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

NCT02576496 | Completed Phase 1 DMC

• 1 other identifier: EDO-S101-1001
• Study Type: interventional
• Target: 106
• Locations: 7 countries
• Sites: 18

Brief 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.

Conditions

Hematological Malignancies; Multiple Myeloma; Hodgkin's Lymphoma; Cutaneous T Cell Lymphoma

Keywords

phase 1 clinical trial; multiple myeloma; Hodgkin's lymphoma; cutaneous T-cell lymphoma; tinostamustine

Outcome Measures

Primary Outcomes (2)

• Overall response rate

  Determine overall response rate

  10-20 months from beginning of stage 2

• Clinical benefit rate by cohort

  Determine clinical benefit rate by cohort

  10-20 months from beginning of stage 2

Secondary Outcomes (4)

• Time to objective response

  10-20 months after beginning stage 2

• Duration of response

  10-20 months after beginning stage 2

• Progression free survival (PFS)

  32-36 months after beginning stage 2

• Overall Survival (OS)

  32-36 months after beginning stage 2

Study Arms (15)

Tinostamustine 20mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 40mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 60mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 80mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 100mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 120mg/m2 over 60min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 80mg/m2 over 45min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 60mg/m2 over 30min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Tinostamustine 80mg/m2 over 30min

EXPERIMENTAL

Tinostamustine as a single agent administered by IV infusion on D1 of 21-day cycle.

Drug: Tinostamustine

Stage 2 cohort 1: relapsed/refractory Multiple Myeloma

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 60mg/m2 by IV infusion over 60min on D1 and D15 of 28-day cycle.

Drug: Tinostamustine

Stage 2 cohort 2: relapsed/refractory Hodgkin Lymphoma

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.

Drug: Tinostamustine

Stage 2 cohort 3: relapsed/refractory peripheral T-cell lymphoma (PTCL)

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.

Drug: Tinostamustine

Stage 2 cohort 4: relapsed/refractorycutaneous T-cell lymphoma (CTCL)

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle. Patients are of subtypes mycosis fungoides (MF) or Sézary syndrome (SS).

Drug: Tinostamustine

Stage 2 cohort 5: relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL)

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 60min on D1 of 21-day cycle.

Drug: Tinostamustine

Substudy

EXPERIMENTAL

Tinostamustine as a single agent administered at a dose of 100mg/m2 by IV infusion over 100min on D1 of 21-day cycle.

Drug: Tinostamustine

Interventions

Tinostamustine DRUG

Also known as: EDO-S101

Stage 2 cohort 1: relapsed/refractory Multiple Myeloma; Stage 2 cohort 2: relapsed/refractory Hodgkin Lymphoma; Stage 2 cohort 3: relapsed/refractory peripheral T-cell lymphoma (PTCL); Stage 2 cohort 4: relapsed/refractorycutaneous T-cell lymphoma (CTCL); Stage 2 cohort 5: relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL); Substudy; Tinostamustine 100mg/m2 over 60min; Tinostamustine 120mg/m2 over 60min; Tinostamustine 20mg/m2 over 60min; Tinostamustine 40mg/m2 over 60min; Tinostamustine 60mg/m2 over 30min; Tinostamustine 60mg/m2 over 60min; Tinostamustine 80mg/m2 over 30min; Tinostamustine 80mg/m2 over 45min; Tinostamustine 80mg/m2 over 60min

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Patients with any central nervous system involvement.
• Patient who had a hematologic malignancy that has transformed.
• Any patient who has relapsed within 100 days of stem cell infusion following an allogenic or an autologous bone marrow transplant.
• Patients with corrected QT (QTc) interval (Fridericia's formula) \> 450 msec.
• Patients who are on treatment with drugs known to prolong the QT/QTc interval.
• Any serious medical condition that interferes with adherence to study procedures.
• 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.
• Pregnant or breast feeding females.
• 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.
• 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.
• 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.
• 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.
• 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.
• Patients on Valproic Acid for any indication (epilepsy, mood disorder) must be excluded from the trial .

Sponsors & Collaborators

• Mundipharma Research Limited: lead

Study Sites (18)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Cancer Center

Jacksonville, Florida, 32224, United States

Location

Columbia University Medical Center

New York, New York, 10019, United States

Location

University Hospitals Cleveland Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

CHU de Caen

Caen, CS 3001, France

Location

CHU ESTAING Service de thérapie Cellulaire et hématologique Clinique

Clermont-Ferrand, 63000, France

Location

CHU Lille Service des Maladies du Sang

Lille, 59037, France

Location

Hopital Haut Leveque

Pessac, 33604, France

Location

Centre hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

University Hospital of Ulm, Department of Internal Medicine III

Ulm, 89081, Germany

Location

Institute of Hematology "L. A. Seràgnoli", University of Bologna

Bologna, 40138, Italy

Location

National Cancer Institute, Fondazione 'G. Pascale'

Naples, I-80131, Italy

Location

VU medisch centrum

Amsterdam, 1081 HV, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Institut Català d'Oncologia de Barcelona

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Kantonsspital St.Gallen

Sankt Gallen, 9007, Switzerland

Location

Related Publications (1)

• Sureda A, Pinto A, Ghesquieres H, Morschhauser F, Tournilhac O, Mutsaers P, Zijlstra JM, De Filippi R, Hilgier K, Manamley N, Janik T, Zinzani PL. Safety and Efficacy of Tinostamustine in a Subpopulation of Patients With Relapsed/Refractory Hodgkin Lymphoma From a Phase I Trial. Hematol Oncol. 2025 Jan;43(1):e70000. doi: 10.1002/hon.70000.

  PMID: 39617826 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms; Multiple Myeloma; Hodgkin Disease; Lymphoma, T-Cell, Cutaneous

Interventions

tinostamustine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Lymphoma; Lymphatic Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin

Study Officials

• Pier L Zinzani, MD,PhD

  University of Bologna Medical Center, Bologna

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 15, 2015
• Study Start: April 14, 2016
• Primary Completion: May 30, 2023
• Study Completion: November 21, 2023
• Last Updated: July 25, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Available on request through Enquiries@napp.co.uk
• Access Criteria: Available on request through Enquiries@napp.co.uk

Locations

US (4); NL (2); ES (3); DE (1); FR (5); CH (1); IT (2)