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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02576496
Recruitment Status : Recruiting
First Posted : October 15, 2015
Last Update Posted : January 10, 2019
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.

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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

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

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 identifier (NCT number): NCT02576496

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United States, Arizona
Mayo Clinic Recruiting
Phoenix, Arizona, United States, 85054
Contact: Leif Bergsagel, MD    480-301-8335   
Principal Investigator: Leif Bergsagel, MD         
United States, Florida
Mayo Clinic Cancer Center Recruiting
Jacksonville, Florida, United States, 32224
Contact: Han W Tun, MD    904-953-7290   
Contact: Kathleen M Burke, RN    904 953 6174   
Principal Investigator: Han W. Tun, MD         
United States, Minnesota
Mayo Clinic Cancer Center Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Wei Ding, MD    507-284-2511   
Contact: Joeliann M Quarve    507-538-4846   
Principal Investigator: Wei Ding, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10019
Contact: Owen A O'Connor, MD,PhD    212-326-5720   
Contact: Freddy Laffredo    212-326-5733   
United States, Texas
The University of Texas MDACC Not yet recruiting
Houston, Texas, United States, 77030
Contact: Gautam Borthakur, MD    713-563-1586   
Contact: Carol Bivins    713-794-4460   
Principal Investigator: Gautam Borthakur, MD         
CHU de Caen Not yet recruiting
Caen, France, CS 3001
Contact: Ghandi L Damaj, MD    00 33 231 06 25 36   
Contact: Emilie Marin    00 33 231 27 20 72   
Principal Investigator: Ghandi L Damaj, MD         
CHU Hotel Dieu Not yet recruiting
Nantes, France, 44093
Contact: Philippe Moreau, MD    00 33 240 08 32 71   
Principal Investigator: Philippe Moreau, MD         
Centre hospitalier Lyon Sud Not yet recruiting
Pierre Bénite, France, 69495
Contact: Gilles Salles, MD    00 33 478 86 43 07   
Contact: Virginie Tronchon    00 33 478 84 43 35   
Principal Investigator: Gilles Salles, MD         
Institute of Hematology "L. A. Seràgnoli", University of Bologna Recruiting
Bologna, Italy, 40138
Contact: Luigi Zinzani, MD    +39 0512143680   
Principal Investigator: Luigi Zinzani, MD         
National Cancer Institute, Fondazione 'G. Pascale' Recruiting
Naples, Italy, I-80131
Contact: Antonio Pinto, MD    +39 081 5903 382   
Principal Investigator: Antonio Pinto, MD         
VU medisch centrum Not yet recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Josée Zijlstra, MD    +31 20 4442604   
Contact: Maaike Leidekker    +31 20 4442639   
Principal Investigator: Josée Zijlstra, MD         
Erasmus MC Not yet recruiting
Rotterdam, Netherlands, 3015 GD
Contact: Pieternella Lugtenburg, MD    +31 10 7033123   
Principal Investigator: Pieternella Lugtenburg, MD         
Institut Català d'Oncologia de Barcelona Not yet recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08908
Contact: Ana S Balari, MD    +34 93 260 72 10   
Principal Investigator: Ana S Balari, MD         
Hospital Universitario de Salamanca Not yet recruiting
Salamanca, Spain, 37007
Contact: Maria V Mateos, MD    +34 678438203   
Principal Investigator: Maria V Mateos, MD         
Hospital Universitario Marqués de Valdecilla Not yet recruiting
Santander, Spain, 39008
Contact: Enrique Ocio, MD    +34 649-391848   
Principal Investigator: Enrique Ocio, MD         
Kantonsspital St.Gallen Recruiting
St.Gallen, Switzerland, 9007
Contact: Christoph Driessen, MD    41 71 494 11 62   
Principal Investigator: Christoph Driessen, MD         
Sponsors and Collaborators
Mundipharma-EDO GmbH
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Principal Investigator: Owen A O'Connor, MD,PhD Columbia University

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Responsible Party: Mundipharma-EDO GmbH Identifier: NCT02576496     History of Changes
Other Study ID Numbers: EDO-S101-1001
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: December 2018
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

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
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
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, T-Cell