Addition of P1101 to Imatinib Treatment in Patients With Chronic Phase Chronic Myeloid Leukaemia Not Achieving a Complete Molecular Response

Phase 1 Study to Evaluate the Feasibility and Efficacy of the Addition of P1101 (PEG-Proline-Interferon Alpha-2b) to Imatinib Treatment in Patients With Chronic Phase Chronic Myeloid Leukaemia Not Achieving a Complete Molecular Response (MR 4.5 or BCR-ABL Transcripts Not Detectable)

In this phase I pilot study, it is planned to investigate the feasibility and safety of adding an interferon therapy to an preexisting imatinib treatment in patients with chronic phase chronic myeloid leukaemia. The participating patients have already reached a response during their imatinib therapy (CCyR) but have still a detectable disease (no molecular response MR 4.5 or better).

Study Overview

• Status: Completed
• Conditions: Chronic Phase Chronic Myeloid Leukemia
• Intervention / Treatment: Drug: P1101

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, A-6020
    • Universitätskliniken Innsbruck, Univ.-Klinik f.Innere Medizin V Hämtologie u. Onkologie
  • Linz, Austria, A-4020
    • Ordensklinikum Linz - Elisabethinen
  • Salzburg, Austria, 5020
    • Universitätsklinikum der PMU Salzburg, Universitätsklinik für Innere Medizin III
  • Oberösterreich
    • Wels, Oberösterreich, Austria, 4600
      • Klinikum Wels-Grieskirchen GmbH, IV. Interne Abteilung

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• BCR-ABL positive chronic myeloid leukaemia in chronic phase treated with imatinib as first line therapy
• CHR, CCyR after at least 18 months of imatinib treatment

• Adequate organ function, defined as the following:

  • total bilirubin < 1.5 x ULN,
  • AST and ALT < 2.5 x ULN,
  • creatinine < 1.5 x ULN,
  • ANC > 1.5 x 109/L,
  • platelets > 100 x 109/L
• Written, voluntarily signed informed consent

Exclusion Criteria:

• CMR (molecular remission 4.5 or BCR-ABL transcripts undetectable)
• Patient has received any other investigational treatment within 28 days before study entry
• Treatment with a second generation tyrosine kinase inhibitor (dasatinib, nilotinib)
• ECOG performance status ≥ 3
• Patients with a primary of a different histological origin than the study indication (unless relapse-free interval is ≥ 5 years, except cervical carcinoma, basal cell epithelioma or squamous cell carcinoma of the skin)
• Evidence of severe or uncontrolled systemic disease (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease etc.)
• Acute chronic infections
• Known autoimmune disease (e.g. collagen disease, polyarthritis, immune thrombocytopenia, thyroiditis, psoriasis, lupus nephritis or any other autoimmune disorder)
• Female patients who are pregnant or breast-feeding
• Known diagnosis of HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: P1101; P1101 50µg s.c. will be administered every 2 weeks in addition to preexisting imatinib treatment. In the absence of dose limiting toxicities after 12 weeks, the dose will be escalated to 100µg every 2 weeks. Maximum treatment duration will not expand 18 months.	Drug: P1101; Other Names: PEG-Proline-Interferon alpha-2b

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and seriousness of adverse events to evaluate safety and tolerability	The primary objective is to determine the safety and tolerability of the addition of P1101 to the pre-study established dose of imatinib.	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy (Number of patients achieving an improvement of remission status)	Secondary objective is to determine the rate of achievement of ≥ 1 log reduction from the initial BCR-ABL transcript level at study entry and the achievement of molecular remission 4.5 or undetectable BCR-ABL transcripts.	30 months

Collaborators and Investigators

• Sponsor: Arbeitsgemeinschaft medikamentoese Tumortherapie
• Collaborators: AOP Orphan Pharmaceuticals AG

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2013
• Primary Completion (Actual): November 14, 2018
• Study Completion (Actual): November 14, 2018

Study Registration Dates

• First Submitted: August 29, 2013
• First Submitted That Met QC Criteria: August 29, 2013
• First Posted (Estimate): September 2, 2013

Study Record Updates

• Last Update Posted (Actual): January 4, 2019
• Last Update Submitted That Met QC Criteria: January 3, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: P1101; CML; Interferon; Imatinib; Chronic myeloid leukemia; Chronic myeloid leukaemia; PEG-Proline-Interferon-alpha 2b
• 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; Leukemia, Myeloid, Chronic-Phase; 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: AGMT_CML 1; 2013-000115-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No