ENDURE - Efficacy and Safety of AOP2014 With CML Patients in Remission

NCT03117816 | Completed Phase 3 DMC

• 2 other identifiers: KKS-2272016-001030-94
• Study Type: interventional
• Target: 214
• Locations: 2 countries
• Sites: 26

Brief Summary

A randomized, open-label assessor blinded, multi-center, controlled phase III Trial to evaluate the efficacy of AOP2014 administered bi-weekly subcutaneously (s.c.) in preventing molecular relapse (loss of MMR) in CML patients, who discontinue ABL tyrosine kinase inhibitor therapy (TKI) in deep molecular remission of MR4 or better (MR4.5, or MR5).

Conditions

Chronic Myeloid Leukemia in Remission

Keywords

deep molecular remission of MR4 or better

Outcome Measures

Primary Outcomes (1)

• mRFS

  The primary efficacy endpoint is molecular relapse free survival (mRFS). Relapse is defined as loss of major molecular remission, MMR, which is any increase of the BCR-ABL ratio to \> 0.1% according to the international scale (IS). Time to relapse is defined as the time from randomization to relapse the BCR-ABL ratio to \> 0.1% according to the international scale (IS). Time to relapse is defined as the time from randomization to relapse.

  Randomization until time of relapse

Secondary Outcomes (11)

• mRFS 7

  7 months after randomization

• mRFS 13

  13 months after randomization

• mRFS 25

  25 months after randomization

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

  Day 0 - Month 15 (Arm B) or Month 16 (additional safety visit one month after last application for Arm A)

• Quality of life measured by EORTC QLQ-C30

  Day 0 - Month 25

Study Arms (2)

investigational arm A

EXPERIMENTAL

There will be an overlapping treatment with AOP2014 and TKI for one month. After one month, the TKI therapy will be stopped and patient will receive only AOP2014 treatment for the next 14 months.

Drug: AOP2014 / Pegylated-Proline-interferon alpha-2b

surveillance arm B

OTHER

This is an open-label study with a "surveillance" group as comparator arm. Similar as in the arm A, patient will discontinue TKI therapy one month after randomization. From then on patient will receive no further CML treatment.

Other: Surveillance

Interventions

AOP2014 / Pegylated-Proline-interferon alpha-2b DRUG

AOP2014 as pre-filled auto-injection pen for subcutaneous injection, containing 250 µg AOP2014 / 0.5 ml. The solution also contains inactive ingredients (sodium chloride, polysorbate 80, benzyl alcohol, sodium acetate, and acetic acid). The solution is colorless to light yellow.

investigational arm A

Surveillance OTHER

For patients randomized into this treatment arm stopp their standard treatment and will just be under observation.

surveillance arm B

Eligibility Criteria

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

You may qualify if:

• Signed written informed consent form.
• Capability and willingness to comply with study procedures and ability to self-administration of the study drug.
• Male or female aged ≥ 18 years.
• At least three years of TKI therapy.
• BCR-ABL-positive, chronic phase CML patients with a transcript level according to the international scale (IS) of at least MR4, or better (MR4.5, MR5). MR4 is defined as (i) detectable disease ≤0.01% BCR-ABL IS or (ii) undetectable disease in cDNA with ≥10,000 ABL or ≥24,000 GUS transcripts for at least one year. There have to be at least three consecutive PCR-results with MR4 or better within the last year (+ months) before study entry. The latest of these PCRs must be a confirmatory MR4 measurement prior to randomization by the EUTOS-certified Study Reference Laboratories for PCR (BCR-ABL mRNA). No PCR-results in the last year before randomisation can be worse than MR4. If the last PCR was not done within two months from baseline (day 0) in an EUTOS-certified study Reference Laboratory; the PCR sample must be sent to an EUTOS-certified study Reference Laboratory at screening.
• Adequate organ function:
• especially total bilirubin, lactate dehydrogenase \[LDH\], aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\] and coagulation parameters ≤ 2 × upper limit of normal (ULN)
• Adequate hematological parameters:
• platelet count ≥ 100 × 1000000000/L; white blood cell count ≥ 2.5 × 1000000000/L; lymphocytes ≥ 1.0 × 1000000000/L; hemoglobin ≥ 9.0 g/dL or 5.59 mmol/L.
• Female patients with reproductive potential must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used. Male patients must agree to use condoms during study participation.
• Negative serum pregnancy test in women of childbearing potential.
• Date of diagnosis of CML confirmed by laboratory PCR must be known.

You may not qualify if:

• Rare variants of BCR-ABL not quantifiable by RT-PCR according to the international scale (IS).
• Current or previous autoimmune diseases requiring treatment.
• Immunosuppressive treatment of any kind; transplant recipients
• Prior allogeneic stem cell transplantation.
• Prior pegylated IFN therapy. Prior low dose conventional IFN treatment with ≤ 3 x 3 Mio I.E. / week for less than 1 year is acceptable.
• History of TKI resistance within the last 4 years of TKI therapy.
• History of accelerated phase or blast crisis.
• Hypersensitivity/allergy to the active substance or excipients of the formulation.
• Severe hepatic dysfunction or decompensated cirrhosis.
• End stage renal disease (GFR \<15 ml/min)
• Thyroid disease that cannot be controlled by conventional therapy.
• Uncontrolled diabetes mellitus
• Epilepsy or other disorders of the central nervous system.
• Severe cardiac disease history including unstable or uncontrolled cardiac disease in the previous 6 months.
• Uncontrolled hypertension

Sponsors & Collaborators

• Philipps University Marburg: lead
• Deutsche Krebshilfe e.V., Bonn (Germany): collaborator
• AOP Orphan Pharmaceuticals AG: collaborator

Study Sites (26)

Institut Bergonié

Bordeaux, 33076, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

CHRU de Nancy - Hôpitaux de Brabois

Vandœuvre-lès-Nancy, 54500, France

Location

03 Universitätsklinikum Aachen, Hämatologie/Onkologie

Aachen, 52074, Germany

Location

18 Studienzentrum Aschaffenburg

Aschaffenburg, 63739, Germany

Location

06 Universitätsmedizin Berlin Charite- Campus Virchow Klinikum, Klinik für Hämatologie und Onkologie

Berlin, 13353, Germany

Location

19 Universitätsklinikum Bonn, Medizinische Klinik und Poliklinik III

Bonn, 53105, Germany

Location

16 Klinikum Bremen Mitte, Medizinische Klinik I

Bremen, 28177, Germany

Location

22 BAG / Onkologische Gemeinschaftspraxis

Dresden, 01307, Germany

Location

05 Universitätsklinikum Düsseldorf, Klinik für Hämatologie, Onkologie und Klinische Immunologie

Düsseldorf, 40225, Germany

Location

07 Universitätsklinikum Erlangen, Medizinische Klinik 5

Erlangen, 91054, Germany

Location

20 Universitätsklinikum Essen, Klinik für Hämatologie

Essen, 45147, Germany

Location

17 Klinikum der Goethe Universität, Medizinische Klinik II

Frankfurt A. Main, 60590, Germany

Location

21 Universitätsklinikum Hamburg Eppendorf, Klinik für Onkologie, Hämatologie und KMT

Hamburg, 20246, Germany

Location

23 Evangelische Krankenhaus Hamm gGmbH, Klinik für Hämatologie, Onkologie und Palliativmedizin

Hamm, 59063, Germany

Location

02 Universitätsklinikum Jena, linik für Innere Medizin II Abt. für Hämatologie und Internistische Onkologie

Jena, 07740, Germany

Location

24 Institut für Versorgungsforschung in der Onkologie GbR

Koblenz, 56068, Germany

Location

13 Universitätsklinikum Leipzig, Abteilung für Hämatologie u. Internistische Onkologie

Leipzig, 04103, Germany

Location

14 Johannes-Gutenberg-Universität III. Medizinische Klinik

Mainz, 55131, Germany

Location

04 Universitätsmedizin Mannheim, III. Medizinische Klinik

Mannheim, 68169, Germany

Location

01 Universitätsklinikum Gießen und Marburg GmbH, Standort Marburg, Klinik für Hämatologie, Onkologie und Immunologie

Marburg, 35043, Germany

Location

10 Technische Universität München (TUM) Klinikum rechts der Isar, III. Medizinische Klinik und Poliklinik

Munich, 81675, Germany

Location

08 Universitätsklinikum Münster, Medizinische Klinik, Innere Medizin A

Münster, 48149, Germany

Location

09 Universitätsklinikum Tübingen, Medizinische Klinik

Tübingen, 72076, Germany

Location

12 Universitätsklinikum Ulm, Klinik für Innere Medizin III

Ulm, 89081, Germany

Location

15 Universitätsklinikum Würzburg, Zentrum für Innere Medizin

Würzburg, 97080, Germany

Location

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Study Officials

• Andreas Burchert, Prof. Dr.

  Philipps University Marburg

  STUDY DIRECTOR

• Franck E Nicoloni, MD, PhD

  Centre Léon Bérard, Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: A randomized, open-label assessor blinded, multi-center, controlled phase III trial
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: KKS Marburg Sponsor representative

Study Record Dates

• First Submitted: March 8, 2017
• First Posted: April 18, 2017
• Study Start: May 4, 2017
• Primary Completion: January 26, 2022
• Study Completion: December 12, 2022
• Last Updated: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (3); DE (23)