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
Details
Status
Open: Currently recruiting participants.
Closed: Recruitment either has not started or has paused or completed.
Study Type
Interventional (clinical trials): Test treatments.
Observational: Conduct surveys and interviews, study medical records and otherwise observe people or groups over time.
Interventional
Study Phase
Each study phase tests different aspects of the medication or treatment:
- Phase I: safety and dosing
- Phase II: effectiveness and side effects
- Phase III: efficacy compared to standard treatments
- Phase IV: long-term safety after approval for use
I
Location(s)
Johns Hopkins study sites. Additional study locations may be found on ClinicalTrials.gov.
The Johns Hopkins Hospital
1800 Orleans St Baltimore, MD 21287
Keywords
Contact Us
(410) 955-8964Brief Summary
Approximately 80 participants in several countries will be enrolled. 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.
The following two DFV890 doses will be studied in the randomized dose optimization part: 25 mg and 50 mg administered orally twice daily (BID) as tablets. Once the single agent RD is identified, a protocol amendment may be issued to evaluate DFV890 in combination with other agents (e.g. ESA or HMA) in patients with LR MDS or LR CMML.
Eligibility
Key Inclusion Criteria:
Patients must be ≥ 18 years of age at the time of signing the informed consent form (ICF)
The Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
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.
Patients must have one of the following for eligibility into the study:
- In dose optimization and expansion: 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
- 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.
Key Exclusion Criteria:
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.
History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
Patients who have previously been treated with agents that have the same mechanism of action as DFV890 as defined in Table 6-8, list of prohibited medications (e.g., drugs targeting the NLRP3 inflammasome pathway and the IL-1 pathway (canakinumab and anakinra)).
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.
Patients receiving:
- 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
- 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.
Other protocol-defined inclusion/exclusion criteria may apply.