Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia

NCT ID: NCT00333840

Last Updated: 2013-10-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1106 participants

Study Classification

INTERVENTIONAL

Study Start Date

2000-06-30

Study Completion Date

2012-03-31

Brief Summary

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The purpose of this study is to evaluate and compare the side effects and anti-leukemic benefits of imatinib with those of interferon and Ara-C for patients who have chronic myeloid leukemia (CML) in the chronic phase. Patients in this study will be randomized (1:1) to receive either interferon plus Ara-C or imatinib as initial treatment.

Detailed Description

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Conditions

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Chronic Myelogenous Leukemia

Keywords

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CML STI571 imatinib interferon interferon alpha cytosine arabinoside chronic myeloid leukemia Philadelphia chromosome positive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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imatinib (STI571)

In the first-line treatment period participants received imatinib 400 mg orally once daily in the morning. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to receive interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injection for 10 days every month. Maximum study duration was 11.5 years.

Group Type EXPERIMENTAL

imatinib mesilate

Intervention Type DRUG

imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.

interferon-alpha (INF-a)

Intervention Type DRUG

interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day.

cytarabine (ARA-C)

Intervention Type DRUG

cytarabine 20 mg/m\^2/day (max 40 mg) SC for 10 days every month.

IFN-a+Ara-C

In the first-line treatment period participants received interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day. After the maximum tolerated dose of IFN-a was achieved, participants also received cytarabine (ARA-C) 20 mg/m\^2/day (max 40 mg) SC injections for 10 days every month. Hydroxyurea was permitted in the first 6 months to keep the white blood cell count (WBC) below 20.0 X 10\^9/liter. If protocol specific criteria applied, participants were eligible to crossover to the second-line treatment period to receive imatinib (STI571). IFN treatment was discontinued with protocol amendment 6. Maximum study duration was 8 years.

Group Type ACTIVE_COMPARATOR

imatinib mesilate

Intervention Type DRUG

imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.

interferon-alpha (INF-a)

Intervention Type DRUG

interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day.

cytarabine (ARA-C)

Intervention Type DRUG

cytarabine 20 mg/m\^2/day (max 40 mg) SC for 10 days every month.

Interventions

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imatinib mesilate

imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.

Intervention Type DRUG

interferon-alpha (INF-a)

interferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m\^2/day.

Intervention Type DRUG

cytarabine (ARA-C)

cytarabine 20 mg/m\^2/day (max 40 mg) SC for 10 days every month.

Intervention Type DRUG

Other Intervention Names

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Glivec® Gleevec® STI571 Roferon®-A Intron®-A

Eligibility Criteria

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Inclusion Criteria

* Must have signed consent for Amendment 5
* Must have completed visit 62 of the core IRIS trial or be in follow-up
* Must be on STI571 treatment
* If on IFN treatment, must be willing to cross over to STI571 treatment

Exclusion Criteria

* Patients who have discontinued from the study and are in follow-up
* Patients who are on IFN treatment and do not want to cross over to STI571 treatment
* Patients who have not consented to amendment 5
* Patients who did not complete the amendment 5 protocol
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Birmingham, Alabama, United States

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Montgomery, Alabama, United States

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Tucson, Arizona, United States

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Countries

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United States Australia Austria Belgium Canada Denmark France Germany Italy Netherlands New Zealand Norway Spain Sweden Switzerland United Kingdom

References

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Hochhaus A, Larson RA, Guilhot F, Radich JP, Branford S, Hughes TP, Baccarani M, Deininger MW, Cervantes F, Fujihara S, Ortmann CE, Menssen HD, Kantarjian H, O'Brien SG, Druker BJ; IRIS Investigators. Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. N Engl J Med. 2017 Mar 9;376(10):917-927. doi: 10.1056/NEJMoa1609324.

Reference Type DERIVED
PMID: 28273028 (View on PubMed)

Jain P, Kantarjian H, Nazha A, O'Brien S, Jabbour E, Romo CG, Pierce S, Cardenas-Turanzas M, Verstovsek S, Borthakur G, Ravandi F, Quintas-Cardama A, Cortes J. Early responses predict better outcomes in patients with newly diagnosed chronic myeloid leukemia: results with four tyrosine kinase inhibitor modalities. Blood. 2013 Jun 13;121(24):4867-74. doi: 10.1182/blood-2013-03-490128. Epub 2013 Apr 25.

Reference Type DERIVED
PMID: 23620574 (View on PubMed)

Larson RA, Druker BJ, Guilhot F, O'Brien SG, Riviere GJ, Krahnke T, Gathmann I, Wang Y; IRIS (International Randomized Interferon vs STI571) Study Group. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008 Apr 15;111(8):4022-8. doi: 10.1182/blood-2007-10-116475. Epub 2008 Feb 6.

Reference Type DERIVED
PMID: 18256322 (View on PubMed)

Other Identifiers

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CSTI571A 0106

Identifier Type: -

Identifier Source: org_study_id