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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 : March 11, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE February 18, 2017
First Posted Date  ICMJE February 28, 2017
Last Update Posted Date March 11, 2021
Actual Study Start Date  ICMJE July 6, 2017
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of PDR001 and/or MBG453 in Combination With Decitabine in Patients With AML or High Risk MDS
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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  ICMJE
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • Myelodysplastic Syndromes
  • Preleukemia
  • Bone Marrow Diseases
  • Hematologic Diseases
Intervention  ICMJE
  • 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  ICMJE
  • 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 16, 2019)
235
Original Estimated Enrollment  ICMJE
 (submitted: February 23, 2017)
70
Estimated Study Completion Date  ICMJE November 1, 2021
Estimated Primary Completion Date November 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Novartis Pharmaceuticals 1-888-669-6682 Novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111
Listed Location Countries  ICMJE Australia,   Finland,   France,   Germany,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03066648
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP