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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Myelogenous Leukemia
• Intervention / Treatment: Biological: Pegylated interferon alfa-2b; Biological: Interferon alfa-2b

• Study Type: Interventional
• Enrollment (Actual): 344
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pegylated interferon alfa-2b; 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; Weekly SC injection of pegylated interferon alfa-2b, 6.0 microg/kg; Other Names: PEG Intron
Active Comparator: Interferon alfa-2b; 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; Daily SC injection of interferon alfa-2b, 5 MIU/m^2; Other Names: INTRON^® A

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 1998
• Primary Completion (Actual): February 20, 2001
• Study Completion (Actual): February 20, 2001

Study Registration Dates

• First Submitted: May 24, 2018
• First Submitted That Met QC Criteria: May 24, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): August 12, 2019
• Last Update Submitted That Met QC Criteria: July 12, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2b
• Other Study ID Numbers: C98026; MK-4031-001 (Other Identifier: Merck Protocol Number); C98-026 (Other Identifier: Schering-Plough)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No