Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia

Leukemia Clinical Trial

Official title:

A Dose-ranging Phase I/II Study of STI571 in Combination With Cytarabin in Patients With First Chronic Phase Chronic Myeloid Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00028847
• Other study ID #: CDR0000069141
• Secondary ID: CKTO-2001-03HOVO
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: January 4, 2002
• Last updated: September 16, 2013
• Start date: April 2001

Study information

• Verified date: August 2011
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining imatinib mesylate and chemotherapy may kill more cancer cells.

PURPOSE: Phase I/II trial to study the effectiveness of imatinib mesylate plus cytarabine in treating patients who have newly diagnosed chronic myeloid leukemia.

Description:

OBJECTIVES:

• Determine the maximum tolerated dose of imatinib mesylate and cytarabine in patients with newly diagnosed chronic phase chronic myeloid leukemia.

• Determine the feasibility of this regimen as defined by dose-limiting toxicity of this regimen and treatment-related mortality in no more than 5% of these patients.

• Determine the rate and duration of molecular response, complete hematological response, and complete cytogenetic response in patients treated with this regimen.

• Determine the time to treatment failure of patients treated with this regimen.

• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of imatinib mesylate and cytarabine.

Patients receive oral imatinib mesylate alone once daily on days 1-21. Patients then receive oral imatinib mesylate once daily and cytarabine IV over 1-3 hours on days 1-7. Combination therapy repeats every 28-42 days for 2 courses. Patients then receive maintenance oral imatinib mesylate once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 5-20 patients receive escalating doses of imatinib mesylate and cytarabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 5/5, 5/10, or 5/20 patients experience dose-limiting toxicity.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 30-60 patients will be accrued for this study within 2 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS:

• Newly diagnosed chronic myeloid leukemia in first chronic phase (within the past 6 months)

• Philadelphia-chromosome positive OR

• bcr-abl rearrangement

• No prior treatment within the past 6 months other than hydroxyurea

PATIENT CHARACTERISTICS:

Age:

• 18 to 65

Performance status:

• WHO 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• No hepatic dysfunction

• Bilirubin less than 2 times normal

• ALT less than 4 times normal

Renal:

• No renal dysfunction

• Creatinine less than 2.3 mg/dL

Cardiovascular:

• No severe cardiac dysfunction

• No New York Heart Association class II-IV heart disease

Pulmonary:

• No severe pulmonary disease

Other:

• HIV negative

• No severe neurologic disease

• No active uncontrolled infection

• No other active malignancy within the past 5 years except basal cell skin cancer or stage 0 cervical cancer

• Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics

• No concurrent allogeneic transplantation with an HLA-A, B, DR-matched sibling donor or matched-unrelated donor

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• See Disease Characteristics

Radiotherapy:

• See Disease Characteristics

Surgery:

• See Disease Characteristics

Other:

• No concurrent grapefruit or grapefruit juice

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase

Intervention

Drug:
• cytarabine

• imatinib mesylate

Locations

Country	Name	City	State
Belgium	AZ Sint-Jan	Brugge
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Clinique Universitaire De Mont-Godinne	Mont-Godinne Yvoir
Netherlands	HagaZiekenhuis - Locatie Leyenburg	's-Gravenhage
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	Daniel Den Hoed Cancer Center at Erasmus Medical Center	Rotterdam
Netherlands	University Medical Center Utrecht	Utrecht
Netherlands	Isala Klinieken - locatie Sophia	Zwolle

Sponsors (1)

Lead Sponsor	Collaborator
Commissie Voor Klinisch Toegepast Onderzoek

Countries where clinical trial is conducted

Belgium,  Netherlands, 

References & Publications (2)

Deenik W, Janssen JJ, van der Holt B, Verhoef GE, Smit WM, Kersten MJ, Daenen SM, Verdonck LF, Ferrant A, Schattenberg AV, Sonneveld P, van Marwijk Kooy M, Wittebol S, Willemze R, Wijermans PW, Beverloo HB, Löwenberg B, Valk PJ, Ossenkoppele GJ, Corneliss — View Citation

Deenik W, van der Holt B, Verhoef GE, Smit WM, Kersten MJ, Kluin-Nelemans HC, Verdonck LF, Ferrant A, Schattenberg AV, Janssen JJ, Sonneveld P, van Marwijk Kooy M, Wittebol S, Willemze R, Wijermans PW, Westveer PH, Beverloo HB, Valk P, Löwenberg B, Ossenk — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicity and treatment-related toxicity per dose level			Yes
Secondary	Rate and duration of molecular response			No
Secondary	Rate and duration of complete hematological response			No
Secondary	Rate and duration of complete cytogenetic response			No
Secondary	Time to treatment failure			No
Secondary	Overall survival			No