A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy

Sponsor
Celgene (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02677922
Collaborator
(none)
131
73
3
79
1.8
0

Study Details

Study Description

Brief Summary

The purpose of this study are

  1. to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and,

  2. to investigate the safety, tolerability, and efficacy of the combinations of AG-120 with azacitidine and AG-221 with azacitidine versus with azacitidine alone in participants with acute myeloid leukemia (AML) with the isocitrate dehydrogenase (IDH) enzyme isoforms 1 or 2 mutations, respectively.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
131 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b/2 Open-Label, Randomized Study of 2 Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine: Oral AG-120 Plus Subcutaneous Azacitidine and Oral AG-221 Plus SC Azacitidine in Subjects With Newly Diagnosed Acute Myeloid Leukemia Harboring an IDH1 or an IDH2 Mutation, Respectively, Who Are Not Candidates to Receive Intensive Induction Chemotherapy
Actual Study Start Date :
Jun 3, 2016
Actual Primary Completion Date :
Aug 2, 2018
Anticipated Study Completion Date :
Jan 4, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: AG-120 + Azacitidine

Drug: AG-120
Specified dose on specified days

Drug: Azacitidine
Specified dose on specified days

Experimental: AG-221 + Azacitidine

Drug: Azacitidine
Specified dose on specified days

Drug: AG-221
Specified dose on specified days

Experimental: Azacitidine

Drug: Azacitidine
Specified dose on specified days

Outcome Measures

Primary Outcome Measures

  1. Dose limiting toxicities (DLTs) [Up to approximately 8 months]

  2. Incidence of adverse events (AEs) [Up to approximately 8 years]

  3. Pharmacokinetics - Maximum observed plasma concentration (Cmax) [Up to approximately 8 months]

  4. Pharmacokinetics - Time to maximum concentration (Tmax) [Up to approximately 8 months]

  5. Pharmacokinetics - Area under the plasma concentration time curve (AUC) [Up to approximately 8 months]

  6. Overall response rate (ORR) as assessed by the investigator [Up to approximately 30 months]

Secondary Outcome Measures

  1. ORR as assessed by the investigator [Up to approximately 13 months]

  2. Sponsor derived morphologic complete remission (CR) [Up to approximately 13 months]

  3. Sponsor derived morphologic complete remission with partial hematologic recovery (CRh) [Up to approximately 13 months]

  4. Event-Free Survival [Up to approximately 30 months]

  5. Incidence of AEs [Up to approximately 8 years]

  6. Complete remission rate [Up to approximately 30 months]

  7. Hematologic improvement rate [Up to approximately 30 months]

  8. Duration of Response according to modified International Working Group (IWG) acute myeloid leukemia (AML) response criteria [Up to approximately 30 months]

  9. Time to response according to modified IWG AML response criteria [Up to approximately 30 months]

  10. Time to sponsored assessed CR [Up to approximately 30 months]

  11. Time to sponsored assessed CRh [Up to approximately 30 months]

  12. Duration of sponsor assessed CR [Up to approximately 30 months]

  13. Duration of sponsor assessed CRh [Up to approximately 30 months]

  14. Overall Survival [Up to approximately 30 months]

  15. One-year survival [Up to approximately 12 months]

  16. Pharmacokinetics - Cmax [Up to approximately 30 months]

  17. Pharmacokinetics - Tmax [Up to approximately 30 months]

  18. Pharmacokinetics - AUC [Up to approximately 30 months]

  19. Change from baseline in European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) [Up to approximately 30 months]

  20. Change from baseline in Health Questionnaire (EQ-5D-5L) [Up to approximately 30 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Newly diagnosed, primary (ie, de novo) or secondary (progression of Myelodysplastic syndrome [MDS] or myeloproliferative neoplasms [MPN], or therapy-related) acute myeloid leukemia (AML) according to the WHO classification with ≥ 20% leukemic blasts in the bone marrow

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

  • Agree to serial bone marrow aspirate/biopsies

Exclusion Criteria:
  • Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype

  • AML secondary to chronic myelogenous leukemia (CML)

  • Received a targeted agent against an isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation

  • Has or is suspected of having central nervous system (CNS) leukemia. Evaluation of cerebrospinal fluid is only required if CNS involvement by leukemia is suspected during screening

Other protocol defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

Site City State Country Postal Code
1 City of Hope Duarte California United States 91010-301
2 Local Institution - 107 New Haven Connecticut United States 06510
3 Yale Cancer Center New Haven Connecticut United States 06510
4 Northwestern University Chicago Illinois United States 60611
5 University of Chicago Chicago Illinois United States 60637
6 Massachusetts General Hospital Boston Massachusetts United States 02114
7 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02115
8 Dana Farber Cancer Institute Boston Massachusetts United States 02115
9 Memorial Sloan Kettering Cancer Center New York New York United States 10065
10 Sarah Cannon Research Inst Nashville Tennessee United States 37203
11 UT Southwestern Medical Center at Dallas Dallas Texas United States 75390-85520
12 MD Anderson Cancer Center Houston Texas United States 77030
13 Royal Adelaide Hospital Adelaide South Australia Australia SA 5000
14 Parkville Cancer Clinical Trials Unit Melbourne Australia 3000
15 The Alfred Hospital Melbourne Australia 3141
16 Royal Perth Hospital Perth Australia 6000
17 Princess Margaret Hospital, Medical Oncology Toronto Ontario Canada M5G 2M9
18 CHRU de Lille-Hopital Claude Huriez Service des Maladies du Sang Lille France 59037
19 Institut Paoli Calmettes Marseille Cedex 9 France 13273
20 Centre Hospitalier Universitaire de Nantes Nantes France 44093
21 Hopital Saint Louis Paris Cedex 10 France 75475
22 Hospital haut leveque Pessac France 33604
23 Centre Hospitalier Lyon Sud Pierre Benite France 69495
24 Institut Universitaire du Cancer Oncopole Toulouse France 31059
25 CHRU Hopital Bretonneau Tours cedex France 37044
26 Institut Gustave Roussy Villejuif CEDEX France 94805
27 Local Institution - 201 Villejuif CEDEX France 94805
28 Medizinische Klinik III Klinikum der Universität München-Großhadern Berlin Germany 12200
29 Universitaetsklinikum Carl Gustav Carus TU Dresden Dresden Germany 01307
30 Heinrich Heine Universitat Dusseldorf Düsseldorf Germany 40225
31 Universitatsklinikum Frankfurt Frankfurt Germany 60590
32 Zentrum Innere Medizin Klinik fur Hamatologie Hannover Germany 30625
33 Universitatsklinikum Ulm Ulm Germany 89081
34 Azienda Ospedaliero-Universitaria di Bologna - Policlinico S.Orsola-Malpighi Bologna, Emilia-Romagna Italy 40138
35 Azienda Ospedaliero-Universitaria Careggi Firenze Italy 50134
36 Azienda Ospedaliera Universitaria S. Martino di Genova Genova Italy 16132
37 Azienda Ospedaliera San Luigi Gonzaga Orbassano Italy 10043
38 Local Institution - 251 Orbassano Italy 10043
39 Hospital of Di Padova Padova Italy 35128
40 Azienda Ospedaliera Ospedali Riuniti Marche Nord AORMN Pesaro Italy 31122
41 Azienda Ospedaliera S. Andrea - Università La Sapienza Roma Italy 00189
42 Local Institution - 255 Roma Italy 00189
43 Samsung Medical Center Seoul Korea, Republic of 135-710
44 The Catholic University of Korea Seoul - Saint Mary's Hospital Seoul Korea, Republic of 137-701
45 Asan Medical Center Seoul Korea, Republic of 138-736
46 Local Institution - 350 Seoul Korea, Republic of 138-736
47 VU University Medical Center Amsterdam Netherlands
48 Universitair Medisch Centrum Groningen Groningen Netherlands 9713 GZ
49 Erasmus University Medical Center Rotterdam Netherlands 3015 GJ
50 University Medical Center Utrecht Utrecht Netherlands 3584 CX
51 Instituto Portugues de Oncologia de Lisboa Lisboa Portugal 1099-023
52 Centro Hospitalar de Lisboa Central - Hospital de Santo António dos Capuchos Lisboa Portugal 1169-050
53 Instituto Portugues de Oncologia do Porto Porto Portugal 4200-072
54 H Clinic I Provincial Barcelona Spain 08036
55 Hospital de Bellvitge Barcelona Spain 08907
56 Local Institution - 375 Barcelona Spain 08907
57 Hospital Universitario Vall D Hebron Barcelona Spain 8035
58 Hospital General de la Palma Breña Alta Spain 38713
59 Hospital San Pedro de Alcantara Caceres Spain 10005
60 Hospital General Universitario Gregorio Maranon Madrid Spain 28007
61 M. D. Anderson Madrid Spain 28033
62 Hospital General Carlos Haya Malaga Spain 29010
63 Hospital Universitario La Fe Valencia Spain 46009
64 UniversitatsSpital Basel Basel Switzerland 4031
65 Centre Hospitalier Universitaire Vaudois CHUV BH-04 Lausanne Switzerland 1011
66 Universitatsspital Zurich Zurich Switzerland
67 Queen Elizabeth Hospital UHB NHS Foundation Trust Birmingham United Kingdom B15 2TH
68 John Radcliffe Hospital Headington United Kingdom OX3 9DU
69 Local Institution - 427 Headington United Kingdom OX3 9DU
70 Leeds Teaching Hospitals Trust Leeds United Kingdom LS7 4SA
71 Barts Cancer Institute, Queen Mary University of London, Charterhouse Square London United Kingdom EC1M 6BQ
72 King's College Hospital London United Kingdom SE5 9RS
73 Royal Marsden Hospital Sutton (Surrey) United Kingdom SM2 5PT

Sponsors and Collaborators

  • Celgene

Investigators

  • Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Celgene
ClinicalTrials.gov Identifier:
NCT02677922
Other Study ID Numbers:
  • AG-221-AML-005
  • 2015-003951-23
First Posted:
Feb 9, 2016
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022

Study Results

No Results Posted as of Aug 19, 2022