A Phase 1 Trial to Investigate the Safety, Pharmacokinetic Profiles and the Efficacy of Tinostamustine, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies
This study evaluates the efficacy, safety and pharmacokinetics of tinostamustine (EDO-S101) in patients with relapsed/refractory hematologic malignancies. All patients will receive tinostamustine.
• Patient willing and able to sign an informed consent.
• Patients age ≥18 years at signing the informed consent.
• Life expectancy \> 3 months.
• Diagnosis of relapsed or refractory lymphoid malignancy for which there are no available therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2
• Absolute Neutrophil Count \>1,000 µL
• Platelets ≥100,000 µL
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 upper limit of normal (ULN).
• Total bilirubin \<2.0 mg/dL unless elevated due to known Gilbert's syndrome.
⁃ Creatinine ≤1.5 x ULN.
⁃ Serum potassium and magnesium at least at the lowest limit of normal (LLN) at baseline(before every IMP administration; if it is below LNN, (supplementation is permissible).
⁃ Males and females of child-bearing potential, and their partners, must be willing to use at least two effective forms of birth control during the study drug administration and for at least 90 days after the administration of the study drug to be eligible to participate. Vasectomized partners and patients must be willing to use a secondary method of effective birth control. Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient.
‣ Specific Eligibility Criteria for Each Patient Cohort in Stage 2 Phase of the Study
‣ Cohort 1: relapsed/refractory multiple myeloma (Recruitment to this cohort stopped Dec 2021) 1. At least one line of prior systemic therapy and no other standard therapy available with proven clinical benefit.
‣ Cohort 2: relapsed/refractory Hodgkin's lymphoma
• At least two lines of prior therapy and no other standard therapy available with proven clinical benefit.
‣ Cohort 3: PTCL (recruitment to this cohort stopped March 2021)
• Only PTCL patients with histologically or cytologically confirmed Peripheral T-Cell Lymphoma - Not Otherwise Specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or Anaplastic Large Cell Lymphoma (ALCL).
• At least one line of prior combination therapy and no other standard therapy available with proven clinical benefit
‣ Cohort 4: relapsed/refractory cutaneous T-cell lymphoma (CTCL), subtypes mycosis fungoides (MF) and Sézary syndrome (SS)
• Only CTCL patients with histologically or cytologically confirmed MF or SS with stage IIb to IVb disease based on modified ISCL/EORTC staging.
• At least one line and a maximum of four prior standard systemic therapies and no other standard therapy available with proven clinical benefit.
‣ Cohort 5: PTCL (Recruitment to this cohort stopped March 2021)
‣ Eligibility criteria for sub study:
‣ Diagnosis of relapsed or refractory lymphoma, including Diffuse large B cell lymphoma who failed at least 2 lines of prior systemic therapy, Hodgkin lymphoma who failed at least 3 lines of prior systemic therapy, follicular lymphoma grade 1-3a, marginal zone lymphoma and mantle cell lymphoma who failed at least 2 lines of prior systemic lines of prior therapy, T cell lymphoma (including PTCL, CTCL) who failed at least 2 lines of prior systemic therapy for which there are no available therapies. Patients with bulky disease and Multiple Myeloma patients are excluded from this sub study.