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Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS

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ClinicalTrials.gov Identifier: NCT04810611
Recruitment Status : Recruiting
First Posted : March 23, 2021
Last Update Posted : July 12, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
The purpose of this study is to characterize the safety, tolerability and confirm the dose for select single agents and combinations in patients with lower risk (very low, low, and intermediate risk) MDS.

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: MBG453 Drug: NIS793 Drug: canakinumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome
Actual Study Start Date : June 18, 2021
Estimated Primary Completion Date : February 16, 2024
Estimated Study Completion Date : February 16, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Canakinumab

Arm Intervention/treatment
Experimental: Arm 1: MBG453 single agent
Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.
Drug: MBG453
Anti-TIM3 monoclonal antibody

Experimental: Arm 2: NIS793 single agent
Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.
Drug: NIS793
Anti-TGF-β monoclonal antibody

Experimental: Arm 3: canakinumab single agent
Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.
Drug: canakinumab
Anti-IL-1β monoclonal antibody
Other Name: ACZ885

Experimental: Arm 4: MBG453 + NIS793 combination
Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.
Drug: MBG453
Anti-TIM3 monoclonal antibody

Drug: NIS793
Anti-TGF-β monoclonal antibody

Experimental: Arm 5: MBG453 + canakinumab combination
Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.
Drug: MBG453
Anti-TIM3 monoclonal antibody

Drug: canakinumab
Anti-IL-1β monoclonal antibody
Other Name: ACZ885




Primary Outcome Measures :
  1. Dose interruption reduction [ Time Frame: 30 Months ]
    Dose tolerability

  2. Incidence of DLTs [ Time Frame: 30 Months ]
    Incidence of dose limiting toxicities (DLTs) during the first 2 cycle of treatment during the dose escalation/confirmation part

  3. Dose intensity [ Time Frame: 30 Months ]
    Dose tolerability

  4. AE and SAE indicence [ Time Frame: 30 months ]
    Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment


Secondary Outcome Measures :
  1. Efficacy of single agents and combinations on transfusion dependent patients: Best Overall Response (BOR) [ Time Frame: 30 Months ]
    Evaluate change in transfusion burden and hematologic parameters

  2. Efficacy of single agents and combinations on transfusion dependent patients: Duration of Response (DOR) [ Time Frame: 30 Months ]
    Evaluate change in transfusion burden and hematologic parameters

  3. Efficacy of single agents and combinations on transfusion dependent patients: Progression free survival (PFS) [ Time Frame: 30 Months ]
    Evaluate change in transfusion burden and hematologic parameters

  4. Efficacy of single agents and combinations on transfusion dependent patients: Time to progression (TTP) [ Time Frame: 30 Months ]
    Evaluate change in transfusion burden and hematologic parameters

  5. Efficacy of single agents and combinations in patients who are transfusion independent: Best Overall Response (BOR) [ Time Frame: 30 Months ]
    Evaluate change in hematologic parameters

  6. Efficacy of single agents and combinations in patients who are transfusion independent: Duration of Response (DOR) [ Time Frame: 30 Months ]
    Evaluate change in hematologic parameters

  7. Efficacy of single agents and combinations in patients who are transfusion independent: Progression Free Survival (PFS) [ Time Frame: 30 Months ]
    Evaluate change in hematologic parameters

  8. Efficacy of single agents and combinations in patients who are transfusion independent: Time to Progression (TTP) [ Time Frame: 30 Months ]
    Evaluate change in hematologic parameters

  9. Characterize pharmacokinetics for single agents and combinations: Cmax [ Time Frame: 30 Months ]
    Serum concentrations and derived PK parameters

  10. Characterize pharmacokinetics for single agents and combinations: Tmax [ Time Frame: 30 Months ]
    Serum concentrations and derived PK parameters

  11. Characterize pharmacokinetics for single agents and combinations: Ctrough [ Time Frame: 30 Months ]
    Serum concentrations and derived PK parameters

  12. Characterize the prevalence of immunogenicity [ Time Frame: 30 Months ]
    Anti-drug antibody prevalence at baseline and on treatment.

  13. Efficacy of single agents and combinations on transfusion dependent patients: Overall Response Rate (ORR) [ Time Frame: 30 Months ]
    Evaluate change in transfusion burden and hematologic parameters

  14. Efficacy of single agents and combinations in patients who are transfusion independent: Overall Response Rate (ORR) [ Time Frame: 30 Months ]
    Evaluate change in hematologic parameters



Information from the National Library of Medicine

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.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  1. Signed informed consent must be obtained prior to participation in the study.
  2. Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF).
  3. Patients must have a diagnosis prior to participation in the study of IPSS-R very low, low, or intermediate risk MDS with ≤10% bone marrow blasts and one or more of the following:

    1. Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is refractory to ESAs (or the patient is intolerant to ESAs)
    2. Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level ≥ 500 /uL
    3. Thrombocytopenia with platelets <30,000/uL or with clinically significant bleeding or bruising and platelets <50,000/uL
    4. Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent and/or severe infections and an ANC that is <1000/ µL and amenable to response assessments by International Working Group (IWG) response criteria in myelodysplasia (Cheson et al 2006)
  4. Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC therapeutic options including lenalidomide
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2
  6. 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/or biopsy at screening, during and at the end of therapy on this study -

Key Exclusion Criteria:

  1. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon, kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or any experimental therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of study treatment.
  2. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes.
  3. Patients with chronic myelomonocytic leukemia (CMML) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
  4. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or ESAs anytime ≤ 2 weeks (or 5 half-lives, whichever is longer) prior to start of study treatment.
  5. Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal and ophthalmic steroids are allowed.
  6. For arms containing canakinumab: Patients with ANC < 500 /µL

Information from the National Library of Medicine

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): NCT04810611


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Ohio
The Ohio State University Wexner Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Ashley Tyson    641-239-3316    Ashley.Tyson@osumc.edu   
Principal Investigator: Uma Borate         
United States, Texas
MD Anderson Cancer Center/University of Texas MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Bailey Mirabella    713-792-7305    BLMirabella@mdanderson.org   
Principal Investigator: Guillermo Garcia-Manero         
Australia, Victoria
Novartis Investigative Site Recruiting
Prahran, Victoria, Australia, 3181
China, Tianjin
Novartis Investigative Site Recruiting
Tianjin, Tianjin, China, 300020
Israel
Novartis Investigative Site Recruiting
Tel Aviv, Israel, 6423906
Italy
Novartis Investigative Site Recruiting
Milano, MI, Italy, 20162
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 03080
Singapore
Novartis Investigative Site Recruiting
Singapore, Singapore, 119228
Novartis Investigative Site Recruiting
Singapore, Singapore, 169608
Spain
Novartis Investigative Site Recruiting
Salamanca, Castilla Y Leon, Spain, 37007
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04810611    
Other Study ID Numbers: CMBG453E12101
First Posted: March 23, 2021    Key Record Dates
Last Update Posted: July 12, 2022
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Myelodysplastic
myelodysplastic syndrome
MDS
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms