Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS
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ClinicalTrials.gov Identifier: NCT03066648 |
Recruitment Status :
Recruiting
First Posted : February 28, 2017
Last Update Posted : May 13, 2020
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Bone Marrow Diseases Hematologic Diseases | Drug: Decitabine Drug: PDR001 Drug: MBG453 | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 235 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | The study is comprised of five combination arms:
|
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase 1b, Multi-arm, Open-label Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome |
Actual Study Start Date : | July 6, 2017 |
Estimated Primary Completion Date : | November 1, 2021 |
Estimated Study Completion Date : | November 1, 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: Decitabine and PDR001
Decitabine in combination with PDR001
|
Drug: Decitabine
Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.
Other Name: 5-aza-2'-deoxycytidine Drug: PDR001 PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2. |
Experimental: Decitabine and MBG453
Decitabine in combination with MBG453
|
Drug: Decitabine
Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.
Other Name: 5-aza-2'-deoxycytidine Drug: MBG453 MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer). |
Experimental: Decitabine, PDR001 and MBG453
Decitabine in combination with PDR001 and MBG453
|
Drug: Decitabine
Decitabine is a cytidine deoxynucleoside analogue that selectively inhibits DNA methyltransferases at low doses, resulting in gene promoter hypomethylation.
Other Name: 5-aza-2'-deoxycytidine Drug: PDR001 PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2. Drug: MBG453 MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer). |
Experimental: MBG453
MBG453 alone
|
Drug: MBG453
MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer). |
Experimental: MBG453 and PDR001
MBG453 in combination with PDR001
|
Drug: PDR001
PDR001 is a high-affinity, ligand-blocking, humanized IgG4 monoclonal antibody directed against PD-1 that blocks the binding of PD-L1 and PD-L2. Drug: MBG453 MBG453 is a high-affinity, humanized anti-TIM-3 IgG4 monoclonal antibody which blocks the binding of TIM-3 to phosphatidylserine (PtdSer). |
- Safety of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine. [ Time Frame: 24 months ]Incidence and severity of AEs and SAEs
- Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 2 months ]The incidence of DLTs during the first two cycles of treatment with MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine.
- Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 1 month ]The incidence of DLTs during the first cycle of treatment with MBG453.
- Tolerability of MBG453 single agent treatment or MBG453 in combination with PDR001 or PDR001 and/or MBG453 in combination with decitabine. [ Time Frame: 24 months ]Incidence and severity of AEs and SAEs
- AUC of PDR001, MBG453 and decitabine. [ Time Frame: 24 months ]AUC
- Cmax of PDR001, MBG453 and decitabine [ Time Frame: 24 months ]Cmax
- Tmax of PDR001, MBG453 and decitabine [ Time Frame: 24 months ]Tmax
- Half-life of PDR001, MBG453 and decitabine [ Time Frame: 24 months ]Half-life
- Concentration vs time profile of PDR001, MBG453 and decitabine [ Time Frame: 24 months ]Concentration vs. time
- Overall Response Rate (ORR) [ Time Frame: 24 months ]Determine ORR in each arm of the study
- Best Overall Response (BOR) [ Time Frame: 24 months ]Determine BOR in each arm of the study
- Progression Free Survival (PFS) [ Time Frame: 24 months ]Determine PFS in each arm of the study
- Time to Progression (TTP) [ Time Frame: 24 months ]Determine TTP in each arm of the study
- Duration of Response (DOR) [ Time Frame: 24 months ]Determine DOR in each arm of the study

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
- Written informed consent must be obtained prior to any screening procedures
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Male or female patients ≥ 18 years of age who present with one of the following:
Arms 1-3:
- Refractory/relapsed AML following ≥1 prior therapies and are deemed by the investigator not to be candidates for standard therapy, including re-induction with cytarabine or other established chemotherapy regimens for patients with AML (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
- De novo AML patients who are suitable for treatment with decitabine (patients who are suitable for standard induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
- High risk MDS (patients who are suitable for standard re-induction chemotherapy or hematopoietic stem cell transplantation and willing to receive it are excluded)
Arms 4-5:
- Refractory / relapsed AML following ≥1 prior therapies (Arms 4a & 5a)
- High risk MDS who have failed hypomethylating agent therapy (Arms 4b & 5b) (Note: hypomethylating agent failure is defined as progressive disease on hypomethylating agent therapy or lack of clinically meaningful response as deemed by investigator after at least 4 cycles of hypomethylating agent therapy.)
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and be willing to undergo a bone marrow aspirate and/biopsy at screening, during and at the end of therapy on this study. Exceptions may be considered after documented discussion with Novartis.
- Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by the investigator and as per local decitabine package insert.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03066648
Contact: Novartis Pharmaceuticals | 1-888-669-6682 | Novartis.email@novartis.com | |
Contact: Novartis Pharmaceuticals | +41613241111 |
United States, Massachusetts | |
Massachusetts General Hospital | Recruiting |
Boston, Massachusetts, United States, 02114 | |
Contact: Meghan Burke 617-726-5131 Mburke19@partners.org | |
Principal Investigator: Andrew M. Brunner | |
United States, Oregon | |
Oregon Health and Science University | Recruiting |
Portland, Oregon, United States, 97239 | |
Contact: Michael Lue 503-418-2294 luem@ohsu.edu | |
Principal Investigator: Uma Borate | |
United States, Texas | |
MD Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Maria Faccolli 713-792-2279 mafacciolli@mdanderson.org | |
Principal Investigator: Guillermo Garcia-Manero | |
Australia, Victoria | |
Novartis Investigative Site | Recruiting |
Melbourne, Victoria, Australia, 3004 | |
Finland | |
Novartis Investigative Site | Recruiting |
Helsinki, Finland, FIN 00290 | |
France | |
Novartis Investigative Site | Recruiting |
Marseille, France, 13273 | |
Germany | |
Novartis Investigative Site | Recruiting |
Dresden, Germany, 01307 | |
Novartis Investigative Site | Recruiting |
Jena, Germany, 07740 | |
Netherlands | |
Novartis Investigative Site | Recruiting |
Amsterdam, Netherlands, 1081 HV | |
Spain | |
Novartis Investigative Site | Recruiting |
Barcelona, Catalunya, Spain, 08036 | |
United Kingdom | |
Novartis Investigative Site | Recruiting |
Cardiff, United Kingdom, CF4 4XN |
Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03066648 |
Other Study ID Numbers: |
CPDR001X2105 |
First Posted: | February 28, 2017 Key Record Dates |
Last Update Posted: | May 13, 2020 |
Last Verified: | May 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Acute Myeloid Leukemia Myelodysplastic syndromes |
Leukemia Preleukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Hematologic Diseases Bone Marrow Diseases Syndrome Disease Pathologic Processes |
Neoplasms by Histologic Type Neoplasms Precancerous Conditions Decitabine Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Enzyme Inhibitors |