Clinical Trials /

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

NCT03066648

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: CPDR001X2105
  • NCT ID: NCT03066648

Conditions

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

Interventions

DrugSynonymsArms
Decitabine5-aza-2'-deoxycytidineDecitabine and PDR001
PDR001Decitabine and PDR001
MBG453Decitabine and MBG453

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Decitabine and PDR001ExperimentalDecitabine in combination with PDR001
  • Decitabine
  • PDR001
Decitabine and MBG453ExperimentalDecitabine in combination with MBG453
  • Decitabine
  • MBG453
Decitabine, PDR001 and MBG453ExperimentalDecitabine in combination with PDR001 and MBG453
  • Decitabine
  • PDR001
  • MBG453
MBG453ExperimentalMBG453 alone
  • MBG453
MBG453 and PDR001ExperimentalMBG453 in combination with PDR001
  • PDR001
  • MBG453

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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Incidence and severity of AEs and SAEs

Secondary Outcome Measures

Measure:AUC of PDR001, MBG453 and decitabine.
Time Frame:24 months
Safety Issue:
Description:AUC
Measure:Cmax of PDR001, MBG453 and decitabine
Time Frame:24 months
Safety Issue:
Description:Cmax
Measure:Tmax of PDR001, MBG453 and decitabine
Time Frame:24 months
Safety Issue:
Description:Tmax
Measure:Half-life of PDR001, MBG453 and decitabine
Time Frame:24 months
Safety Issue:
Description:Half-life
Measure:Concentration vs time profile of PDR001, MBG453 and decitabine
Time Frame:24 months
Safety Issue:
Description:Concentration vs. time
Measure:Overall Response Rate (ORR)
Time Frame:24 months
Safety Issue:
Description:Determine ORR in each arm of the study
Measure:Best Overall Response (BOR)
Time Frame:24 months
Safety Issue:
Description:Determine BOR in each arm of the study
Measure:Progression Free Survival (PFS)
Time Frame:24 months
Safety Issue:
Description:Determine PFS in each arm of the study
Measure:Time to Progression (TTP)
Time Frame:24 months
Safety Issue:
Description:Determine TTP in each arm of the study
Measure:Duration of Response (DOR)
Time Frame:24 months
Safety Issue:
Description:Determine DOR in each arm of the study

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Acute Myeloid Leukemia
  • Myelodysplastic syndromes

Last Updated