Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of EDO-S101, A First-in-Class Alkylating HDACi Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02576496
Recruitment Status : Active, not recruiting
First Posted : October 15, 2015
Last Update Posted : May 30, 2019
Sponsor:
Information provided by (Responsible Party):
Mundipharma-EDO GmbH

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

Condition or disease Intervention/treatment Phase
Hematological Malignancies Multiple Myeloma Hodgkin's Lymphoma Peripheral T-cell Lymphoma Cutaneous T Cell Lymphoma T-cell Prolymphocytic Leukemia Drug: EDO-S101 Phase 1

Detailed Description:

EDO-S101 is a new chemical entity, a first-in-class fusion molecule of an alkylator, bendamustine and a histone-deacetylase inhibitor (HDACi), vorinostat. It is anticipated that EDO-S101 may have activity in various hematological malignancies and solid tumors. This phase 1 study will enroll patients with various hematological malignancies.

The study consists of 2 stages:

  • Stage 1: Dose Escalation to determine Maximum Tolerated Dose (MTD) at the optimal infusion time and the pharmacokinetic (PK) profiles; is expected to enroll between 21 and 48 patients. Stage 1 has now been completed.
  • Stage 2: Expansion in five Cohorts, in which approximately 6-16 patients will be enrolled per cohort, for a maximum of 65 patients.

In Stage 1, EDO-S101 doses will be escalated following the standard 3+3 design. The decision to escalate to the next dose level will occur after all cohort patients have completed 3 weeks (21 days) of observation and have been evaluated for safety and toxicity.The starting dose is a 1 hour infusion of 20 mg/m2, and the maximum dose level is 150 mg/m2. Reduced infusion times of 45 minutes and 30 minutes will also be assessed once the maximum tolerated dose at a 1-hour infusion is determined.

In Stage 2, five cohorts of patients (with relapsed/refractory multiple myeloma (MM); relapsed/refractory Hodgkin's lymphoma; relapsed/refractory peripheral T-cell lymphoma (PTCL); relapsed/refractory cutaneous T-cell lymphoma (CTCL); and relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL) will be enrolled and treated at the recommended Phase 2 dose (RP2D) based on results of Stage 1. For MM patients, treatment will occur on Day 1 and Day 15 of a 28 day cycle. For lymphoma patients, treatment will occur on Day 1 of a 21 day cycle. Patients in each stage of the study are expected to receive a median of four Cycles of therapy, and the maximum number of treatment Cycles allowed is 12.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 111 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study to Investigate the Safety, Pharmacokinetic Profiles and the Efficacy of EDO-S101, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Relapsed/Refractory Hematologic Malignancies
Study Start Date : March 2016
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : May 2021


Arm Intervention/treatment
Experimental: EDO-S101
EDO-S101, IV, 20mg/m2 up to 150mg/m2 Day1 of each 21 day cycle-Stage 1; EDO-S101,IV, 40mg/m2 up to 60mg/m2 on Day 1 and Day 15 of 28 day cycle in multiple myeloma patients and IV, 40mg/m2 up to 100mg/m2 on Day 1 of 21 day cycle in lymphoma patients-Stage 2
Drug: EDO-S101



Primary Outcome Measures :
  1. Classification of each stage 2 cohort as to interest or no interest based upon overall response rate [ Time Frame: 10-20 months from beginning stage 2 ]
    Determine overall response rate by cohort

  2. Overall response rate [ Time Frame: 10-20 months from beginning of stage 2 ]
    Determine overall response rate

  3. Clinical benefit rate by cohort [ Time Frame: 10-20 months from beginning of stage 2 ]
    Determine clinical benefit rate by cohort

  4. Safety of selected doses in expanded population [ Time Frame: 36 months from beginning stage 2 ]
    Number of participants with treatment-related adverse events as assessed by CTCAE V4.03


Secondary Outcome Measures :
  1. Time to overall response [ Time Frame: 10-20 months after beginning stage 2 ]
    Determine time to overall response by cohort

  2. Time to complete response [ Time Frame: 10-20 months after beginning stage 2 ]
    Determine time to complete response by cohort

  3. Duration of response [ Time Frame: 10-20 months after beginning stage 2 ]
    Determine duration of response by cohort

  4. Progression free survival (PFS) [ Time Frame: 32-36 months after beginning stage 2 ]
    Determine time to progression free survival by cohort

  5. Overall Survival (OS) [ Time Frame: 32-36 months after beginning stage 2 ]
    Determine the overall survival time by cohort

  6. PK trough profiles [ Time Frame: 10-20 months after beginning stage 2 ]
    Determine the trough PK profiles for EDO-S101



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Execute an informed consent.
  2. Patients age ≥18 years at signing the informed consent.
  3. Diagnosis of relapsed or refractory lymphoid malignancy for which there are no available therapies.
  4. Eastern Cooperative Oncology Group (ECOG) performance status ≤2
  5. Neutrophils >1,000 µL
  6. Platelets ≥75,000 µL
  7. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 upper limit of normal (ULN).
  8. Total bilirubin <2.0 mg/dL unless elevated due to known Gilbert's syndrome.
  9. Creatinine ≤1.5 ULN.
  10. Serum potassium within normal range (potassium supplementation is permissable).
  11. If female of child-bearing potential (i.e. not postmenopausal or surgically sterile), must be willing to abstain from sexual intercourse or employ an effective barrier or medical method of contraception during the study drug administration and follow-up periods. If male, must be sterile or willing to abstain from sexual intercourse or employ a barrier method of contraception during the study treatment and follow-up periods.

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 four 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 3: relapsed/refractory peripheral T-cell lymphoma (PTCL)

  1. Only PTCL patients with histologically or cytologically confirmed PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL) or anaplastic large-cell lymphoma (ALCL).
  2. 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)

  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.

Cohort 5: relapsed/refractory T-cell Prolymphocytic leukemia (T-PLL)

1. A maximum of two lines of prior therapy and no other standard therapy available with proven clinical benefit. Patients ineligible for treatment with alemtuzumab can be included.

Exclusion Criteria:

  1. Patients with any central nervous system involvement.
  2. Diagnosis of acute leukemia or any patient that has been treated with fludarabine.
  3. Allogeneic stem cell transplant patients and any patient who has relapsed within 100 days of stem cell infusion following 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 a second malignancy diagnosed within three (3) 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, arrhythmias not adequately controlled, 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.
  10. Previous cancer therapies within four (4) weeks or 5 half-lives, whichever is shorter, of dosing unless the patient has recovered to eligibility levels prior to treatment in this study.
  11. 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.
  12. 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.
  13. Patients on Valproic Acid for any indication (epilepsy, mood disorder) must be excluded from the trial or must stop using the medication and have a wash out period of 3.5 days prior to first dose of EDO-S101 (C1D1).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576496


Locations
Layout table for location information
United States, Arizona
Mayo Clinic
Phoenix, Arizona, United States, 85054
United States, Florida
Mayo Clinic Cancer Center
Jacksonville, Florida, United States, 32224
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, New York
Columbia University Medical Center
New York, New York, United States, 10019
United States, Texas
The University of Texas MDACC
Houston, Texas, United States, 77030
France
CHU de Caen
Caen, France, CS 3001
CHU Hotel Dieu
Nantes, France, 44093
Centre hospitalier Lyon Sud
Pierre Bénite, France, 69495
Italy
Institute of Hematology "L. A. Seràgnoli", University of Bologna
Bologna, Italy, 40138
National Cancer Institute, Fondazione 'G. Pascale'
Naples, Italy, I-80131
Netherlands
VU medisch centrum
Amsterdam, Netherlands, 1081 HV
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Spain
Institut Català d'Oncologia de Barcelona
Hospitalet de Llobregat, Barcelona, Spain, 08908
Hospital Universitario de Salamanca
Salamanca, Spain, 37007
Hospital Universitario Marqués de Valdecilla
Santander, Spain, 39008
Switzerland
Kantonsspital St.Gallen
St.Gallen, Switzerland, 9007
Sponsors and Collaborators
Mundipharma-EDO GmbH
Investigators
Layout table for investigator information
Principal Investigator: Owen A O'Connor, MD,PhD Columbia University

Layout table for additonal information
Responsible Party: Mundipharma-EDO GmbH
ClinicalTrials.gov Identifier: NCT02576496     History of Changes
Other Study ID Numbers: EDO-S101-1001
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: relevant patient listing data of de-identified patients may be reviewed

Keywords provided by Mundipharma-EDO GmbH:
phase 1 clinical trial
multiple myeloma
Hodgkin's lymphoma
peripheral T-cell lymphoma
cutaneous T-cell lymphoma
T-cell Prolymphocytic Leukemia
tinostamustine

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms
Hodgkin Disease
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, T-Cell, Cutaneous
Leukemia, Prolymphocytic
Leukemia, Prolymphocytic, T-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Leukemia, T-Cell