 2021
• Last Update Submitted That Met QC Criteria: June 7, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: blastic phase chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic myelogenous leukemia, BCR-ABL1 positive
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Troxacitabine
• Other Study ID Numbers: BCH-4556-214; CDR0000068498 (Registry Identifier: PDQ (Physician Data Query)); NCI-V01-1648