A Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML)

NCT ID: NCT02545283

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 447 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-30
• Study Completion Date: 2020-04-24

Brief Summary

This is a multicenter, double-blind, randomized, placebo-controlled study designed to compare overall survival in participants with relapsed or refractory AML treated with idasanutlin in combination with cytarabine versus participants treated with placebo and cytarabine. Participants will receive induction treatment with idasanutlin/placebo and cytarabine (Cycle 1). Responding participants may continue to receive a maximum of further two cycles of consolidation (Cycle 2 and Cycle 3). Complete remission (CR), CR with incomplete platelet count recovery (CRp), overall remission rate (ORR), event-free survival (EFS) and percentage of participants with an allogeneic hematopoietic stem cell transplant (HSCT) will also be compared between treatment arms. This study will include participants with and without TP53 wild type (TP53 WT) mutations.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Idasanutlin plus Cytarabine

Participants will receive induction therapy idasanutlin and cytarabine for 5 Days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or complete remission with incomplete blood count recovery (CRi), up to 28 additional days are allowed for blood count recovery, if needed.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Participants will receive cytarabine 1 gram per square meter (g/m\^2) intravenous (IV) infusion for 5 days of every treatment cycle.

Idasanutlin

Intervention Type: DRUG

Participants will receive idasanutlin 300 mg per oral (PO) twice daily (BID) (in Cycle 1) or once daily (QD) (in Cycles 2 and 3) for 5 days of every treatment cycle.

Placebo plus Cytarabine

Participants will receive induction therapy idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in Cycle 1 (treatment cycle length=28 days). Responding participants may continue with consolidation therapy for a maximum of 2 additional cycles including idasanutlin matching placebo and cytarabine for 5 days followed by 23 days of rest in each cycle (treatment cycle length=28 days). After each cycle, for participants achieving CRp or CRi, up to 28 additional days are allowed for blood count recovery, if needed.

Group Type: PLACEBO_COMPARATOR

Cytarabine

Intervention Type: DRUG

Participants will receive cytarabine 1 gram per square meter (g/m\^2) intravenous (IV) infusion for 5 days of every treatment cycle.

Placebo

Intervention Type: OTHER

Participants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle.

Interventions

Cytarabine

Participants will receive cytarabine 1 gram per square meter (g/m\^2) intravenous (IV) infusion for 5 days of every treatment cycle.

Intervention Type: DRUG

Idasanutlin

Participants will receive idasanutlin 300 mg per oral (PO) twice daily (BID) (in Cycle 1) or once daily (QD) (in Cycles 2 and 3) for 5 days of every treatment cycle.

Intervention Type: DRUG

Placebo

Participants will receive idasanutlin matching placebo PO BID or QD for 5 days of every treatment cycle.

Intervention Type: OTHER

Other Intervention Names

RG7388

Eligibility Criteria

Inclusion Criteria

• Documented/confirmed first/second refractory/relapsed AML using World Health Organization classification, except acute promyelocytic leukemia
• No more than 2 prior induction regimens (excluding prior HSCT) in their first line treatment and one must have included cytarabine with an anthracycline (or anthracenedione)
• Eastern Cooperative Oncology Group performance status of 0 to 2
• Adequate hepatic and renal function
• White blood cell (WBC) count at randomization less than or equal to (</=) 50000 cells per cubic millimeter (/mm^3)

Exclusion Criteria

• First relapsed participants aged less than (<) 60 years with first CR duration greater than (>) 1 year
• Participants with prior documented antecedent hematological disorder (AHD)
• AML secondary to any prior chemotherapy unrelated to leukemia
• Participants who are either refractory to or relapsed within 90 days of receiving a regimen containing a cumulative dose of greater than or equal to (>/=) 18 g/m^2 of cytarabine
• Participants who have received allogeneic HSCT within 90 days prior to randomization
• Participants who have received immunosuppressive therapy for graft versus host disease or for engraftment syndrome after autologous stem cell transplantation within 2 weeks prior to randomization
• Prior treatment with an Murine Double Minute 2 (MDM2) antagonist
• Participants receiving any other investigational or commercial agents or therapies administered with the intention to treat their malignancy within 30 days from first receipt of study drug
• Participants with a history of other malignancy within 5 years prior to screening except for malignancy that has been in remission without treatment for at least 2 years prior to randomization
• Participants who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study
• Participants with extramedullary AML with no evidence of systemic involvement
• Pregnant or breastfeeding participants

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Northwell Health

Great Neck, New York, United States

New York Medical College

Hawthorne, New York, United States

Ichan School of Medicine at Mount Sinai

New York, New York, United States

Abramson Cancer Center; Univ of Pennsylvania

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Baylor University Medical Center

Dallas, Texas, United States

M.D. Anderson Cancer Center; Department of Hematology

Houston, Texas, United States

Canberra Hospital; Haematology Department

Canberra, Australian Capital Territory, Australia

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, Australia

Royal Adelaide Hospital; Haematology Clinical Trials

Adelaide, South Australia, Australia

Geelong Hospital; Andrew Love Cancer Centre

Geelong, Victoria, Australia

Alfred Hospital; Clinical Haematology and Bone Marrow Transplantation

Melbourne, Victoria, Australia

Lkh-Univ. Klinikum Graz; Klin. Abt. Für Hämatologie

Graz, , Austria

CH Jolimont - Lobbes (Jolimont)

Haine-Saint-Paul, , Belgium

CHU Sart-Tilman

Liège, , Belgium

AZ Delta (Campus Rumbeke)

Roeselare, , Belgium

Juravinski Cancer Clinic; Clinical Trials Department

Hamilton, Ontario, Canada

Helsinki University Central Hospital; Hematology

Helsinki, , Finland

Tampere University Hospital; Hematology

Tampere, , Finland

Centre Hospitalier Uni Ire; Service Des Maladies Du Sang

Angers, , France

Hopital Claude Huriez; Hematologie

Lille, , France

Institut J Paoli I Calmettes; Onco Hematologie 2

Marseille, , France

Hopital Hotel Dieu Et Hme;Hopital De Jour

Nantes, , France

Hopital Saint Louis; Oncologie Medicale

Paris, , France

HOPITAL SAINT ANTOINE;Hematologie Clinique

Paris, , France

Hopital De Haut Leveque; Hematologie Clinique

Pessac, , France

Centre Hospitalier Lyon Sud; Hematolgie

Pierre-Bénite, , France

IUCT Oncopole; Hematologie

Toulouse, , France

Hopitaux De Brabois; Hematologie Medecine Interne

Vandœuvre-lès-Nancy, , France

Uniklinik RWTH Aachen; Klinik IV; Klinik Hämatologie, Onkologie, Hämostaseologie und Stamm.

Aachen, , Germany

Universitätsklinikum Bonn; Med. Klinik und Poliklinik III; Hämatologie, Onkologie und Rheumatologie

Bonn, , Germany

Klinikum Braunschweig; Medizinische Klinik III; Klinik für Hämatologie und Onkologie

Braunschweig, , Germany

Klinikum Chemnitz gGmbH Krankenhaus Küchwald Klinik f.Innere Medizin III

Chemnitz, , Germany

Klinik der Uni zu Köln; I. Med. Klinik

Cologne, , Germany

Universitätsklinikum "Carl Gustav Carus"; Medizinische Klinik und Poliklinik I

Dresden, , Germany

Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie

Hanover, , Germany

Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik

Mainz, , Germany

Universitätsklinikum Marburg Zentrum f. Innere Medizin

Marburg, , Germany

Shaare Zedek Medical Center; Hematology Dept.

Jerusalem, , Israel

Hadassah Ein Karem Hospital; Haematology

Jerusalem, , Israel

Rabin Medical Center-Beilinson Campus;Hematology-Oncology

Petah Tikva, , Israel

Ichilov Sourasky Medical Center; Heamatology

Tel Aviv, , Israel

Ospedale Cardarelli; Divisione Di Ematologia

Napoli, Campania, Italy

Az. Osp. S. Orsola Malpighi; Istituto Di Oncologia Seragnoli

Bologna, Emilia-Romagna, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST); Onco-Ematologia

Meldola, Emilia-Romagna, Italy

Az. Osp. S. Maria Delle Croci; U.O. Di Ematologia

Ravenna, Emilia-Romagna, Italy

A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia; Clinica Ematologica

Udine, Friuli Venezia Giulia, Italy

Az. Osp. Uni Ria Policlinico Tor Vergata; Unita Di Ematologia

Rome, Lazio, Italy

IRCCS AOU S.Martino; Clinica Ematologica

Genoa, Liguria, Italy

ASST PAPA GIOVANNI XXIII; Ematologia

Bergamo, Lombardy, Italy

Ospedale San Raffaele, IRCCS

Milan, Lombardy, Italy

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, Italy

A.O. Universitaria San Luigi Gonzaga di Orbassano; Ambulatorio per le Malattie Rare del Polmone

Orbassano (TO), Piedmont, Italy

A.O.U. Citta' Della Salute E Della Scienza-P.O. Molinette;S.C. Ematologia

Turin, Piedmont, Italy

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, Italy

Ospedale Santa Chiara; Unita Operativa Di Ematologia

Pisa, Tuscany, Italy

Academisch Medisch Centrum; Hematologie

Amsterdam, , Netherlands

Academisch Ziekenhuis Maastricht

Maastricht, , Netherlands

Auckland city hospital; Auckland Regional Cancer Centre and Blood Service

Auckland, , New Zealand

Haukeland Universitetssjukehus; Klinisk forskningspost

Bergen, , Norway

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, , Norway

Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología

Panama City, , Panama

"Hematological Scientific Center

Moscow, , Russia

St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

Saint Petersburg, , Russia

FGBU "Federal Medical and Research Center named after V.A.Almazov" Russian Ministry of Health

Saint Petersburg, , Russia

Pusan National University Hospital

Busan, , South Korea

Chonnam National University Hwasun Hospital

Jeollanam-do, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul St Mary's Hospital

Seoul, , South Korea

Hospital de la Santa Creu i Sant Pau; Servicio de Hematologia

Barcelona, , Spain

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, , Spain

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitario la Fe; Servicio de Hematologia

Valencia, , Spain

Universitätsspital Basel; Hämatologie

Basel, , Switzerland

Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie

Zurich, , Switzerland

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

University Hospital of Wales

Cardiff, , United Kingdom

St Bartholomew's Hospital

London, , United Kingdom

Christie Hospital NHS Trust

Manchester, , United Kingdom

Royal Marsden NHS Foundation Trust

Sutton, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Canada; Finland; France; Germany; Israel; Italy; Netherlands; New Zealand; Norway; Panama; Russia; South Korea; Spain; Switzerland; United Kingdom

References

Montesinos P, Beckermann BM, Catalani O, Esteve J, Gamel K, Konopleva MY, Martinelli G, Monnet A, Papayannidis C, Park A, Recher C, Rodriguez-Veiga R, Rollig C, Vey N, Wei AH, Yoon SS, Fenaux P. MIRROS: a randomized, placebo-controlled, Phase III trial of cytarabine +/- idasanutlin in relapsed or refractory acute myeloid leukemia. Future Oncol. 2020 May;16(13):807-815. doi: 10.2217/fon-2020-0044. Epub 2020 Mar 13.

Reference Type: DERIVED

PMID: 32167393 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-003065-15

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO29519

Identifier Type: -

Identifier Source: org_study_id