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
Study Details
Study Description
Brief Summary
The purpose of this study are
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to determine the recommended combination dose of AG-120 and AG-221 separately when administered with azacitidine and,
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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
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
- Dose limiting toxicities (DLTs) [Up to approximately 8 months]
- Incidence of adverse events (AEs) [Up to approximately 8 years]
- Pharmacokinetics - Maximum observed plasma concentration (Cmax) [Up to approximately 8 months]
- Pharmacokinetics - Time to maximum concentration (Tmax) [Up to approximately 8 months]
- Pharmacokinetics - Area under the plasma concentration time curve (AUC) [Up to approximately 8 months]
- Overall response rate (ORR) as assessed by the investigator [Up to approximately 30 months]
Secondary Outcome Measures
- ORR as assessed by the investigator [Up to approximately 13 months]
- Sponsor derived morphologic complete remission (CR) [Up to approximately 13 months]
- Sponsor derived morphologic complete remission with partial hematologic recovery (CRh) [Up to approximately 13 months]
- Event-Free Survival [Up to approximately 30 months]
- Incidence of AEs [Up to approximately 8 years]
- Complete remission rate [Up to approximately 30 months]
- Hematologic improvement rate [Up to approximately 30 months]
- Duration of Response according to modified International Working Group (IWG) acute myeloid leukemia (AML) response criteria [Up to approximately 30 months]
- Time to response according to modified IWG AML response criteria [Up to approximately 30 months]
- Time to sponsored assessed CR [Up to approximately 30 months]
- Time to sponsored assessed CRh [Up to approximately 30 months]
- Duration of sponsor assessed CR [Up to approximately 30 months]
- Duration of sponsor assessed CRh [Up to approximately 30 months]
- Overall Survival [Up to approximately 30 months]
- One-year survival [Up to approximately 12 months]
- Pharmacokinetics - Cmax [Up to approximately 30 months]
- Pharmacokinetics - Tmax [Up to approximately 30 months]
- Pharmacokinetics - AUC [Up to approximately 30 months]
- Change from baseline in European Organization for Research and Treatment of Cancer Quality-of-Life questionnaire (EORTC QLQ-C30) [Up to approximately 30 months]
- Change from baseline in Health Questionnaire (EQ-5D-5L) [Up to approximately 30 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
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Agree to serial bone marrow aspirate/biopsies
Exclusion Criteria:
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Suspected or proven to have acute promyelocytic leukemia based on morphology, immunophenotype, molecular assay, or karyotype
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AML secondary to chronic myelogenous leukemia (CML)
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Received a targeted agent against an isocitrate dehydrogenase 1 (IDH1) or isocitrate dehydrogenase 2 (IDH2) mutation
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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.- AG-221-AML-005
- 2015-003951-23