Polyethylene Glycol Interferon Alfa-2b (PEG Intron) Versus Interferon Alfa-2b (INTRON^® A) in the Treatment of Newly Diagnosed Chronic Myelogenous Leukemia (CML) (C98026)

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the efficacy of polyethylene glycol (PEG; pegylated) interferon alfa-2b (PEG Intron, C98026) versus interferon alfa-2b (Intron® A) in the treatment of participants with newly diagnosed CML.

Official Title
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A RANDOMIZED PHASE 2/3 TRIAL OF SCH 54031 PEG12000 INTERFERON ALFA-2b (PEG INTRON, SCH 54031) VS. INTRON A (SCH 30500) IN SUBJECTS WITH NEWLY DIAGNOSED CML (PROTOCOL NOS. C/I98-026)

Conditions
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Chronic Myelogenous Leukemia

Intervention / Treatment
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* Biological: Pegylated interferon alfa-2b
* Biological: Interferon alfa-2b


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Has chronic phase CML diagnosed within 3 months prior to study enrollment Has chronic phase CML positive for Ph^1 as confirmed by cytogenetic studies, performed by a central laboratory Has platelet count >/= 50,000/microl Has hemoglobin >/= 9.0 g/dL Has WBC count >/=2000/microl but </= 50,000/microl Has adequate hepatic and renal function, as defined by the following parameters obtained within 14 days prior to initiation of study treatment serum glutamic oxaloacetic transaminase (SGOT) <2 times upper limit of laboratory normal (ULN) serum glutamic pyruvic transaminase SGPT <2 times upper ULN serum bilirubin <2 times ULN serum creatinine <2.0 mg/dL Is fully recovered from any prior major surgery and must be at least 4 weeks postoperative Has Eastern Cooperative Oncology Group Performance Status of 0-2 Has signed a written, voluntary informed consent before study entry, is willing to participate in this study, and is willing to complete all follow-up assessments Exclusion Criteria: Has accelerated phase CML as defined by any of the following criteria. peripheral blood myeloblasts >/=15% peripheral blood basophils >/= 20% peripheral blood myeloblasts plus promyelocytes >/=30% platelets <100,000/microl, unrelated to therapy Has blastic phase CML (30% myeloblasts in peripheral blood or bone marrow) Is a candidate for and is planning to receive allogeneic, syngeneic, or autologous bone marrow transplantation within the next 12 months Has received prior treatment for their CML, except for hydroxyurea (collection of stem cells without using high dose chemotherapy for mobilization is acceptable) Has severe cardiovascular disease (i. e., arrhythmias requiring chronic treatment, congestive heart failure [New York Heart Association (NYHA) Class III or IV], or symptomatic ischemic heart disease) Has a history of a neuropsychiatric disorder requiring hospitalization Has thyroid dysfunction not responsive to therapy Has uncontrolled diabetes mellitus Has a history of seropositivity for human immunodeficiency virus Has active and/or uncontrolled infection, including active hepatitis Has a medical condition requiring chronic systemic corticosteroids Has a history of prior malignancies within the last 5 years, except for surgically cured non-melanoma skin cancer, or cervical carcinoma in situ Has received any experimental therapy within 30 days prior to enrollment in this study Is known to be actively abusing alcohol or drugs Is pregnant, nursing, or of reproductive potential and is not practicing an effective means of contraception

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegylated interferon alfa-2b<br>Participants received pegylated interferon alfa-2b (PEG Intron) at a dose of 6.0 microg/kg, administered weekly by subcutaneous (SC) injection. Participants may have received hydroxyurea therapy as needed prior to randomization to reduce or keep the white blood cell (WBC) count ≤50,000/μl. Treatment was for a minimum of 6 months unless there was evidence of disease progression or unacceptable toxicity. | Biological: Pegylated interferon alfa-2b<br>* Weekly SC injection of pegylated interferon alfa-2b, 6.0 microg/kg<br>* Other names: PEG Intron;|
| Active Comparator: Interferon alfa-2b<br>Participants received interferon alfa-2b (Intron^® A), recombinant for injection, at a dose of 5 million international units (MIU)/m^2, administered daily by SC injection. Participants may have received hydroxyurea therapy as needed prior to randomization to reduce or keep the WBC count ≤50,000/μl. Treatment was for a minimum of 6 months unless there was evidence of disease progression or unacceptable toxicity. | Biological: Interferon alfa-2b<br>* Daily SC injection of interferon alfa-2b, 5 MIU/m^2<br>* Other names: INTRON^® A;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cytogenetic Responses to PEG Intron and INTRON A at 12 Months | Cytogenetic response (CR) was defined by the degree of suppression of Philadelphia chromosome (Ph^1) achieved during study treatment. For all participants continuing treatment after study conclusion, cytogenetic assessments were conducted locally as per standard of care. Determination of CR at 12 months were based on cytogenetic analysis of bone marrow aspirate samples. The CR criteria were based on the percentage (%) of PH^1-positive cells during study treatment. Protocol-defined CR criteria were Complete Response (0%), Partial Response (1-34%), Minor Response (35-90%), or No Response (>90%). Data for the analysis population was based on the intent-to-treat principle. Participants who were treatment failures at 6 months were considered cytogenetic non-responders. Recording of CR was independent of hematologic responses. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cytogenetic Response (CR) to PEG Intron and Intron A at 6 Months | Cytogenetic response (CR) at 6 months, as at 12 months, was defined by the degree of suppression of Philadelphia chromosome (Ph^1) achieved during study treatment. The determination of CR at 6 months was based on cytogenetic analysis of bone marrow aspirate samples. The CR criteria were based on the percentage (%) of PH^1-positive cells during study treatment. Protocol-defined CR criteria were Complete (0%), Partial (1-34%), Minor (35-90%), or No Response (>90%). Data for the analysis population was based on the intent-to-treat principle. Participants who were treatment failures at 6 months were considered cytogenetic non-responders. Recording of CR was independent of hematologic responses. | 6 months | 
| Number of Participants With Hematologic Responses to PEG Intron and Intron A at 6 Months | Hematologic response at 6 months was assessed, while the hematologic response was measured at 3, 6, 9 and 12 months during the first year of study treatment. To be considered a hematologic responder a participant must have met all of the following criteria for a minimum of 28 days: WBC count <10,000/μL; platelet count <450,000/L; normal differential count in peripheral blood (manual differential count); no palpable spleen. Participants achieving a complete hematologic response at 3 months had the cytogenetic response evaluated at 3 months as well. Participants who achieved a complete hematologic response by 6 months continued treatment for another 6 months. Participants who failed to achieve a complete hematologic response after 6 months of treatment were considered treatment failures, and further treatment for this group was at the discretion of the treating physician. Participants may have continued to receive their assigned study medication for an additional 6 months. | 6 months | 
| Number of Participants With Overall Survival | Participants were followed for survival; those who did not achieve a major cytogenetic response were discontinued from the study. For participants who completed 1 year of study treatment and continued to Year 2 and beyond, survival and disease progression every 3 months were assessed, and serious adverse events (SAEs) were reported. Participants were followed until resolution of any drug-related nonserious adverse event, and any SAE occurring while on the study or within 30 days of last dose of study drug. Participant death during survival follow-up was reported to the drug safety unit of the Sponsor. Each participant (whether discontinued or still on treatment) was followed every 3 months for survival and disease progression information. Overall survival was analyzed using the log-rank statistic, and the hazard ratio (HR) and 95% confidence interval (CI) for the HR were obtained using Cox's proportional hazards model. | Up to 2 years (24 months), and beyond |