STI571 ProspectIve RandomIzed Trial: SPIRIT (SPIRIT)

April 10, 2020 updated by: Poitiers University Hospital

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

789

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Poitiers, France, 86021
        • University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 600 mg
Drug: Imatinib 400 mg + Peg-Interferon
Drug: Imatinib mesylate 400 mg + Cytarabine
Experimental: Imatinib mesylate 600 mg
Drug: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 600 mg
Drug: Imatinib 400 mg + Peg-Interferon
Drug: Imatinib mesylate 400 mg + Cytarabine
Experimental: Imatinib mesylate 400 mg +Peg interferon
Drug: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 600 mg
Drug: Imatinib 400 mg + Peg-Interferon
Drug: Imatinib mesylate 400 mg + Cytarabine
Experimental: Imatinib mesylate 400 mg +Cytarabine
Drug: Imatinib mesylate 400 mg
Drug: Imatinib mesylate 600 mg
Drug: Imatinib 400 mg + Peg-Interferon
Drug: Imatinib mesylate 400 mg + Cytarabine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Overall survival improvement

Secondary Outcome Measures

Outcome Measure
Time Frame
Molecular response improvement at 1 year
Time Frame: 1 year
1 year
Hematological, cytogenetic responses improvement
Time Frame: 1 year
1 year
Duration of responses improvement
Survival without progression improvement
Acceptable toxicity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Poitiers University Hospital

Collaborators

Novartis
Roche Pharma AG
Ministry of Health, France

Investigators

  • Study Chair: François GUILHOT, MD, Department of Oncology hematology and Cell therapy, University Hospital , 86021 Poitiers - FRANCE

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2003

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

September 13, 2005

First Submitted That Met QC Criteria

September 13, 2005

First Posted (Estimate)

September 22, 2005

Study Record Updates

Last Update Posted (Actual)

April 13, 2020

Last Update Submitted That Met QC Criteria

April 10, 2020

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SPIRIT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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