Clinical trial NCT00028847: Imatinib Mesylate and Cytarabine in Treating Patients With Newly Diagnosed Chronic Myeloid Leukemia
Official title: A Dose-ranging Phase I/II Study of STI571 in Combination With Cytarabin in Patients With First Chronic Phase Chronic Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: chronic phase chronic myelogenous leukemia
chronic myelogenous leukemia, BCR-ABL1 positive
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of dose-limiting toxicity and treatment-related toxicity per dose level
Secondary outcomes:
measure: Rate and duration of molecular response
measure: Rate and duration of complete hematological response
measure: Rate and duration of complete cytogenetic response
measure: Time to treatment failure
measure: Overall survival
Other outcomes:
Locations:
city: Brugge
country: Belgium
facility: AZ Sint-Jan
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Mont-Godinne Yvoir
country: Belgium
facility: Clinique Universitaire De Mont-Godinne
city: 's-Gravenhage
country: Netherlands
facility: HagaZiekenhuis - Locatie Leyenburg
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Vrije Universiteit Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Rotterdam
country: Netherlands
facility: Daniel Den Hoed Cancer Center at Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala Klinieken - locatie Sophia
Study officials:
affiliation: Daniel Den Hoed Cancer Center at Erasmus Medical Center
name: J.J. Cornelissen, MD
role: STUDY_CHAIR
References:
citation: 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, Lowenberg B, Valk PJ, Ossenkoppele GJ, Cornelissen JJ. Efficacy of escalated imatinib combined with cytarabine in newly diagnosed patients with chronic myeloid leukemia. Haematologica. 2010 Jun;95(6):914-21. doi: 10.3324/haematol.2009.016766. Epub 2009 Dec 16.
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, Lowenberg B, Ossenkoppele GJ, Cornelissen JJ. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia. Blood. 2008 Mar 1;111(5):2581-8. doi: 10.1182/blood-2007-08-107482. Epub 2008 Jan 2.
citation: Thielen N, van der Holt B, Cornelissen JJ, Verhoef GE, Gussinklo T, Biemond BJ, Daenen SM, Deenik W, van Marwijk Kooy R, Petersen E, Smit WM, Valk PJ, Ossenkoppele GJ, Janssen JJ. Imatinib discontinuation in chronic phase myeloid leukaemia patients in sustained complete molecular response: a randomised trial of the Dutch-Belgian Cooperative Trial for Haemato-Oncology (HOVON). Eur J Cancer. 2013 Oct;49(15):3242-6. doi: 10.1016/j.ejca.2013.06.018. Epub 2013 Jul 19.