Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS

• ClinicalTrials.gov Identifier: NCT03066648
• Recruitment Status: Recruiting
• First Posted: February 28, 2017
• Last Update Posted: March 11, 2021
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Tracking Information

• First Submitted Date: February 18, 2017
• First Posted Date: February 28, 2017
• Last Update Posted Date: March 11, 2021
• Actual Study Start Date: July 6, 2017
• Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 18, 2018)

• 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

Original Primary Outcome Measures (submitted: February 23, 2017)

• Safety of PDR001 and/or MBG453 in combination with decitabine [ Time Frame: 24 months ]
  Incidence and severity of AEs and SAEs
• Tolerability of PDR001 and/or MBG453 in combination with decitabine [ Time Frame: 24 months ]
  Number of dose interruptions or dose changes
• Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: 2 months ]
  The incidence of DLTs during the first two cycles of treatment with decitabine in combination with PDR001 or MBG453 or combined PDR001 and MBG453.

Current Secondary Outcome Measures (submitted: February 23, 2017)

• 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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS
• 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
• Brief Summary: To characterize the safety and tolerability of 1) MBG453 as a single agent or in combination with PDR001 or 2) PDR001 and/or MBG453 in combination with decitabine in AML and high risk MDS patients, and to identify recommended doses for future studies.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

The study is comprised of five combination arms:

• Evaluation of a fixed dose of the standard of care agent decitabine, in combination with fixed dose PDR001 (Arm 1)
• Evaluation of a fixed dose of the standard of care agent decitabine in combination with escalating dose MBG453 (Arm 2)
• Evaluation of a fixed dose of the standard of care agent decitabine in combination with fixed dose of PDR001 and escalating dose of MBG453 (Arm 3) *
• Evaluation of an escalating dose of MBG453

• Evaluation of a fixed dose of PDR001 in combination with an escalating dose of MBG453

  • The evaluation of decitabine with the combination of PDR001 and MBG453 (Arm 3) will start after Novartis and Investigator's review of the available safety and tolerability data from each of the first two cohorts in Arm 1 and Arm 2.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndromes
• Preleukemia
• Bone Marrow Diseases
• Hematologic Diseases

Intervention

• 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).

Study Arms

• Experimental: Decitabine and PDR001
  Decitabine in combination with PDR001
  Interventions:

  • Drug: Decitabine
  • Drug: PDR001
• Experimental: Decitabine and MBG453
  Decitabine in combination with MBG453
  Interventions:

  • Drug: Decitabine
  • Drug: MBG453
• Experimental: Decitabine, PDR001 and MBG453
  Decitabine in combination with PDR001 and MBG453
  Interventions:

  • Drug: Decitabine
  • Drug: PDR001
  • Drug: MBG453
• Experimental: MBG453
  MBG453 alone
  Intervention: Drug: MBG453
• Experimental: MBG453 and PDR001
  MBG453 in combination with PDR001
  Interventions:

  • Drug: PDR001
  • Drug: MBG453

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 16, 2019): 235
• Original Estimated Enrollment (submitted: February 23, 2017): 70
• Estimated Study Completion Date: November 1, 2021
• Estimated Primary Completion Date: November 1, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

1. Written informed consent must be obtained prior to any screening procedures

2. 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.)
3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. 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.
5. Arms 1-3: Patients must be fit for standard treatment with decitabine as determined by the investigator and as per local decitabine package insert.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Novartis Pharmaceuticals; 1-888-669-6682; Novartis.email@novartis.com

Contact: Novartis Pharmaceuticals; +41613241111

• Listed Location Countries: Australia, Finland, France, Germany, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03066648
• Other Study ID Numbers: CPDR001X2105
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• Study Sponsor: Novartis Pharmaceuticals
• Collaborators: Not Provided

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

• PRS Account: Novartis
• Verification Date: March 2021