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A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies (BEXMAB)

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ClinicalTrials.gov Identifier: NCT05428969
Recruitment Status : Recruiting
First Posted : June 23, 2022
Last Update Posted : January 17, 2024
Sponsor:
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

Tracking Information
First Submitted Date  ICMJE June 15, 2022
First Posted Date  ICMJE June 23, 2022
Last Update Posted Date January 17, 2024
Actual Study Start Date  ICMJE June 2, 2022
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2022)
  • Reporting of incidence and frequency of dose limiting toxicities (DLTs). [ Time Frame: From study start to end of Cycle 1 (each cycle is 28 days) ]
  • Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and serious adverse events (SAE). [ Time Frame: From study start to 30 days after end of treatment (EOT) ]
  • Complete response (CR) rate for MDS and CMML-2. [ Time Frame: From study start to 30 days after EOT ]
  • Overall response rate (ORR) for MDS and CMML failure to prior HMA. [ Time Frame: From study start to 30 days after EOT ]
  • Complete remission with incomplete blood recovery (CRi) for r/r AML. [ Time Frame: From study start to 30 days after EOT ]
  • Minimal residual disease (MRD) status for newly diagnosed AML. [ Time Frame: From study start to 30 days after EOT ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2022)
  • Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs. [ Time Frame: From study start to 30 days after EOT ]
  • Clinical efficacy measures based on progression free survival analyses defined as the time from study start to the date of documented disease progression or death from any cause, whichever occurs first, up to 2 years. [ Time Frame: 24 months from study start ]
  • Clinical efficacy measures based on overall survival analyses defined as the length measured from study start to death from any cause up to 2 years. [ Time Frame: 24 months from study start ]
  • Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment. [ Time Frame: 24 months from study start ]
  • Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood. [ Time Frame: From study start to end of Cycle 2 (each cycle is 28 days) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 17, 2022)
  • Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs. [ Time Frame: From study start to 30 days after EOT ]
  • Clinical efficacy measures based on disease progression analyses. [ Time Frame: 24 months from study start ]
  • Clinical efficacy measures based on survival analyses. [ Time Frame: 24 months from study start ]
  • Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment. [ Time Frame: 24 months from study start ]
  • Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood. [ Time Frame: From study start to end of Cycle 2 (each cycle is 28 days) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies (BEXMAB)
Official Title  ICMJE Phase I/II Open-Label Study to Assess Safety, Tolerability and Preliminary Efficacy of the CLEVER-1 Antibody Bexmarilimab in Combination With Azacitidine or Azacitidine/Venetoclax in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia
Brief Summary This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of bexmarilimab based on safety, tolerability and pharmacological activity; Phase 2 will investigate the preliminary efficacy of the combination treatment in selected indications from Phase 1.
Detailed Description

This is a multicenter Phase 1/2 open-label, study to assess the safety, tolerability and preliminary efficacy of increasing doses of bexmarilimab (FP-1305) in patients with intermediate, high or very high-risk MDS, CMML with 10-19 % marrow blasts, CMML/MDS with failure to hypomethylating agent (HMA), or in patients with newly diagnosed AML non-fit for induction therapy or relapsed/refractory AML. The Phase 1 part of the study will identify a safe and tolerable bexmarilimab dose amongst four predefined dose levels using a bayesian optimal interval (BOIN) dose escalation design to identify the maximum tolerated dose (MTD) of bexmarilimab when administered in combination with SoC.

The Phase 2 of the study is an expansion phase to further evaluate the safety and preliminary efficacy of bexmarilimab treatment at RP2D combined with SoC and will follow a Simon's 2-stage design for each of the indications selected to continue forward from Phase 1. This design allows for the investigation of bexmarilimab activity and preliminary response assessments tailored to each indication and allows early stopping in case of futility using a minimum number of patients. Patients from Phase 1, with the selected indication to be investigated in Phase 2, that have been treated at RP2D may be counted towards the number of patients for Phase 2.

Both study phases consist of a screening period, a treatment period, an end of treatment (EoT) as safety follow-up and disease progression/survival follow-up.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
  • Relapsed/Refractory AML
Intervention  ICMJE
  • Drug: Bexmarilimab
    Intravenous
    Other Name: FP-1305
  • Drug: Azacitidine
    As per label, subcutaneous
  • Drug: Venetoclax
    Oral
    Other Name: Venclyxto®
Study Arms  ICMJE
  • Experimental: Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML
    Standard of care azacitidine as per label; bexmarilimab 4 dose levels at once every week (Q1W) followed by once every 2 weeks (Q2W); 28-day cycle
    Interventions:
    • Drug: Bexmarilimab
    • Drug: Azacitidine
  • Experimental: Phase 1 - Newly diagnosed AML patients non-fit for induction therapy
    Standard of care azacitidine and venetoclax as per label; bexmarilimab 4 dose levels Q1W followed by Q2W; 28-day cycle
    Interventions:
    • Drug: Bexmarilimab
    • Drug: Azacitidine
    • Drug: Venetoclax
  • Experimental: Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML
    Standard of care venetoclax and/or azacitidine as per label plus bexmarilmab
    Interventions:
    • Drug: Bexmarilimab
    • Drug: Azacitidine
    • Drug: Venetoclax
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: June 17, 2022)
181
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date December 31, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient ≥ 18 years of age who presents with one of the following conditions:

    • Morphologically confirmed diagnosis of MDS with revised International Prognostic Scoring System (rIPSS) risk categories: intermediate, high and very high.
    • Morphologically confirmed diagnosis of CMML-2 with indication for azacitidine treatment.
    • CMML and MDS patient with response failure to HMA or therapy regimen including HMA.
    • Morphologically confirmed diagnosis of r/r AML following at least 1 line of prior therapies with indication for azacitidine treatment.
    • Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment.
  • Leukocyte count < 20 x10^9/L (< 25 x10^9/L for newly diagnosed AML). Hydroxycarbamide use is permitted to meet this criterion in MDS and AML but not in CMML.
  • Adequate renal function.
  • Adequate liver function.

Exclusion Criteria:

  • Patient with acute promyelocytic leukemia (APL) or myeloproliferative CMML as defined by leukocyte count > 13 x10^9/L.
  • Eastern Cooperative Oncology Group (ECOG) performance status >2 (except newly diagnosed AML where ECOG 3 is allowed for patients < 75 years).
  • Allogeneic transplantation less than 6 months prior screening.
  • Patient with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia).
  • The patient requires systemic corticosteroid (≥10 mg/day prednisone or equivalent) or other immunosuppressive treatment.
  • Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than 14 days or five half-lives (whichever is shorter) from a small molecule targeted therapy or oral anticancer chemotherapy before the first study treatment.
  • Any immunotherapy or investigational therapy within preceding 28 days from the first study treatment.
  • Pregnant or lactating women.
  • History of chronic ulcers or clinically relevant liver disease leading to Child Pugh Score C or higher.
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: Inka Pawlitzky, PhD +358 2 4695151 inka.pawlitzky@faron.com
Listed Location Countries  ICMJE Finland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05428969
Other Study ID Numbers  ICMJE FP2CLI004
2021-002104-12 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 Not Provided
Current Responsible Party Faron Pharmaceuticals Ltd
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Faron Pharmaceuticals Ltd
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mika Kontro, MD, PhD Helsinki University Central Hospital
PRS Account Faron Pharmaceuticals Ltd
Verification Date November 2023

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