Phase II trial of Pegasys in Glivec responsive chronic phase chronic myeloid leukaemia

Phase 2

Completed

• Conditions: Chronic myeloid leukaemia; Cancer - Leukaemia - Chronic leukaemia

• Registration Number: ACTRN12605000041651
• Lead Sponsor: Australasian Leukaemia and Lymphoma Group

Brief Summary

Alpha-interferon (IFN) based therapy was formerly standard initial therapy for de novo CP CML not immediately proceeding to allograft. While producing survival benefit and CCR rate of 10-30%. IFN was associated with substantial early and late toxicity, low molecular remission rate (<5%) and threat of late relapse including blast crisis. Imatinib has become the standard of care and produces significantly greater reduction in bcr-abl in de novo CML. The ALLG explored Imatinib in 22 longstanding IFN treated CP patients in CCR or near CCR (<10% Ph+ve metaphases). Patients had been in CCR/near CCR for 30 months (6-117) and were 63 (22-176) months from diagnosis. IFN was stopped and Imatinib 400mg daily commenced. Patients were assessed for toxicity and efficacy with serial 3 monthly bone marrow cytogenetic and quantitative bcr-abl/bcr analysis on peripheral blood and marrow. No patients experienced significant toxicity with Imatinib being well tolerated. 15 patients (12- CCR, 3 – near CCR) are assessable following 9 months of Imatinib therapy: six patients have achieved molecular remission (peripheral blood bcr-abl/bcr analysis) while three patients have reduced levels and six patients stable levels on peripheral blood bcr-abl/bcr analyses since study commencement. This latter group tended to contain those who have already exhibited major molecular response on Interferon whereas patients who achieved molecular remission or significant reduction tended to be those who had not achi

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2005-07-25
• Study Completion: 2015-01-12
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

All of the following criteria must be met: Cohort One: 1. Chronic Myeloid Leukemia with Philadelphia chromosome translocation or bcr-abl transcript at diagnosis; 2. Treated with Glivec®, as a single agent at 600 mg or maximum tolerated dose for at least 6 months; 3. Achieved complete cytogenetic response on Glivec® therapy AND not previously in accelerated phase or blast crisis; 4. Sustained complete cytogenetic response for at least 6 months, confirmed by bone marrow studies at screening visit for this study; 5. No past toxicity higher than Grade III related to high dose (>6MU/d) alpha- interferon therapy. No post toxicity higher than Grade II related to low dose (3MU/day or less) alpha-interferon therapy; 6. Persisting detectable bcr/abl transcripts by Q-PCR. 7. Patients must have adequate renal function i.e creatinine < 2 xULN 8. Adequate hepatic function, with serum bilirubin, AST and ALT each < 2 x the upper limit of their normal range (ULN) at the laboratory where the analyses were performed.
Cohort Two: 1. Chronic Myeloid Leukemia with Philadelphia chromosome translocation or bcr-abl transcript at diagnosis; 2. Treated with Glivec®, as a single agent at 600 mg or maximum tolerated dose for at least 6 months; 3. Achieved near complete cytogenetic response on Glivec® therapy OR Achieved a complete cytogenetic response on Glivec® therapy AND previously in accelerated phase or blast crisis; 4. Sustained complete or near-complete cytogenetic response for at least 6 months, confirmed by bone marrow studies at screening visit for this study; 5. No past toxicity higher than Grade III related to high dose (>6MU/d) alpha-interferon therapy. No post toxicity higher than Grade II related to low dose (3MU/day or less) alpha-interferon therapy; 6. Persisting detectable bcr/abl transcripts by Q-PCR. 7. Patients must have adequate renal function i.e creatinine < 2 xULN 8. Adequate hepatic function, with serum bilirubin, AST and ALT each < 2 x the upper limit of their normal range (ULN) at the laboratory where the analyses were performed;

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess whether adding interferon to imatinib in these patients improves molecular response status (by PCR quantification of bcr-abl transcripts)[Measured in 18 months]

Secondary Outcome Measures

Name	Time	Method
To assess the safety of treatment with interferon in such CML patients, who have had complete or near complete cytogenetic response to imatinib therapy.[Outcome will be measured in 18 months.]