A Study of Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms

NCT01387763 | Completed Phase 3 DMC

• 1 other identifier: daliah2011
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the study is to compare the efficacy and toxicity including quality of life of two types of low-dose interferon alpha compounds (PegIntron and Pegasys) with hydroxyurea (Hydrea), and to investigate the occurence of neutralizing antibodies against recombinant interferon.

Conditions

Polycythemia Vera; Essential Thrombocythemia; Primary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• molecular response (changes from baseline)

  Molecular responses (JAK V617F allele burden) are assessed by qPCR according to the ELN guidelines.

  18, 36 and 60 months

Secondary Outcomes (6)

• toxicity (discontinuation of therapy due to intolerability)

  18 months

• Quality of life (changes from baseline)

  4, 12, 24, 36, 48 and 60 months

• Histopathological response (changes from baseline)

  36 and 60 months

• Sustained molecular response (changes from level at time of discontinuation of therapy)

  12, 24 and 36 months

• Neutralizing antibodies against PegIntron and Pegasys

  24 months

Study Arms (5)

PegIntron <= 60 years

ACTIVE COMPARATOR

In patients \<= 60 years PegIntron is started at low-dose 35 micrograms once weekly. Dose escalation to 50 micrograms weekly if lack of complete hematological response at 4 months or lack of at least partial molecular response at 8 months. If complete hematological response or lack of at least partial molecular response is not achieved at 50 micrograms weekly at 12 months and 18 months respectively, dose escalation to 96 micrograms weekly.

Drug: PegIntron

Pegasys <= 60 years

ACTIVE COMPARATOR

In patients \<= 60 years Pegasys is started at low-dose 45 micrograms once weekly. Dose escalation to 90 micrograms weekly if lack of complete hematological response at 4 months or lack of at least partial molecular response at 8 months. If complete hematological response or lack of at least partial molecular response is not achieved at 90 micrograms weekly at 12 months and 18 months respectively, dose escalation to 135 micrograms weekly.

Drug: Pegasys

PegIntron > 60 years

ACTIVE COMPARATOR

In patients \< 60 years PegIntron is started at low-dose 35 micrograms once weekly. Dose escalation to 50 micrograms weekly if lack of complete hematological response at 4 months or lack of at least partial molecular response at 8 months. If complete hematological response or lack of at least partial molecular response is not achieved at 50 micrograms weekly at 12 months and 18 months respectively, dose escalation to 96 micrograms weekly.

Drug: PegIntron

Pegasys > 60 years

ACTIVE COMPARATOR

In patients \> 60 years Pegasys is started at low-dose 45 micrograms once weekly. Dose escalation to 90 micrograms weekly if lack of complete hematological response at 4 months or lack of at least partial molecular response at 8 months. If complete hematological response or lack of at least partial molecular response is not achieved at 90 micrograms weekly at 12 months and 18 months respectively, dose escalation to 135 micrograms weekly.

Drug: Pegasys

Hydroxyurea > 60 years

ACTIVE COMPARATOR

Capsule Hydrea 500-2000 mg orally QD or BID

Drug: Hydrea

Interventions

PegIntron DRUG

PegIntron, prefilled syringe 50 micrograms/0.5 ml. 30 micrograms subcutaneously once weekly.

Also known as: Pegylated interferon alpha 2b

PegIntron <= 60 years

Pegasys DRUG

Pegasys, prefilled syringe 180 micrograms/0.5 ml 45 micrograms subcutaneously once weekly

Also known as: Pegylated interferon alpha 2a

Pegasys <= 60 years

Hydrea DRUG

Capsule Hydrea 500-2000 mg orally QD or BID

Also known as: hydroxyurea, hydroxycarbamide

Hydroxyurea > 60 years

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female \> 18 years of age
• Newly diagnosed, or previously diagnosed untreated patients with ET, PV or PMF including prefibrotic myelofibrosis according to the WHO classification
• Active disease defined by one of the following criteria:
• need for phlebotomy
• leukocytosis \> 10 mia/l
• thrombocytosis \> 400 mia/l
• constitutional symptoms (fatigue, weight loss, night sweats or fewer \> 38 degrees celsius)
• Pruritus
• splenomegaly causing symptoms
• previous thrombosis

You may not qualify if:

• Fertile women without a negative pregnancy test
• Other malignant disease within last 5 years
• ECOG performance score \>/= 3
• Creatinine \> 2x ULN
• Bilirubin \> 1.5x ULN
• ALAT \> 3x ULN
• Previous psychiatric disorder (depression)
• active autoimmune disease
• Uncontrolled thyroid disease

Sponsors & Collaborators

• Thomas Stauffer Larsen: lead

Study Sites (8)

Dept of Hematology, Aalborg hospital

Aalborg, 9000, Denmark

Location

Dept. of Hematology, Aarhus University Hospital

Aarhus, 8000, Denmark

Location

Dept of Hematology, Rigshospitalet

Copenhagen, 2100, Denmark

Location

Dept of Hematology, Esbjerg Hospital

Esbjerg, 6700, Denmark

Location

Dept of Hematology, Herlev Hospital

Herlev, 2730, Denmark

Location

Dept of Hematology, Holstebro Hospital

Holstebro, 7500, Denmark

Location

Dept of hematology, Odense University Hospital

Odense, 5000, Denmark

Location

Dept. of Hematology, Roskilde Hospital

Roskilde, 4000, Denmark

Location

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

peginterferon alfa-2b; peginterferon alfa-2a; Hydroxyurea

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Thomas S Larsen, MD PhD

  Dept. of Hematology, Odense University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD PhD

Study Record Dates

• First Submitted: June 23, 2011
• First Posted: July 6, 2011
• Study Start: January 1, 2012
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

DK (8)