Chronic Myeloid LeukemiaPhase 3SPIRITNCT00219739
STI571 ProspectIve RandomIzed Trial: SPIRIT
A Phase 3 study testing Imatinib mesylate 400 mg, Imatinib mesylate 600 mg and Imatinib 400 mg + Peg-Interferon in people with Chronic Myeloid Leukemia, run by Poitiers University Hospital at 1 site in France.
Trial summary
To test whether increasing the dose of imatinib or combining it with IFNalpha or ara-C increases the rate of molecular response (as measured by the decrease in BCR-ABL transcripts after 12 months of treatment) in patients with previously untreated CML in chronic phase. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Imatinib mesylate 400 mg, Imatinib mesylate 600 mg and Imatinib 400 mg + Peg-Interferon
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 789 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2003to Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients over 18 years of age
- Patients with Bcr-Abl positive CML in chronic phase.
- Patients within 14 weeks of diagnosis and previously untreated for CML except for hydroxyurea and/or anagrelide.
- No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- ECOG performance score of 0-2
- acceptable hepatic, renal, and cardiac function
- Informed consent signed up
Who cannot join
- Depressive syndrome not controlled
- Uncontrolled medical illnesses.
- Women with childbearing potential and male patients who are unwilling or unable to use an adequate method to avoid pregancy for the entire period of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic Myelogenous Leukemia (CML) in Chronic Phase
To test whether increasing the dose of imatinib or combining it with IFNalpha or ara-C increases the rate of molecular response (as measured by the decrease in BCR-ABL transcripts after 12 months of treatment) in patients with previously untreated CML in chronic phase.
To compare overall survival in a selected arm according to molecular response at 1 year from randomization with the reference arm.
Read the detailed description
Imatinib at 400 mg daily has emerged as the preferred therapy for newly diagnosed CML patients who do not undergo allogeneic stem cell transplant.
A phase III randomized study, comparing imatinib at 400 mg per day to interferon plus cytarabine in newly diagnosed chronic phase CML patients enrolled 1106 patients from June 2000 to January 2001. 553 patients were randomized to each treatment. For comparative purposes, at 6 months, 75% of patients randomized to imatinib obtained a major cytogenetic response with 51% complete responses. Despite these impressive results, only a minority of patients treated with imatinib in this study achieved a molecular remission. When analyzed by log reduction in Bcr-Abl transcript levels using quantitative RT-PCR, 39% of patients achieved a 3-log reduction in Bcr-Abl levels, but only 13% and 3% achieved a 4- and 5-log reduction, respectively.2 To improve upon these results, various groups have tried higher doses of imatinib, and combinations of imatinib with interferon alpha or cytarabine. Each of these studies has used cytogenetic responses as the major endpoint.
Each of these therapies has increased toxicity as compared to 400 mg of imatinib alone and the rates of molecular remissions have not been reported.
Thus the purpose of this study is to first determine whether higher doses of imatinib or combining Imatinib with interferon or Ara-C would result in higher rates of molecular responses and if so, in better survival.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Imatinib mesylate 400 mg, Imatinib mesylate 600 mg, Imatinib 400 mg + Peg-Interferon, Imatinib mesylate 400 mg + Cytarabine
- Keywords
- CML, Imatinib, Interferon, Cytarabine
- 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 mesylate 400 mgDrug
Imatinib mesylate 600 mgDrug
Imatinib 400 mg + Peg-InterferonDrug
Imatinib mesylate 400 mg + CytarabineDrug
| Study group | Role | What they receive |
|---|---|---|
| Imatinib mesylate 400 mg | Experimental | Not described Receives: Drug: Imatinib mesylate 400 mg; Drug: Imatinib mesylate 600 mg; Drug: Imatinib 400 mg + Peg-Interferon; Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 600 mg | Experimental | Not described Receives: Drug: Imatinib mesylate 400 mg; Drug: Imatinib mesylate 600 mg; Drug: Imatinib 400 mg + Peg-Interferon; Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 400 mg +Peg interferon | Experimental | Not described Receives: Drug: Imatinib mesylate 400 mg; Drug: Imatinib mesylate 600 mg; Drug: Imatinib 400 mg + Peg-Interferon; Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 400 mg +Cytarabine | Experimental | Not described Receives: Drug: Imatinib mesylate 400 mg; Drug: Imatinib mesylate 600 mg; Drug: Imatinib 400 mg + Peg-Interferon; Drug: Imatinib mesylate 400 mg + Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival improvement
Secondary outcomes (5)
Molecular response improvement at 1 year
Measured: 1 year
Hematological, cytogenetic responses improvement
Measured: 1 year
Duration of responses improvement
Survival without progression improvement
Acceptable toxicity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startSep 2003
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Poitiers University HospitalThe 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 789 participants (actual)
Sponsor and investigators
- Lead sponsor
- Poitiers University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France, Novartis, Roche Pharma AG
- Responsible party
- Sponsor
- Investigators
- François GUILHOT, MD, Study chair, Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00219739
- Sponsor's protocol ID
- SPIRIT
- Acronym
- SPIRIT
- Status last verified
- Jun 2016
- First submitted
- 13 Sep 2005
- Last updated
- 13 Apr 2020
- Results posted
- No
Publications
Bruzzoni-Giovanelli H, Gonzalez JR, Sigaux F, Villoutreix BO, Cayuela JM, Guilhot J, Preudhomme C, Guilhot F, Poyet JL, Rousselot P. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget. 2015 Nov 3;6(34):36269-77. doi: 10.18632/oncotarget.5915.
PubMed 26474455Delord M, Rousselot P, Cayuela JM, Sigaux F, Guilhot J, Preudhomme C, Guilhot F, Loiseau P, Raffoux E, Geromin D, Genin E, Calvo F, Bruzzoni-Giovanelli H. High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients. Oncotarget. 2013 Oct;4(10):1582-91. doi: 10.18632/oncotarget.1050.
PubMed 24123600Johnson-Ansah H, Guilhot J, Rousselot P, Rea D, Legros L, Rigal-Huguet F, Nicolini FE, Mahon FX, Preudhomme C, Guilhot F. Tolerability and efficacy of pegylated interferon-alpha-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. Cancer. 2013 Dec 15;119(24):4284-9. doi: 10.1002/cncr.28328. Epub 2013 Sep 16.
PubMed 24105694Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, Guilhot F; SPIRIT Investigators; France Intergroupe des Leucemies Myeloides Chroniques (Fi-LMC). Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010 Dec 23;363(26):2511-21. doi: 10.1056/NEJMoa1004095.
PubMed 21175313
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Prospective Randomized Comparison of Imatinib at a Dose of 400mg in Combination With Peg-Interferon-alpha2a (Peg-IFNa2a) or Cytarabine (Ara-C)Versus Imatinib at a Dose of 600mg Versus Imatinib a Dose of 400mg for Previously Untreated Chronic Myelogenous Leukemia (CML) in Chronic Phase
- ClinicalTrials.gov ID
- NCT00219739
- Acronym / sponsor ID
- SPIRIT / SPIRIT
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- CML, Imatinib, Interferon, Cytarabine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 789 participants (actual)
- Lead sponsor
- Poitiers University HospitalUniversity, hospital or other
- Collaborators
- Ministry of Health, France, Novartis, Roche Pharma AG
- Study start
- Sep 2003
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 22 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To test whether increasing the dose of imatinib or combining it with IFNalpha or ara-C increases the rate of molecular response (as measured by the decrease in BCR-ABL transcripts after 12 months of treatment) in patients with previously untreated CML in chronic phase.
To compare overall survival in a selected arm according to molecular response at 1 year from randomization with the reference arm.
Detailed description
Imatinib at 400 mg daily has emerged as the preferred therapy for newly diagnosed CML patients who do not undergo allogeneic stem cell transplant.
A phase III randomized study, comparing imatinib at 400 mg per day to interferon plus cytarabine in newly diagnosed chronic phase CML patients enrolled 1106 patients from June 2000 to January 2001. 553 patients were randomized to each treatment. For comparative purposes, at 6 months, 75% of patients randomized to imatinib obtained a major cytogenetic response with 51% complete responses. Despite these impressive results, only a minority of patients treated with imatinib in this study achieved a molecular remission. When analyzed by log reduction in Bcr-Abl transcript levels using quantitative RT-PCR, 39% of patients achieved a 3-log reduction in Bcr-Abl levels, but only 13% and 3% achieved a 4- and 5-log reduction, respectively.2 To improve upon these results, various groups have tried higher doses of imatinib, and combinations of imatinib with interferon alpha or cytarabine. Each of these studies has used cytogenetic responses as the major endpoint.
Each of these therapies has increased toxicity as compared to 400 mg of imatinib alone and the rates of molecular remissions have not been reported.
Thus the purpose of this study is to first determine whether higher doses of imatinib or combining Imatinib with interferon or Ara-C would result in higher rates of molecular responses and if so, in better survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Imatinib mesylate 400 mg | Experimental | Drug: Imatinib mesylate 400 mg, Drug: Imatinib mesylate 600 mg, Drug: Imatinib 400 mg + Peg-Interferon, Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 600 mg | Experimental | Drug: Imatinib mesylate 400 mg, Drug: Imatinib mesylate 600 mg, Drug: Imatinib 400 mg + Peg-Interferon, Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 400 mg +Peg interferon | Experimental | Drug: Imatinib mesylate 400 mg, Drug: Imatinib mesylate 600 mg, Drug: Imatinib 400 mg + Peg-Interferon, Drug: Imatinib mesylate 400 mg + Cytarabine |
| Imatinib mesylate 400 mg +Cytarabine | Experimental | Drug: Imatinib mesylate 400 mg, Drug: Imatinib mesylate 600 mg, Drug: Imatinib 400 mg + Peg-Interferon, Drug: Imatinib mesylate 400 mg + Cytarabine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients over 18 years of age
- Patients with Bcr-Abl positive CML in chronic phase.
- Patients within 14 weeks of diagnosis and previously untreated for CML except for hydroxyurea and/or anagrelide.
- No evidence of extramedullary leukemic involvement, with the exception of hepatosplenomegaly
- ECOG performance score of 0-2
Key exclusion criteria (3 listed)
- Depressive syndrome not controlled
- Uncontrolled medical illnesses.
- Women with childbearing potential and male patients who are unwilling or unable to use an adequate method to avoid pregancy for the entire period of the study
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 mesylate 400 mg | Drug | Imatinib mesylate 400 mg, Imatinib mesylate 400 mg +Cytarabine, Imatinib mesylate 400 mg +Peg interferon, Imatinib mesylate 600 mg |
| Imatinib mesylate 600 mg | Drug | Imatinib mesylate 400 mg, Imatinib mesylate 400 mg +Cytarabine, Imatinib mesylate 400 mg +Peg interferon, Imatinib mesylate 600 mg |
| Imatinib 400 mg + Peg-Interferon | Drug | Imatinib mesylate 400 mg, Imatinib mesylate 400 mg +Cytarabine, Imatinib mesylate 400 mg +Peg interferon, Imatinib mesylate 600 mg |
| Imatinib mesylate 400 mg + Cytarabine | Drug | Imatinib mesylate 400 mg, Imatinib mesylate 400 mg +Cytarabine, Imatinib mesylate 400 mg +Peg interferon, Imatinib mesylate 600 mg |
Primary outcome
Overall survival improvement
5 secondary outcomes
Molecular response improvement at 1 year
Time frame: 1 year
Hematological, cytogenetic responses improvement
Time frame: 1 year
Duration of responses improvement
Survival without progression improvement
Acceptable toxicity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2020.
- Derived from this study: PubMed 26474455Bruzzoni-Giovanelli H, Gonzalez JR, Sigaux F, Villoutreix BO, Cayuela JM, Guilhot J, Preudhomme C, Guilhot F, Poyet JL, Rousselot P. Genetic polymorphisms associated with increased risk of developing chronic myelogenous leukemia. Oncotarget. 2015 Nov 3;6(34):36269-77. doi: 10.18632/oncotarget.5915.
- Derived from this study: PubMed 24123600Delord M, Rousselot P, Cayuela JM, Sigaux F, Guilhot J, Preudhomme C, Guilhot F, Loiseau P, Raffoux E, Geromin D, Genin E, Calvo F, Bruzzoni-Giovanelli H. High imatinib dose overcomes insufficient response associated with ABCG2 haplotype in chronic myelogenous leukemia patients. Oncotarget. 2013 Oct;4(10):1582-91. doi: 10.18632/oncotarget.1050.
- Derived from this study: PubMed 24105694Johnson-Ansah H, Guilhot J, Rousselot P, Rea D, Legros L, Rigal-Huguet F, Nicolini FE, Mahon FX, Preudhomme C, Guilhot F. Tolerability and efficacy of pegylated interferon-alpha-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia. Cancer. 2013 Dec 15;119(24):4284-9. doi: 10.1002/cncr.28328. Epub 2013 Sep 16.
- Derived from this study: PubMed 21175313Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A, Rea D, Jourdan E, Allard C, Delmer A, Rousselot P, Legros L, Berger M, Corm S, Etienne G, Roche-Lestienne C, Eclache V, Mahon FX, Guilhot F; SPIRIT Investigators; France Intergroupe des Leucemies Myeloides Chroniques (Fi-LMC). Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med. 2010 Dec 23;363(26):2511-21. doi: 10.1056/NEJMoa1004095.
Related trials for Chronic Myeloid Leukemia
RecruitingPhase 1/2
Phase I/II Trial: Engineered Donor Graft (Orca Q) for Pediatric Hematopoietic Cell Transplant (HCT)
Acute Myeloid Leukemia, Acute Lymphoid Leukemia
RecruitingPhase 1
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Malignancy, Hematologic, Neoplasms, Hematologic
Not yet recruitingPhase 1
Allogeneic iNKT Cell Therapy (agenT-797) After SCT
Allogenic Stem Cell Transplantation, Myeloid Malignancies
RecruitingObservational study
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
Hematologic Malignancy, Leukemia
RecruitingPhase 1
Prophylactic DLI-X for Leukemia Relapse After HCT
Acute Lymphoid Leukemia, Acute Myeloid Leukemia
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.
François GUILHOT, MD study chair
Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imatinib mesylate 400 mg, Imatinib mesylate 600 mg and Imatinib 400 mg + Peg-Interferon in people with Chronic Myeloid Leukemia, run by Poitiers University Hospital at 1 site in France.
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 7 inclusion and 3 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 13 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall survival improvement. 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 NCT00219739, which also lists 4 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 13 Apr 2020.