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

NCT00333840 | Completed Phase 3 Results

• 1 other identifier: CSTI571A 0106
• Study Type: interventional
• Target: 1,106
• Locations: 15 countries
• Sites: 162

Brief Summary

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.

Conditions

Chronic Myelogenous Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)

  Overall survival was defined as the time between date of randomization and death due to any cause. The time was censored at last examination date for patients who were still being treated and at date of last contact for patients who discontinued treatment. Kaplan-Meier estimates of the percentage of participants at each time point was calculated. This outcome was measured in all randomized patients, regardless of whether crossover occurred, i.e., events that occurred in patients, who had crossed over, were attributed following crossover to the original randomized treatment.

  12,24,36,48,60,72,84,96,108,120,132 and 144 months

Secondary Outcomes (9)

• Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)

  12,24,36,48,60,72,84,96,108,120,132 and 144 months

• Percentage of Participants With Event Free Survival Events (All Randomized Participants)

  144 months

• Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)

  12,24,36,48,60,72,84,96,108,120,132 and 144 months

• Percentage of Participants With Best Cytogenetic Response (First-line Treatment)

  144 months

• Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)

  144 months

Study Arms (2)

imatinib (STI571)

EXPERIMENTAL

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.

Drug: imatinib mesilate; Drug: interferon-alpha (INF-a); Drug: cytarabine (ARA-C)

IFN-a+Ara-C

ACTIVE COMPARATOR

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.

Drug: imatinib mesilate; Drug: interferon-alpha (INF-a); Drug: cytarabine (ARA-C)

Interventions

imatinib mesilate DRUG

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

Also known as: Glivec®, Gleevec®, STI571

IFN-a+Ara-C; imatinib (STI571)

interferon-alpha (INF-a) DRUG

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

Also known as: Roferon®-A, Intron®-A

IFN-a+Ara-C; imatinib (STI571)

cytarabine (ARA-C) DRUG

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

IFN-a+Ara-C; imatinib (STI571)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (163)

Novartis Investigative Site

Birmingham, Alabama, 35294, United States

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Montgomery, Alabama, 36106, United States

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Tucson, Arizona, 85724, United States

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Berkeley, California, 94704, United States

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Campbell, California, 95008, United States

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Duarte, California, 91010, United States

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La Jolla, California, 92093-0960, United States

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Denver, Colorado, 80218, United States

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Miami, Florida, 33176-2197, United States

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Orlando, Florida, 32804, United States

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Atlanta, Georgia, 30342, United States

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Honolulu, Hawaii, 96813, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Chicago, Illinois, 60637, United States

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Decatur, Illinois, 62526, United States

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Beech Grove, Indiana, 46107, United States

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Witchita, Kansas, 67214, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, 70112, United States

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Baltimore, Maryland, 21201, United States

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Boston, Massachusetts, 02115, United States

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Worcester, Massachusetts, 01665, United States

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Ann Arbor, Michigan, 48109, United States

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Detroit, Michigan, 48202-2689, United States

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East Lansing, Michigan, 48910, United States

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Minneapolis, Minnesota, 55455, United States

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St Louis, Missouri, 63110, United States

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Billings, Montana, 59101, United States

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Omaha, Nebraska, 68198-7681, United States

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Hackensack, New Jersey, 07601, United States

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Albuquerque, New Mexico, 87109, United States

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Albuquerque, New Mexico, 87131, United States

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Farmington, New Mexico, 87131, United States

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Buffalo, New York, 14263, United States

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New York, New York, 10017, United States

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New York, New York, 10021, United States

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New York, New York, 10029, United States

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Syracuse, New York, 13210, United States

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Chapel Hill, North Carolina, 27599, United States

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Charlotte, North Carolina, 28203, United States

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Durham, North Carolina, 27710, United States

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Winston-Salem, North Carolina, 27157, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43210, United States

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Columbus, Ohio, 43215, United States

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Dayton, Ohio, 45429, United States

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Tulsa, Oklahoma, 74136, United States

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Portland, Oregon, 97239, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Pittsburgh, Pennsylvania, 15232, United States

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Providence, Rhode Island, 02903, United States

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Spartanburg, South Carolina, 29303, United States

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Memphis, Tennessee, 38119, United States

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Nashville, Tennessee, 37203, United States

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Nashville, Tennessee, 37205, United States

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Dallas, Texas, 75235-9179, United States

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Dallas, Texas, 75246, United States

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Houston, Texas, 77030, United States

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Salt Lake City, Utah, 84112, United States

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Seattle, Washington, 98109-1024, United States

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Milwaukee, Wisconsin, 53215, United States

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Adelaide, Australia

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Brisbane, Australia

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Darlinghurst, Australia

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East Melbourne, Australia

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Nedlands, Australia

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Parkville, Australia

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Prahan, Australia

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South Brisbane, Australia

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St Leonards, Australia

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Sydney, 2050, Australia

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Westmead, Australia

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Vienna, 1090, Austria

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Brussels, 1000, Belgium

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Brussels, 1200, Belgium

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Godinne, Belgium

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Leuven, 3000, Belgium

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Calgary, Alberta, T2N 4N2, Canada

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Edmonton, Alberta, T6G 1Z2, Canada

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Vancouver, British Columbia, V5Z 1M9, Canada

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Winnipeg, Manitoba, R3E 0V9, Canada

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Halifax, Nova Scotia, B3H 2Y9, Canada

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Hamilton, Ontario, L8N 3Z5, Canada

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London, Ontario, N6A 4G5, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H1T 2M4, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Aarhus, 8000, Denmark

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Copenhagen, Denmark

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Herlev, 2730, Denmark

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Créteil, 94010, France

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Lille, 59037, France

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Lyon, 69437, France

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Marseille, 13273, France

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Nantes, 44035, France

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Paris, 75475, France

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Pessac, 33604, France

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Poitiers, France

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Strasbourg, 67098, France

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Vandœuvre-lès-Nancy, 54511, France

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Berlin, 13353, Germany

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Dresden, 01307, Germany

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Düsseldorf, 40225, Germany

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Frankfurt, 60590, Germany

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Freiburg im Breisgau, 79106, Germany

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Hamburg, 20246, Germany

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Heidelberg, 69115, Germany

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Leipzig, 04103, Germany

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Mainz, 55101, Germany

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Mannheim, 68189, Germany

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Marburg, 35037, Germany

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München, 80804, Germany

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München, 81675, Germany

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Regensburg, 93042, Germany

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Rostock, 18057, Germany

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Stuttgart, 70376, Germany

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Bari, 70124, Italy

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Genova, 16132, Italy

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Milan, 20162, Italy

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Napoli, 80131, Italy

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Orbassano, 10043, Italy

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Pavia, 27100, Italy

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Pescara, 65124, Italy

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Pisa, 56126, Italy

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Reggio Calabria, 89123, Italy

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Amsterdam, 1081HV, Netherlands

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Rotterdam, Netherlands

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Auckland, New Zealand

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Oslo, 27, Norway

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Tromsø, 9038, Norway

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Barcelona, 8025, Spain

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Barcelona, 8036, Spain

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Barcelona, 8907, Spain

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Madrid, 28034, Spain

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Madrid, 28222, Spain

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Madrid, 46010, Spain

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Salamanca, 37007, Spain

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Valencia, 46010, Spain

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Gothenburg, 143 45, Sweden

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Linköping, 581 85, Sweden

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Lund, 221 85, Sweden

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Örebro, 70 185, Sweden

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Stockholm, 141 86, Sweden

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Stockholm, 171 76, Sweden

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Umeå, 901 85, Sweden

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Uppsala, 751 85, Sweden

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Basel, 4031, Switzerland

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Bern, 3010, Switzerland

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Sankt Gallen, 9007, Switzerland

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Birmingham, B9 5SS, United Kingdom

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Cambridge, CB2 2XY, United Kingdom

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Cardiff, CF14 4XN, United Kingdom

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Leeds, LS1 3EX, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, SE5 9RS, United Kingdom

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Manchester, M13 9WL, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Plymouth, United Kingdom

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Related Publications (3)

• 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.

  PMID: 28273028 DERIVED

• 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.

  PMID: 23620574 DERIVED

• 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.

  PMID: 18256322 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; Interferon-alpha; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Cytidine; Pyrimidine Nucleosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2006
• First Posted: June 6, 2006
• Study Start: June 1, 2000
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 14, 2013
• Results First Posted: October 14, 2013

Record last verified: 2013-08

Locations

BE (4); CH (3); SE (8); NO (2); AU (11); DE (16); IT (11); US (62); NZ (1); GB (10); FR (10); CA (11); NL (2); ES (8); DK (3)