STIMULUS-MDS1: A Study of MBG453 in Combination With Hypomethylating Agents in Subjects With IPSS-R Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS).

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03946670
Collaborator
(none)
127
Enrollment
47
Locations
2
Arms
62.2
Anticipated Duration (Months)
2.7
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase II is a multicenter, randomized, two-arm parallel-group, double-blind, placebo-controlled study of MBG453 or placebo added to hypomethylating agents (azacitidine or decitabine) in adult subjects with IPSS-R intermediate, high or very high risk myelodysplastic syndrome (MDS) not eligible for Hematopoietic Stem Cell Transplant (HSCT) or intensive chemotherapy.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
127 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Supportive Care
Official Title:
A Randomized, Double-blind, Placebo-controlled Phase II Multi-center Study of Intravenous MBG453 Added to Hypomethylating Agents in Adult Subjects With Intermediate, High or Very High Risk Myelodysplastic Syndrome (MDS) as Per IPSS-R Criteria
Actual Study Start Date :
Jun 4, 2019
Anticipated Primary Completion Date :
Apr 29, 2022
Anticipated Study Completion Date :
Aug 10, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: MBG453 + hypomethylating agents

Patients will take MBG453 plus hypomethylating agents

Drug: MBG453
MBG453 will be administered i.v.

Drug: Hypomethylating agents
Decitabine will be administered i.v. Azacitidine will be administered i.v or s.c.

Placebo Comparator: Placebo + hypomethylating agents

Patients will take placebo plus hypomethylating agents

Drug: Placebo
Placebo will be administered i.v.

Drug: Hypomethylating agents
Decitabine will be administered i.v. Azacitidine will be administered i.v or s.c.

Outcome Measures

Primary Outcome Measures

  1. Complete remission (CR) rate [7 months after last patient first visit (LPFV)]

    Modified response criteria According to International Working Group (IWG) for Myelodysplastic syndromes (MDS) as per investigator assessment.

  2. Progression Free Survival (PFS) [Up to 20 months after Last Patient First Visit (LPFV)]

    Defined as time from randomization to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR according to IWG-MDS or death due to any cause, whichever occurs first, as per investigator assessment

Secondary Outcome Measures

  1. Overall Survival [Up to 4 years after LPFV]

    Time from randomization to death due to any cause

  2. Event Free Survival [Up to 4 years after LPFV]

    Time from randomization to lack of reaching CR within the first 6 months, relapse from CR or death due to any cause, whichever occurs first

  3. Leukemia-free survival [Up to 4 yrs after Last Patient First Visit (LPFV)]

    Time from randomization to ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification)or diagnosis of extramedullary acute leukemia or death due to any cause

  4. Response Rate (CR/mCR/PR/HI) [7 months after Last Patient First Visit (LPFV)]

    Percentage of complete remission(CR)/marrow Complete Remission (mCR)/partial remission (PR) and Hematological improvement (HI) according to IWG-MDS as per investigator assessment

  5. Duration of complete remission [Up to 4 yrs after Last Patient First Visit (LPFV)]

    Time from the date of the first documented CR to the date of first documented relapse from CR or death due to any cause, whichever occurs first

  6. Time to complete remission [7 months after Last Patient First Visit (LPFV)]

    Time from randomization to the first documented CR

  7. Percent of subjects who are red blood cells (RBC)/platelets transfusion independent after randomization as per IWG-MDS [Up to 4 years after last randomized patient]

    Improvement in RBC/platelets transfusion independence

  8. Red blood cells (RBC)/platelets transfusion independence duration after randomization [Up to 4 years after last randomized patient]

    Duration of transfusion independence

  9. Serum concentrations for MBG453 [At Day 8 of each cycle (1 cycle = 28 days) until cycle 6 and at day 8 of cycles 9, 12, 18 and 24, and up to 150 day of the safety follow up period]

    Pharmacokinetics of MBG453 when given in combination with hypomethylating agents (HMA)

  10. Immunogenicity of MBG453 when given in combination of hypomethylating agents [Up to 4 years after Last Patient First Visit (LPFV)]

    Anti-drug Antibody (ADA) prevalence at baseline and ADA incidence on-treatment

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Signed informed consent must be obtained prior to participation in the study.

  2. Age ≥ 18 years at the date of signing the informed consent form (ICF)

  3. Morphologically confirmed diagnosis of a myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al 2016) by investigator assessment with one of the following Prognostic Risk Categories, based on the International Prognostic Scoring

System (IPSS-R):
  • Very high

  • High

  • Intermediate with at least ≥ 5% bone marrow blast

  1. Not eligible at the time of screening, for intensive chemotherapy according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions

  2. Not eligible at the time of screening, for hematopoietic stem-cell transplantation (HSCT) according to the investigator, based on local standard medical practice and institutional guidelines for treatment decisions.

  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:
  1. Prior exposure to TIM-3 directed therapy at any time. Prior therapy with immune check point inhibitors (e.g. anti-CTLA4, anti-PD-1, anti-PD-L1, or anti-PD-L2), cancer vaccines are allowed except if the drug was administered within 4 months prior to randomization.

  2. Previous first-line treatment for higher risk MDS with chemotherapy or any other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine.

  3. History of severe hypersensitivity reactions to any ingredient of the study treatment (azacitidine, decitabine or MGB453) or their excipients, or to monoclonal antibodies (mAbs).

  4. Currently using or used within 14 days prior to randomization of systemic, steroid therapy (> 10 mg/day prednisone or equivalent) or any immunosuppressive therapy. Topical, inhaled, nasal, ophthalmic steroids are allowed. Replacement therapy, steroids given in the context of a transfusion are allowed and not considered a form of systemic treatment.

  5. Investigational treatment for MDS received within 4 weeks prior to randomization. In case of a checkpoint inhibitor: 4 months minimum prior to randomization interval is necessary to allow enrollment.

  6. Active autoimmune disease requiring systemic therapy (e.g.corticosteroids).

  7. Live vaccine administered within 30 Days prior to randomization.

Other protocol-defined Inclusion/Exclusion may apply.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1City of Hope National Medical Center Medical Oncology & TherapeuticDuarteCaliforniaUnited States91010
2Yale University School of MedicineNew HavenConnecticutUnited States06520
3Dana Farber Cancer Institute Centerfor Sarcoma&BoneOncologyBostonMassachusettsUnited States02215
4The Cancer Institute of New Jersey The Cancer Institute of NJNew BrunswickNew JerseyUnited States08901
5Ohio State Comprehensive Cancer Center/James Cancer Hospital SC- BCL201X2102CColumbusOhioUnited States73210
6Mary Crowley Cancer ResearchDallasTexasUnited States75251
7Novartis Investigative SiteViennaAustria1140
8Novartis Investigative SiteBrasschaatBelgium2930
9Novartis Investigative SiteLeuvenBelgium3000
10Novartis Investigative SiteTorontoOntarioCanadaM5G 1Z6
11Novartis Investigative SiteQuebecCanadaG1J 1Z4
12Novartis Investigative SiteBrno - BohuniceCzechia639 01
13Novartis Investigative SitePrahaCzechia12808
14Novartis Investigative SiteToulouseFrance31059
15Novartis Investigative SiteBerlinGermany13353
16Novartis Investigative SiteLeipzigGermany04103
17Novartis Investigative SiteAlexandroupolisEvrosGreece681 00
18Novartis Investigative SiteLarissaGRGreece411 10
19Novartis Investigative SitePatrasGreece265 00
20Novartis Investigative SiteHong KongHong Kong
21Novartis Investigative SiteDebrecenHungary4032
22Novartis Investigative SiteNyiregyhazaHungary4400
23Novartis Investigative SiteFirenzeFIItaly50134
24Novartis Investigative SiteMilanoMIItaly20162
25Novartis Investigative SiteRozzanoMIItaly20089
26Novartis Investigative SiteReggio CalabriaRCItaly89124
27Novartis Investigative SiteRomaRMItaly00133
28Novartis Investigative SiteFukuoka cityFukuokaJapan812-8582
29Novartis Investigative SiteFukushima cityFukushimaJapan960 1295
30Novartis Investigative SiteGifu shiGifuJapan500 8513
31Novartis Investigative SiteIseharaKanagawaJapan259-1193
32Novartis Investigative SiteKumamoto-cityKumamotoJapan860-0008
33Novartis Investigative SiteSendai-shiMiyagiJapan983 8520
34Novartis Investigative SiteNagasaki-cityNagasakiJapan852-8501
35Novartis Investigative SiteBunkyo kuTokyoJapan113-8677
36Novartis Investigative SiteOsakaJapan545-8586
37Novartis Investigative SiteSeoulKorea, Republic of03080
38Novartis Investigative SiteSeoulKorea, Republic of06351
39Novartis Investigative SiteMalagaAndaluciaSpain29010
40Novartis Investigative SiteSantanderCantabriaSpain39008
41Novartis Investigative SiteHospitalet de LLobregatCatalunyaSpain08907
42Novartis Investigative SiteKaohsiung CityTaiwan83301
43Novartis Investigative SiteTaipeiTaiwan10002
44Novartis Investigative SiteIzmirTurkey35040
45Novartis Investigative SiteKocaeliTurkey41380
46Novartis Investigative SiteSamsunTurkey55139
47Novartis Investigative SiteManchesterUnited KingdomM20 4BX

Sponsors and Collaborators

  • Novartis Pharmaceuticals

Investigators

  • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT03946670
Other Study ID Numbers:
  • CMBG453B12201
  • 2018-004479-11
First Posted:
May 13, 2019
Last Update Posted:
Feb 2, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 2, 2022