Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients

Chronic Myeloid Leukemia Clinical Trial

— PETALs  

Official title:

Randomized Multicenter Phase III Study Comparing the Rate of Molecular Response 4.5 at 12 Months in Newly Diagnosed Philadelphia Positive Chronic Phase Chronic Myelogenous Leukemia Patients Receiving Either Frontline Nilotinib 600 mg Daily or Nilotinib 600 mg Daily Combined to Pegylated Interferon-alfa 2a (Peg-IFN)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02201459
• Other study ID #: 2013.837
• Status: Recruiting
• Phase: Phase 3
• First received: June 24, 2014
• Last updated: August 6, 2014
• Start date: August 2014
• Est. completion date: August 2019

Study information

• Verified date: August 2014
• Source: Hospices Civils de Lyon
• Contact: Madeleine ETIENNE, CRA
• Phone: 4 78 86 22 32
• Email: madeleine.etienne[@]chu-lyon.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

This is a phase III trial comparing, for newly diagnosed chronic phase CML patients, nilotinib 600 mg BID as a standard arm and nilotinib 600 mg BID combined to interferon alfa 2 a (pegylated form improving tolerance and maybe enhancing is efficacy) at increased doses for a total of 24 months of combination, in a 1:1 randomized manner. The assessment for the primary efficacy endpoint will be performed at 12 months (since nilotinib initiation) and is the rate patients obtaining MR4.5 will be measured at this time point.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: August 2019
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male and female patients

• CP-CML, positive Philadelphia chromosome or positive BCR-ABL (M-bcr transcript), diagnosed less than 3 months prior to study entry

• Age of at least 18 years-old and less than 65 years

• Patient for whom treatment with Nilotinib is expected

• No other CML treatment except for hydroxyurea and/or anagrelide

• No previous TKI treatment.

• No previous treatment with IFN even for other purposes.

• SGOT and SGPT < 2.5 UNL

• Serum creatinine < 2 UNL

• No planned allogeneic stem cell transplantation

• Signed informed consent

• ECOG score 0 to 2

Exclusion Criteria:

• Contra-indication to IFN

• Transcripts other than M-Bcr

• Pregnancy, lactation

• HIV positivity, chronic hepatitis B or C.

• Prior or concurrent malignancy other than CML (exceptions to be mentioned)

• History of arterial occlusive disease or (peripheral, carotids or severe coronary heart disease).

• Permanent elevation of total cholesterol and triglycerides despite treatment

• Severe psychiatric/neurological disease (previous or ongoing)

• Concomitant auto-immune disease

• Other investigational product ongoing

• Ongoing immunosuppressive treatment

• Ongoing treatment at risk for inducing torsades de pointes

• QTcF > 450ms despite correction of predisposing factors (i.e electrolytes…)

• Congenital long QTcF

• Unstabilised thyroid disorder

• No health insurance coverage

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid, Chronic-Phase

Intervention

Drug:
• Nilotinib (Tasigna ®), capsules of 150 mg
Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months
• Nilotinib (Tasigna ®) and Pegylated interferon alfa 2a (Pegasys®)
Nilotinib 2 capsules of 150 mg orally twice daily at 12 hours difference, fasting (minimum 1 hour before or 2 hours after a meal) for at least 36 months and Pegylated interferon alfa 2a subcutaneously once a week (auto-injection syringes of 135 and 90 micrograms) at 30 micrograms/week the first month alone (= priming procedure), then at 30 micrograms/2weeks the first month of combination to nilotinib and then at 45 micrograms/week thereafter until month 24 after nilotinib initiation.

Locations

Country	Name	City	State
France	Franck NICOLINI	Lyon

Sponsors (2)

Lead Sponsor	Collaborator
Hospices Civils de Lyon	Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Molecular response (MR) 4.5 at 12 months of nilotinib 300 mg twice a day versus a combination of low-dose Peg-Interferon (Peg-IFN) to nilotinib 300 mg twice a day in newly diagnosed CP-CML Chronic Phase Chronic Myelogenous Leukemia patients.	Centralised assessment of the BCR-ABL transcripts at 12 months since nilotinib initiation	12 months	No
Secondary	Molecular Response 4.5 at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MR4.5 during the second year of treatment (18, 24 and 36 months).	Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.	36 months	No
Secondary	Major Molecular Response at 1, 2, 3, 6, 9, 12 months of nilotinib, and duration of MMR during the second year of treatment (18, 24 and 36 months).	Centralised assessment of the BCR-ABL transcripts every month for 3 months and every three months until 12 months and thereafter every 6 months until 36 months assessment.	36 months	No
Secondary	Rate of patients with BCR-ABL/ABL (IS) =10% at 3 months.	Centralised assessment of the BCR-ABL transcripts at 3 months.	3 months after nilotinib initiation	No
Secondary	Rate of CCyR (complete cytogenetic responses: bone marrow Philadelphie positive at 0 % on at least 20 metaphases) at 3, 6, 12 months of nilotinib.	Local bone marrow cytogenetic assessment (on 20 metaphases)	Assessment at 3, 6 and 12 months	No
Secondary	Safety of the nilotinib combined to Peg-IFN or not (hematological and non-hematological adverse events (AE) graded according to the NCI CTC AE v3).	Continuous evaluation of the AEs and SAEs reported during 36 months	36 months	No
Secondary	Quality of life of patients treated in both arms	EORTC-QLQ C30 and C24 questionnaire at months -1 (Arm B), month 0, 1, 6, 12, 24, 36.	36 months	No
Secondary	Doses-reductions/interruptions of drugs in both arms. Mean daily doses of nilotinib and Peg-IFN administered.	Continuous recording of dose intensity along the study for 24-36 months.	24 months for Peg-IFN, and 36 months for both drugs	No
Secondary	Compliance to drugs in each arms	Morisky questionnaire to be fulfilled at 1, 6, 12, 24 and 36 months after nilotinib initiation.	36 months	No
Secondary	Molecular relapse rate at 6 and 12 months after nilotinib withdrawal in patients obtaining 2-year stable MR4.5.	Local (but standardized) assessment of the BCR-ABL transcripts every months for 3 months.	36 months	No
Secondary	Event-free survival.	Survival since randomization without any event defined as loss of CHR, loss of PCyR or CCyR, death from any cause, progression towards accelerated phase or blast crisis.	36 months	No
Secondary	Progression-free survival	Survival without progression towards accelerated of blast phase, death.	36 months	No
Secondary	Overall survival.	Survival without death from any cause	36 months	No