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

NCT02545283 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: WO295192014-003065-15
• Study Type: interventional
• Target: 447
• Locations: 18 countries
• Sites: 81

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival in TP53 WT Population

  P53 tumor protein Wild Type (TP53 WT) population's Overall Survival was compared in participants with relapsed or refractory (R/R) acute myeloid leukemia (AML) who had been randomized to idasanutlin in combination with cytarabine versus those who had been randomized to cytarabine and placebo. The study was terminated because of futility, therefore did not reach the planned end of the study.

  From randomization to death from any cause (up to approximately 4.5 years)

Secondary Outcomes (34)

• Percentage of Participants in Complete Response (CR) at the End of Induction According to Hematologic Malignancy Response Assessment (HMRA) in TP53 WT Population

  At the end of induction (up to Day 56)

• Event-Free Survival (EFS) According to HMRA in TP53 WT Population

  From randomization up to treatment failure, relapse, or death from any cause (up to approximately 4.5 years)

• Percentage of Participants With Overall Remission (CR, CRp, and CRi) at the End of Induction According to HMRA in TP53 WT Population

  At the end of induction (up to Day 56)

• Duration of Remission Following CR (DOR) in TP53 WT Population

  From achieving CR until relapse or death from any cause (up to approximately 4.5 years)

• Percentage of Participants Undergoing HSCT Following Complete Response (CR), in TP53 WT Population

  Baseline up to approximately 4.5 years

Study Arms (2)

Idasanutlin plus Cytarabine

EXPERIMENTAL

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.

Drug: Cytarabine; Drug: Idasanutlin

Placebo plus Cytarabine

PLACEBO COMPARATOR

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.

Drug: Cytarabine; Other: Placebo

Interventions

Cytarabine DRUG

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

Idasanutlin plus Cytarabine; Placebo plus Cytarabine

Idasanutlin 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.

Also known as: RG7388

Idasanutlin plus Cytarabine

Placebo OTHER

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

Placebo plus Cytarabine

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (82)

Northwell Health

Great Neck, New York, 11021, United States

Location

New York Medical College

Hawthorne, New York, 10532, United States

Location

Ichan School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Abramson Cancer Center; Univ of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Baylor University Medical Center

Dallas, Texas, 75204, United States

Location

M.D. Anderson Cancer Center; Department of Hematology

Houston, Texas, 77030, United States

Location

Canberra Hospital; Haematology Department

Canberra, Australian Capital Territory, 2605, Australia

Location

Concord Repatriation General Hospital; Haematology

Sydney, New South Wales, 2139, Australia

Location

Royal Adelaide Hospital; Haematology Clinical Trials

Adelaide, South Australia, 5000, Australia

Location

Geelong Hospital; Andrew Love Cancer Centre

Geelong, Victoria, 3220, Australia

Location

Alfred Hospital; Clinical Haematology and Bone Marrow Transplantation

Melbourne, Victoria, 3004, Australia

Location

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

Graz, 8036, Austria

Location

CH Jolimont - Lobbes (Jolimont)

Haine-Saint-Paul, 7100, Belgium

Location

CHU Sart-Tilman

Liège, 4000, Belgium

Location

AZ Delta (Campus Rumbeke)

Roeselare, 8800, Belgium

Location

Juravinski Cancer Clinic; Clinical Trials Department

Hamilton, Ontario, L8V 5C2, Canada

Location

Helsinki University Central Hospital; Hematology

Helsinki, 00290, Finland

Location

Tampere University Hospital; Hematology

Tampere, 33521, Finland

Location

Centre Hospitalier Uni Ire; Service Des Maladies Du Sang

Angers, 49933, France

Location

Hopital Claude Huriez; Hematologie

Lille, 59037, France

Location

Institut J Paoli I Calmettes; Onco Hematologie 2

Marseille, 13273, France

Location

Hopital Hotel Dieu Et Hme;Hopital De Jour

Nantes, 44093, France

Location

Hopital Saint Louis; Oncologie Medicale

Paris, 75475, France

Location

HOPITAL SAINT ANTOINE;Hematologie Clinique

Paris, 75571, France

Location

Hopital De Haut Leveque; Hematologie Clinique

Pessac, 33604, France

Location

Centre Hospitalier Lyon Sud; Hematolgie

Pierre-Bénite, 69495, France

Location

IUCT Oncopole; Hematologie

Toulouse, 31059, France

Location

Hopitaux De Brabois; Hematologie Medecine Interne

Vandœuvre-lès-Nancy, 54511, France

Location

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

Aachen, 52074, Germany

Location

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

Bonn, 53127, Germany

Location

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

Braunschweig, 38114, Germany

Location

Klinikum Chemnitz gGmbH Krankenhaus Küchwald Klinik f.Innere Medizin III

Chemnitz, 09113, Germany

Location

Klinik der Uni zu Köln; I. Med. Klinik

Cologne, 50937, Germany

Location

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

Dresden, 01307, Germany

Location

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

Hanover, 30625, Germany

Location

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

Mainz, 55131, Germany

Location

Universitätsklinikum Marburg Zentrum f. Innere Medizin

Marburg, 35043, Germany

Location

Shaare Zedek Medical Center; Hematology Dept.

Jerusalem, 9103102, Israel

Location

Hadassah Ein Karem Hospital; Haematology

Jerusalem, 9112001, Israel

Location

Rabin Medical Center-Beilinson Campus;Hematology-Oncology

Petah Tikva, 4941492, Israel

Location

Ichilov Sourasky Medical Center; Heamatology

Tel Aviv, 6423906, Israel

Location

Ospedale Cardarelli; Divisione Di Ematologia

Napoli, Campania, 80131, Italy

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

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

Meldola, Emilia-Romagna, 47014, Italy

Location

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

Ravenna, Emilia-Romagna, 48100, Italy

Location

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

Udine, Friuli Venezia Giulia, 33100, Italy

Location

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

Rome, Lazio, 00133, Italy

Location

IRCCS AOU S.Martino; Clinica Ematologica

Genoa, Liguria, 16132, Italy

Location

ASST PAPA GIOVANNI XXIII; Ematologia

Bergamo, Lombardy, 24127, Italy

Location

Ospedale San Raffaele, IRCCS

Milan, Lombardy, 20132, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, 20162, Italy

Location

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

Orbassano (TO), Piedmont, 10043, Italy

Location

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

Turin, Piedmont, 10126, Italy

Location

Az. Osp. Di Careggi; Divisione Di Ematologia

Florence, Tuscany, 50135, Italy

Location

Ospedale Santa Chiara; Unita Operativa Di Ematologia

Pisa, Tuscany, 56100, Italy

Location

Academisch Medisch Centrum; Hematologie

Amsterdam, 1105 AZ, Netherlands

Location

Academisch Ziekenhuis Maastricht

Maastricht, 6202 AZ, Netherlands

Location

Auckland city hospital; Auckland Regional Cancer Centre and Blood Service

Auckland, 1023, New Zealand

Location

Haukeland Universitetssjukehus; Klinisk forskningspost

Bergen, 5021, Norway

Location

Oslo Universitetssykehus HF, Rikshospitalet

Oslo, 0372, Norway

Location

Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología

Panama City, 0824, Panama

Location

"Hematological Scientific Center

Moscow, 125167, Russia

Location

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

Saint Petersburg, 197022, Russia

Location

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

Saint Petersburg, 197341, Russia

Location

Pusan National University Hospital

Busan, 49241, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Seoul St Mary's Hospital

Seoul, 06591, South Korea

Location

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

Barcelona, 08025, Spain

Location

Hospital Clínic i Provincial; Servicio de Hematología y Oncología

Barcelona, 08036, Spain

Location

Hospital Univ. 12 de Octubre; Servicio de Hematologia

Madrid, 28041, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Universitario la Fe; Servicio de Hematologia

Valencia, 46026, Spain

Location

Universitätsspital Basel; Hämatologie

Basel, 4031, Switzerland

Location

Universitätsspital Zürich Medizin Hämatologie; Klinik für Hämatologie

Zurich, 8091, Switzerland

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

St Bartholomew's Hospital

London, EC1M 6BQ, United Kingdom

Location

Christie Hospital NHS Trust

Manchester, M20 4BX, United Kingdom

Location

Royal Marsden NHS Foundation Trust

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 32167393 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cytarabine; RG7388

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Reference Study ID Number: WO29519
• Organization: www.roche.com/about_roche/roche_worldwide.htm

global-roche-genentech-trials@gene.com

888-662-6728 (U.S. Only)

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 9, 2015
• Study Start: December 30, 2015
• Primary Completion: April 24, 2020
• Study Completion: April 24, 2020
• Last Updated: January 11, 2022
• Results First Posted: September 14, 2021

Record last verified: 2021-12

Locations

CH (2); IT (14); ES (5); GB (5); AU (5); NZ (1); PA (1); FR (10); US (7); DE (9); BE (3); CA (1); KR (5); FI (2); IL (4); NL (2); NO (2); RU (3)