Study of Tinostamustine, First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies

• Status: Recruiting
• Trial end date: 2022-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the efficacy, safety and pharmacokinetics of tinostamustine (EDO-S101) in patients with relapsed/refractory hematologic malignancies. All patients will receive tinostamustine.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Mundipharma-EDO GmbH

Criteria

Inclusion Criteria:

1. Patient willing and able to sign an informed consent.

2. Patients age ≥18 years at signing the informed consent.

3. Life expectancy > 3 months.

4. Diagnosis of relapsed or refractory lymphoid malignancy for which there are no available therapies.

5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2

6. Absolute Neutrophil Count >1,000 µL

7. Platelets ≥100,000 µL

8. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 upper limit of normal (ULN).

9. Total bilirubin <2.0 mg/dL unless elevated due to known Gilbert's syndrome.

10. Creatinine ≤1.5 x ULN.

11. 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).

12. 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 1. At least one line and a maximum of five prior standard systemic therapies and no other standard therapy available with proven clinical benefit.

Cohort 2: relapsed/refractory Hodgkin's lymphoma

1. At least three lines of prior 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)

1. Only CTCL patients with histologically or cytologically confirmed MF or SS with stage IIb to IVb disease based on modified ISCL/EORTC staging.

2. At least one line and a maximum of four prior standard systemic therapies and no other standard therapy available with proven clinical benefit.

Exclusion Criteria:

1. Patients with any central nervous system involvement.

2. Patient who had a hematologic malignancy that has transformed.

3. Any patient who has relapsed within 100 days of stem cell infusion following an allogenic or an autologous bone marrow transplant.

4. Patients with corrected QT (QTc) interval (Fridericia's formula) > 450 msec.

5. Patients who are on treatment with drugs known to prolong the QT/QTc interval.

6. Any serious medical condition that interferes with adherence to study procedures.

7. Patients with a history of another malignancy diagnosed within three years of study enrollment excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy.

8. Pregnant or breast feeding females.

9. New York Heart Association (NYHA) stage III/IV congestive heart failure. The following arrhythmias not adequately controlled, active: atrial fibrillation/flutter with poor rate control, documented sustained ventricular tachycardia (defined as >30 seconds or requiring cardioversion before 30 seconds have elapsed) or TdP.

10. Active infections, or other significant co-morbidities [(e.g., active central nervous system metastases and/or carcinomatous meningitis, active infection requiring systemic therapy, history of human immunodeficiency virus (HIV) infection, or active Hepatitis B or Hepatitis C.

11. Previous cancer therapies within three (3) weeks of dosing as long as the patient has recovered to eligibility levels prior to treatment in this study.

12. Use of other investigational agents within 30 days or 5 half-lives prior to the first dose of study drug unless patient has recovered from any related toxicities ≥ Grade 1.

13. Steroid treatment within seven (7) days prior to study treatment. Patients that require intermittent use of bronchodilators, topical steroids or local steroid injections will not be excluded from the study. Patients who have been stabilized to 10 mg PO QD or less seven (7) days prior to study drug administration are allowed.

14. Patients on Valproic Acid for any indication (epilepsy, mood disorder) must be excluded from the trial .