Loading clinical trials...

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases | Clinical Trials | Clareo Health

ACTIVE_NOT_RECRUITINGPHASE1

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases

A Phase 1b, Open Label, Multi-center, Dose Optimization and Dose Expansion Study to Assess the Safety and Efficacy of DFV890 in Adult Patients With Myeloid Diseases

NCT05552469•Novartis Pharmaceuticals

View on ClinicalTrials.gov

Summary

Study CDFV890G12101 is an open-label, phase 1b, multicenter study with a randomized two-dose optimization part, and a dose expansion part consisting of three groups evaluating DFV890 in patients with myeloid diseases. The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, efficacy and recommended dose for single agent DFV890 in patients with lower risk (LR: very low, low or intermediate risk) myelodysplastic syndromes (LR MDS), lower risk chronic myelomonocytic leukemia (LR CMML) and High-Risk Clonal Cytopenia of Undetermined Significance (HR CCUS).

Detailed Description

This research study is to find out if study treatment DFV890 is safe and tolerable, and can help patients who were diagnosed with a myeloid disease such as: very low, low or intermediate risk myelodysplastic syndromes (MDS), very low, low or intermediate risk chronic myelomonocytic leukemia (CMML) and High-Risk Clonal Cytopenia of Undetermined Significance (HR CCUS). The study seeks to determine the optimal dose of DFV890 that is safe and efficacious in patients with myeloid disease. The effectiveness and safety/tolerability of the study treatment is not yet confirmed in this disease setting. Eligible patients meeting all study entry requirements will be required to provide a sample from their bone marrow at screening and at select study timepoints. All enrolled patients will be dosed for a minimum of twenty-four weeks (6 cycles of treatment) unless they experience side effects related to the study treatment requiring dose interruption/discontinuation, worsening of the disease, and/or if treatment is discontinued at the discretion of the investigator or the patient.

Eligibility

Age

18 - 100 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1\. Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF) 2. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2 3. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to the institutions guidelines and must be willing to undergo a bone marrow aspirate.
•4\. Patients must have one of the following for eligibility into the study:
•1. In dose optimization: IPSS-R defined very low, low or intermediate risk Myelodysplastic Syndrome (LR MDS) who failed to respond to or did not tolerate ESAs or luspatercept or HMAs and patients with del 5q who failed to respond to or did not tolerate lenalidomide; or
•2. In dose optimization and expansion: IPSS-R defined very low, low or intermediate risk Chronic Myelomonocytic Leukemia (LR CMML) who failed to respond to or did not tolerate hydroxyurea or HMAs.
•3. changes for dose expansion (applicable as of amendment 3):
•1. LR MDS with ≤ 10% bone marrow blasts, IPSS-R score of ≤ 3.5, transfusion independent (TID) status as per IWG 2006 criteria (requiring \<4U pRBC in 8 weeks), clinically meaningful cytopenia(s) and no or limited (\<4 months) prior therapy for MDS.
•2. LR CMML patients with symptomatic cytopenias and/or constitutional symptoms refractory, intolerant or unsuitable for standard first-line therapy.
•3. HR-CCUS: Diagnosis of high-risk CCUS by clonal hematopoiesis risk score (CHRS) with clinically meaningful cytopenias and no prior therapy for a myeloid neoplasm.

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 28 days or 5 half-lives, whichever is longer, and recovered from the toxicities before the first dose of study treatment. For patients that received antibodies the washout period is 4 weeks prior to study treatment.
•a. For TID LR MDS in Dose Expansion Phase only (applicable as of amendment 03):
•1. Prior therapy for MDS administered for \>4 months (ESA and luspatercept administered for ≤4 months will be allowed if washout period followed)
•2. Concurrent malignancy requiring active systemic therapy
•3. Prior or concurrent cytotoxic chemotherapy for MDS at any time
•2\. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
•3\. Patients who have previously been treated with agents that have the same mechanism of action as DFV890 as defined in Table 6-7, list of prohibited medications (e.g., drugs targeting the NLRP3 inflammasome pathway and the IL-1 pathway (canakinumab and anakinra)).
•4\. Use of hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF, M-CSF), thrombopoietin mimetics or erythroid stimulating agents anytime ≤ 1 week (or 5 half lives, whichever is longer) prior to start of study treatment.
•5\. Patients receiving:
•a. concomitant medications that are known to be modulators of cytochrome P450 enzymes CYP2C9 and/or CYP3A (specifically strong or moderate inducers of CYP2C9, strong inducers of CYP3A enzymes, strong inhibitors of CYP2C9 and/or strong or moderate dual inhibitors of CYP2C9/CYP3A); and b. patients, who are poor CYP2C9 metabolizers receiving concomitant medications known to be strong or moderate inhibitors of CYP3A, whose concomitant medications cannot be discontinued or switched to a different medication within 5 half-lives or 1 week (whichever is longer) prior to start of study treatment and for duration of the study. See Section 6.8 and list of prohibited drugs in Appendix 8 for more details.
+1 more criteria

Locations (26)

Stanford Cancer Center

Stanford, California, United States

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

Sidney Kimmel CCC At JH

Baltimore, Maryland, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Mayo Clinic Rochester

Rochester, Minnesota, United States

Weill Cornell Medicine NY-Presb

New York, New York, United States

Memorial Sloan Kettering Cancer Ctr

New York, New York, United States

Vanderbilt University Medical Ctr

Nashville, Tennessee, United States

Univ of TX MD Anderson Cancer Cntr

Houston, Texas, United States

Key Dates

Start Date

May 8, 2023

Primary Completion Date

January 29, 2027

Completion Date

February 1, 2027

Last Updated

March 10, 2026

Enrollment

ACTUAL participants

Conditions

Myeloid Diseases

Interventions

DFV890

DRUG