An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years

NCT02174445 | Terminated Phase 3

• 3 other identifiers: CAMN107ADE18T2013-000077-68DRKS00006285
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 18

Brief Summary

This is an open-label, multicenter, randomised phase 3b clinical trial of Imatinib 400 to 800 mg daily versus Nilotinib 300 mg two times daily in chronic phase CML patients with confirmed MMR without MR4.5

Conditions

Chronic Myeloid Leukemia

Keywords

Patients with CML in chronic phase; Imatinib; Nilotinib

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with confirmed MR4 after two years of study treatment

  Proportion of patients with confirmed MR4 at two years of study treatment in both treatment arms. Confirmed MR4 at two years is defined as either BCR-ABL ≤ 0.01% IS at 21 and 24 months or BCR-ABL ≤ 0.01% IS at 24 months and confirmation within six weeks

  2 years

Study Arms (2)

Imatinib

EXPERIMENTAL

Imatinib 400-800mg, daily, maximum 6 years

Drug: Imatinib

Nilotinib

ACTIVE COMPARATOR

Nilotinib, 300mg, twice daily, maximum 6 years

Drug: Nilotinib

Interventions

Imatinib DRUG

Imatinib, 400 to 800 mg p.o., daily

Also known as: Glivec

Imatinib

Nilotinib DRUG

300mg p.o., twice-daily

Also known as: Tasigna

Nilotinib

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
• Male or female patients aged \>=18 years (without upper limit of age)
• ECOG performance status of 0 to 2
• CML in chronic phase, with chronic phase defined as blasts \< 15% in blood and/or bone marrow and peripheral blood basophils \< 20% and platelets ≥ 100 G/L
• Pretreatment with Imatinib with a treatment duration of at least 18 months at a dosage of 400 to 800 mg daily
• Major molecular response (MMR) without molecular response ≥ 4.5 log (MR4.5), i.e. BCR-ABL\>0.0032% and ≤0.1% IS confirmed by central la-boratory at screening will be required for randomisation
• Patients must have a serum Creatinine of ≤ 1.5 x ULN, SGOT ≤ 1.5 x ULN, total bilirubin ≤ 1.5 x ULN (except known M. Gilbert), and Lipase ≤ 1.5 x ULN
• Women of child-bearing potential defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months, must have a negative serum pregnancy test during screening period. Male and fe-male patients of reproductive potential must agree to employ highly ef-fective methods of birth control throughout the study and for up to 3 months following discontinuation of study drug. Appropriate methods are e.g. a highly effective method of first choice, i.e. a method with a low failure rate (less than 1% per year) like sexual abstinence, com-bined oral contraceptives, implants, injectable, some Intra Uterine Devices (IUDs), vasectomized partner, in combination with a method of second choice like condom, diaphragm, or cup pessary with spermicidal foam/gel/film/cream/suppository.

You may not qualify if:

• Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha
• Evidence of features of accelerated or blast phase at any time
• Previous loss of hematologic or cytogenetic response
• Concomitant medications known to be strong inducers or inhibitors of P450 Isoenzyme CYP3A4
• Finding of a secondary BCR-ABL resistance mutation at any time
• History of intolerance to Imatinib that required treatment interruption longer than 4 weeks (cumulative) or dose reductions to less than 400 mg daily for longer than 4 weeks (cumulative) during the last 12 months before informed consent
• Patients who had prior allogeneic, syngeneic, or autologous bone mar-row transplant or stem cell transplant
• Patients unwilling to or unable to comply with the planned therapeutic intervention or to comply with the study treatment visits including blood sample collection within the protocol
• History of pancreatitis, chronic inflammatory diseases or autoimmune diseases
• Patients who underwent solid organ transplantation
• Impaired cardiac function, including any of the following:
• History of or presence of complete left bundle branch block, right bundle branch block plus left anterior hemi block, bifascicular block in screening ECG
• Use of a cardiac pacemaker
• ST depression of \> 1mm in 2 or more leads and/or T wave inver-sions in 2 or more contiguous leads in screening ECG
• Congenital Long QT Syndrome

Sponsors & Collaborators

• Prof. Dr. Nikolas von Bubnoff: lead
• Novartis: collaborator

Study Sites (18)

Universitätsklinikum Aachen

Aachen, 52074, Germany

Location

Praxis Dr. Bruder / Dr. Heinrich / Prof. Bangerter

Augsburg, 86150, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Universitätsklinik Köln

Cologne, 50937, Germany

Location

Gemeinschaftspraxis

Dresden, 01307, Germany

Location

Praxis Dr. Hauch

Erfurt, 99084, Germany

Location

Internistische Schwerpunktpraxis Erlangen oncosearch

Erlangen, 91052, Germany

Location

Praxis für Hämatologie/Onkologie Dres. Rudolph, Sengpiel, von Verschuer

Essen, 45136, Germany

Location

University Medical Center

Freiburg im Breisgau, 79106, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Jena

Jena, 07747, Germany

Location

Gemeinschaftspraxis Hämatologie/Onkologie

Magdeburg, 39104, Germany

Location

Klinikum Mannheim GmbH Universitätsklinikum

Mannheim, 68167, Germany

Location

Überörtliche Gemeinschaftspraxis Hämato-Onkologie Pasing/Fürstenfeldbruck

Munich, 81241, Germany

Location

Klinikum rechts der Isar, Technische Universität München

München, 81675, Germany

Location

Onkologische Praxis Oldenburg

Oldenburg, 26121, Germany

Location

Medizinische Statistik Saarbrücken, GbR

Saarbrücken, 66113, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Imatinib Mesylate; nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Nikolas von Bubnoff, Professor

  University Hospital Freiburg

  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: Mr.

Study Record Dates

• First Submitted: June 24, 2014
• First Posted: June 25, 2014
• Study Start: March 1, 2014
• Primary Completion: December 1, 2018
• Study Completion: October 1, 2019
• Last Updated: December 2, 2019

Record last verified: 2019-11

Locations

DE (18)