Chronic Myelogenous LeukemiaPhase 3NCT00333840

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

A Phase 3 study testing imatinib mesilate, interferon-alpha (INF-a) and cytarabine (ARA-C) in people with Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 163 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Chronic Myelogenous Leukemia
What is being tested?: imatinib mesilate, interferon-alpha (INF-a) and cytarabine (ARA-C)
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 1,106 participants
Where: 163 sitesin 16 countries
Study dates: Jun 2000to Mar 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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
Additional protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

163 sites in 16 countries.

Country

City, postcode or hospital

163 sites in 16 countries

United States62 sites

Novartis Investigative Site
Albuquerque, New Mexico, 87109
Novartis Investigative Site
Albuquerque, New Mexico, 87131
Novartis Investigative Site
Ann Arbor, Michigan, 48109
Novartis Investigative Site
Atlanta, Georgia, 30342
Novartis Investigative Site
Baltimore, Maryland, 21201
Novartis Investigative Site
Beech Grove, Indiana, 46107
Novartis Investigative Site
Berkeley, California, 94704
Novartis Investigative Site
Billings, Montana, 59101
Novartis Investigative Site
Birmingham, Alabama, 35294
Novartis Investigative Site
Boston, Massachusetts, 02115
Novartis Investigative Site
Buffalo, New York, 14263
Novartis Investigative Site
Campbell, California, 95008
Novartis Investigative Site
Chapel Hill, North Carolina, 27599
Novartis Investigative Site
Charlotte, North Carolina, 28203
Novartis Investigative Site
Chicago, Illinois, 60611
Novartis Investigative Site
Chicago, Illinois, 60612
Novartis Investigative Site
Chicago, Illinois, 60637
Novartis Investigative Site
Cleveland, Ohio, 44195
Novartis Investigative Site
Columbus, Ohio, 43210
Novartis Investigative Site
Columbus, Ohio, 43215
Novartis Investigative Site
Dallas, Texas, 75235-9179
Novartis Investigative Site
Dallas, Texas, 75246
Novartis Investigative Site
Dayton, Ohio, 45429
Novartis Investigative Site
Decatur, Illinois, 62526
Novartis Investigative Site
Denver, Colorado, 80218
Novartis Investigative Site
Detroit, Michigan, 48202-2689
Novartis Investigative Site
Duarte, California, 91010
Novartis Investigative Site
Durham, North Carolina, 27710
Novartis Investigative Site
East Lansing, Michigan, 48910
Novartis Investigative Site
Farmington, New Mexico, 87131
Novartis Investigative Site
Hackensack, New Jersey, 07601
Novartis Investigative Site
Honolulu, Hawaii, 96813
Novartis Investigative Site
Houston, Texas, 77030
Novartis Investigative Site
La Jolla, California, 92093-0960
Novartis Investigative Site
Louisville, Kentucky, 40202
Novartis Investigative Site
Memphis, Tennessee, 38119
Novartis Investigative Site
Miami, Florida, 33176-2197
Novartis Investigative Site
Milwaukee, Wisconsin, 53215
Novartis Investigative Site
Minneapolis, Minnesota, 55455
Novartis Investigative Site
Montgomery, Alabama, 36106
Novartis Investigative Site
Nashville, Tennessee, 37203
Novartis Investigative Site
Nashville, Tennessee, 37205
Novartis Investigative Site
New Orleans, Louisiana, 70112
Novartis Investigative Site
New York, New York, 10017
Novartis Investigative Site
New York, New York, 10021
Novartis Investigative Site
New York, New York, 10029
Novartis Investigative Site
Omaha, Nebraska, 68198-7681
Novartis Investigative Site
Orlando, Florida, 32804
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15224
Novartis Investigative Site
Pittsburgh, Pennsylvania, 15232
Novartis Investigative Site
Portland, Oregon, 97239
Novartis Investigative Site
Providence, Rhode Island, 02903
Novartis Investigative Site
Salt Lake City, Utah, 84112
Novartis Investigative Site
Seattle, Washington, 98109-1024
Novartis Investigative Site
Spartanburg, South Carolina, 29303
Novartis Investigative Site
St Louis, Missouri, 63110
Novartis Investigative Site
Syracuse, New York, 13210
Novartis Investigative Site
Tucson, Arizona, 85724
Novartis Investigative Site
Tulsa, Oklahoma, 74136
Novartis Investigative Site
Winston-Salem, North Carolina, 27157
Novartis Investigative Site
Witchita, Kansas, 67214
Novartis Investigative Site
Worcester, Massachusetts, 01665

Other trials in United States

Germany16 sites

Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Dresden, 01307
Novartis Investigative Site
Düsseldorf, 40225
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Heidelberg, 69115
Novartis Investigative Site
Leipzig, 04103
Novartis Investigative Site
Mainz, 55101
Novartis Investigative Site
Mannheim, 68189
Novartis Investigative Site
Marburg, 35037
Novartis Investigative Site
München, 80804
Novartis Investigative Site
München, 81675
Novartis Investigative Site
Regensburg, 93042
Novartis Investigative Site
Rostock, 18057
Novartis Investigative Site
Stuttgart, 70376

Other trials in Germany

Australia11 sites

Novartis Investigative Site
Adelaide
Novartis Investigative Site
Brisbane
Novartis Investigative Site
Darlinghurst
Novartis Investigative Site
East Melbourne
Novartis Investigative Site
Nedlands
Novartis Investigative Site
Parkville
Novartis Investigative Site
Prahan
Novartis Investigative Site
South Brisbane
Novartis Investigative Site
St Leonards
Novartis Investigative Site
Sydney, 2050
Novartis Investigative Site
Westmead

Other trials in Australia

Canada11 sites

Novartis Investigative Site
Calgary, Alberta, T2N 4N2
Novartis Investigative Site
Edmonton, Alberta, T6G 1Z2
Novartis Investigative Site
Halifax, Nova Scotia, B3H 2Y9
Novartis Investigative Site
Hamilton, Ontario, L8N 3Z5
Novartis Investigative Site
London, Ontario, N6A 4G5
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Montreal, Quebec, H3A 1A1
Novartis Investigative Site
Ottawa, Ontario, K1H 8L6
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Novartis Investigative Site
Vancouver, British Columbia, V5Z 1M9
Novartis Investigative Site
Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Italy11 sites

Novartis Investigative Site
Bari, 70124
Novartis Investigative Site
Bologna, 40138
Novartis Investigative Site
Florence, 50134
Novartis Investigative Site
Genova, 16132
Novartis Investigative Site
Milan, 20162
Novartis Investigative Site
Naples, 80131
Novartis Investigative Site
Orbassano, 10043
Novartis Investigative Site
Pavia, 27100
Novartis Investigative Site
Pescara, 65124
Novartis Investigative Site
Pisa, 56126
Novartis Investigative Site
Reggio Calabria, 89123

Other trials in Italy

France10 sites

Novartis Investigative Site
Créteil, 94010
Novartis Investigative Site
Lille, 59037
Novartis Investigative Site
Lyon, 69437
Novartis Investigative Site
Marseille, 13273
Novartis Investigative Site
Nantes, 44035
Novartis Investigative Site
Paris, 75475
Novartis Investigative Site
Pessac, 33604
Novartis Investigative Site
Poitiers
Novartis Investigative Site
Strasbourg, 67098
Novartis Investigative Site
Vandœuvre-lès-Nancy, 54511

Other trials in France

United Kingdom10 sites

Novartis Investigative Site
Birmingham, B9 5SS
Novartis Investigative Site
Cambridge, CB2 2XY
Novartis Investigative Site
Cardiff, CF14 4XN
Novartis Investigative Site
Leeds, LS1 3EX
Novartis Investigative Site
Liverpool, L7 8XP
Novartis Investigative Site
London, EC1A 7BE
Novartis Investigative Site
London, SE5 9RS
Novartis Investigative Site
Manchester, M13 9WL
Novartis Investigative Site
Nottingham, NG5 1PB
Novartis Investigative Site
Plymouth

Other trials in United Kingdom

Spain8 sites

Novartis Investigative Site
Barcelona, 8025
Novartis Investigative Site
Barcelona, 8036
Novartis Investigative Site
Barcelona, 8907
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Madrid, 46010
Novartis Investigative Site
Salamanca, 37007
Novartis Investigative Site
Valencia, 46010

Other trials in Spain

Sweden8 sites

Novartis Investigative Site
Gothenburg, 143 45
Novartis Investigative Site
Linköping, 581 85
Novartis Investigative Site
Lund, 221 85
Novartis Investigative Site
Örebro, 70 185
Novartis Investigative Site
Stockholm, 141 86
Novartis Investigative Site
Stockholm, 171 76
Novartis Investigative Site
Umeå, 901 85
Novartis Investigative Site
Uppsala, 751 85

Other trials in Sweden

Belgium4 sites

Novartis Investigative Site
Brussels, 1000
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Godinne
Novartis Investigative Site
Leuven, 3000

Other trials in Belgium

Denmark3 sites

Novartis Investigative Site
Aarhus, 8000
Novartis Investigative Site
Copenhagen
Novartis Investigative Site
Herlev, 2730

Other trials in Denmark

Switzerland3 sites

Novartis Investigative Site
Basel, 4031
Novartis Investigative Site
Bern, 3010
Novartis Investigative Site
Sankt Gallen, 9007

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Netherlands2 sites

Novartis Investigative Site
Amsterdam, 1081HV
Novartis Investigative Site
Rotterdam

Other trials in Netherlands

Norway2 sites

Novartis Investigative Site
Oslo, 27
Novartis Investigative Site
Tromsø, 9038

Other trials in Norway

Austria1 site

Novartis Investigative Site
Vienna, 1090

Other trials in Austria

New Zealand1 site

Novartis Investigative Site
Auckland

Other trials in New Zealand

About this study

Official title: A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)

Conditions: Chronic Myelogenous Leukemia
Being tested: imatinib mesilate, interferon-alpha (INF-a), cytarabine (ARA-C)
Keywords: CML, STI571, imatinib, interferon, interferon alpha, cytosine arabinoside, chronic myeloid leukemia, Philadelphia chromosome positive
Medical subject headings: Leukemia, Myelogenous, Chronic, BCR-ABL Positive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

imatinib mesilateDrug
Also called Glivec®, Gleevec®, STI571
imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.
interferon-alpha (INF-a)Drug
Also called Roferon®-A, Intron®-A
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)Drug
cytarabine 20 mg/m^2/day (max 40 mg) SC for 10 days every month.

Study groups in NCT00333840
Study group	Role	What they receive
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. Receives: 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. Receives: Drug: imatinib mesilate; Drug: interferon-alpha (INF-a); Drug: cytarabine (ARA-C)

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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)
Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:
- progression to Accelerated Phase (AP) or Blast Crisis (BC)
- loss of Complete Hematological Response (CHR)
- loss of Major Cytogenetic Response (MCyR) confirmed
- loss of Major Cytogenetic Response (MCyR) unconfirmed
- increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)
- death (due to any cause when reported as primary reason for discontinuation of treatment).
Kaplan Meier estimates of the percentage of participants with Event Free Survival at the given 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.
Measured: 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)
Event-free survival is defined as the time between randomization and the earliest of any of the following events on treatment:
- progression to Accelerated Phase (AP) or Blast Crisis (BC)
- loss of Complete Hematological Response (CHR)
- loss of Major Cytogenic Response (MCyR) confirmed
- loss of Major Cytogenic Response (MCyR) unconfirmed
- increase in white blood cell count (WBC) if approved by the Study Management Committee (SMC)
- death (due to any cause when reported as primary reason for discontinuation of treatment).
The percentage of participants with Event Free Survival events in each category 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.
Measured: 144 months
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
Time to progression to AP/BC is defined as the time between randomization and either of the following events on treatment: death (due to CML when reported as primary reason for discontinuation of treatment) or progression to Accelerated Phase or Blast Crisis and is censored at last examination date for patients without event. No data after discontinuation of study treatment was included. The Kaplan Meier estimates of the percentage of participants with survival without progression to AP/BC at the given 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.
Measured: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Philadelphia chromosome positive (Ph+) metaphases) and amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.
Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % of Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.
Measured: 144 months
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
Bone marrow aspirate was performed to evaluate cytogenetic results (percentage of Ph chromosome (Ph+) containing metaphases) and the amount of blasts and promyelocytes in bone marrow to establish cytogenetic response.
Major Cytogenetic Response= Complete Response or Partial Response. Complete Cytogenetic Response= 0 % of Ph+ metaphases (out of 20 metaphases). Partial Cytogenetic Response= > 0 and ≤ 35 % Ph+ metaphases (out of 20 metaphases). The percentage of participants with cytogenetic response in each category was calculated.
Measured: 144 months
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant
Measured: 144 months
Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant
Measured: 144 months
Percentage of Participants With Major Molecular Response (First-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale.
Measured: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Percentage of Participants With Major Molecular Response (Second-line Treatment)
Major Molecular Response was determined using a quantitative polymerase chain reaction (PCR) laboratory test and was defined as BCR-ABL protein transcripts of ≤ 0.1% according to the international scale.
Measured: 12,24,36,48,60,72,84,96,108,120,132 and 144 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2000Mar 2012

First posted6 Jun 2006 (estimated)
Study startJun 2000
Primary completionMar 2012
Study completionMar 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Chronic Myelogenous LeukemiaStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 1,106 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00333840
Sponsor's protocol ID: CSTI571A 0106
Status last verified: Aug 2013
First submitted: 2 Jun 2006
Last updated: 14 Oct 2013
Results posted: Yes, on ClinicalTrials.gov

Publications

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.
PubMed 28273028
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.
PubMed 23620574
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.
PubMed 18256322

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 14 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase III Study of STI571 Versus Interferon-α (IFN-α) Combined With Cytarabine (Ara-C) in Patients With Newly Diagnosed Previously Untreated Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
ClinicalTrials.gov ID: NCT00333840
Acronym / sponsor ID: CSTI571A 0106
Conditions: Chronic Myelogenous Leukemia
Keywords: CML, STI571, imatinib, interferon, interferon alpha, cytosine arabinoside, chronic myeloid leukemia, Philadelphia chromosome positive
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,106 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Jun 2000
Primary completion: Mar 2012 (actual)
Study completion: Mar 2012 (actual)
First posted: 6 Jun 2006 (estimated)
Results: Posted 14 Oct 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
imatinib (STI571)	Experimental	Drug: imatinib mesilate, Drug: interferon-alpha (INF-a), Drug: cytarabine (ARA-C)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.
IFN-a+Ara-C	Active comparator	Drug: imatinib mesilate, Drug: interferon-alpha (INF-a), Drug: cytarabine (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.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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

Key exclusion criteria (5 listed)

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
Additional protocol-defined inclusion/exclusion criteria may apply

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
imatinib mesilateAlso: Glivec®, Gleevec®, STI571imatinib supplied as 100 mg and 400 mg tablets or 100 mg capsules.	Drug	IFN-a+Ara-C, imatinib (STI571)
interferon-alpha (INF-a)Also: Roferon®-A, Intron®-Ainterferon-alpha (IFN-a) subcutaneous (SC) injections escalated over 4 weeks to achieve a target dose of 5 MU/m^2/day.	Drug	IFN-a+Ara-C, imatinib (STI571)
cytarabine (ARA-C)cytarabine 20 mg/m^2/day (max 40 mg) SC for 10 days every month.	Drug	IFN-a+Ara-C, imatinib (STI571)

Primary outcome

Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)
Time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
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.

9 secondary outcomes

Kaplan Meier Estimates of Event Free Survival (All Randomized Participants)
Time frame: 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)
Time frame: 144 months
Kaplan Meier Estimates of Time to Progression to Accelerated Phase (AP) or Blast Crisis (BC) (All Randomized Participants)
Time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Percentage of Participants With Best Cytogenetic Response (First-line Treatment)
Time frame: 144 months
Percentage of Participants With Best Cytogenetic Response (Second-line Treatment)
Time frame: 144 months
Number of Participants With Serious Adverse Events as a Measure of Safety (First-line Treatment)
Time frame: 144 months
Number of Participants With Serious Adverse Events as a Measure of Safety (Second-line Treatment)
Time frame: 144 months
Percentage of Participants With Major Molecular Response (First-line Treatment)
Time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months
Percentage of Participants With Major Molecular Response (Second-line Treatment)
Time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months

Results and safety

Results posted to the registry on 14 Oct 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Imatinib (STI571)	553	267
IFN-a + Ara-C	553	7
Imatinib to IFN-a + Ara-C	0	0
IFN-a + Ara-C to Imatinib	0	0

Primary outcome: Kaplan-Meier Estimates of Overall Survival (All Randomized Participants)

Time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months. Number. Unit: Percentage of participants

Measure	Imatinib (STI571) n = 553	IFN-a + Ara-C n = 553
12 months (n = 553, 553)	98.9 (98 to 100)	97.7 (96 to 99)
24 months (n = 542, 512)	96.0	93.6
36 months (n = 518, 471)	92.4	89.8
48 months (n = 492, 441)	90.4	87.7
60 months (n = 475, 411)	89.4	85.4
72 months (n = 461, 388)	88.2	83.8
84 months (n = 446, 373)	86.6	83.1
96 months (n = 430, 358)	85.4	81.4

Population analysed: Intent-to-treat population included all randomized participants. n = number of participants at risk at the beginning of the specific time interval

9 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Imatinib (STI571)	226 of 551 (41%)	541 of 551 (98.2%)	Not reported
IFN-a + Ara-C	163 of 533 (30.6%)	531 of 533 (99.6%)	Not reported
Imatinib to IFN-a + Ara-C	2 of 14 (14.3%)	13 of 14 (92.9%)	Not reported
IFN-a + Ara-C to Imatinib	160 of 363 (44.1%)	347 of 363 (95.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28273028Hochhaus 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.
Derived from this study: PubMed 23620574Jain 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.
Derived from this study: PubMed 18256322Larson 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

163 sites in 16 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing imatinib mesilate, interferon-alpha (INF-a) and cytarabine (ARA-C) in people with Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 163 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 163 sites in United States, Germany, Australia, Canada, Italy and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Oct 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Kaplan-Meier Estimates of Overall Survival (All Randomized Participants) (time frame: 12,24,36,48,60,72,84,96,108,120,132 and 144 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00333840, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2013.