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A Study of Melflufen in Combination With Dexamethasone in Relapsed Refractory Multiple Myeloma Patients (HORIZON)

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: NCT02963493
Recruitment Status : Recruiting
First Posted : November 15, 2016
Last Update Posted : September 2, 2019
Precision for Medicine, Oncology and Rare Disease
Information provided by (Responsible Party):
Oncopeptides AB

Brief Summary:
This study will evaluate melflufen in combination with dexamethasone in the treatment of relapsed refractory multiple myeloma in adult patients with disease refractory to pomalidomide and/or daratumumab. All patients in the study will be treated with melflufen on Day 1 and dexamethasone on Days 1, 8, 15 and 22 of each 28-day cycle.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Melflufen Drug: Dexamethasone Phase 2

Detailed Description:
Melflufen is designed for targeted delivery of alkylating moieties to tumor cells. In contrast to other alkylating agents that are hydrophilic, the lipophilicity of melflufen leads to rapid and extensive distribution into tissues and cells. Inside cells, melflufen may directly bind DNA or is readily metabolized by intracellular peptidases into the well-known antitumor compound melphalan, or by esterases into des-ethylmelflufen, which also has alkylating properties. Due to the high activity of peptidases and esterases in human tumor cells, the formation of melflufen's metabolites is rapid in these cells with subsequent inflow of more melflufen. Since des-ethylmelflufen and melphalan are relatively hydrophilic, there is a possibility for intracellular trapping of these alkylators.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Open-Label, Phase 2 Study of Melflufen in Combination With Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Pomalidomide and/or Daratumumab
Actual Study Start Date : December 2016
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : November 2021

Arm Intervention/treatment
Experimental: melflufen + dexamethasone
Melflufen 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.
Drug: Melflufen
Drug: Dexamethasone

Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    The overall response rate (ORR) will be estimated as the proportion of patients in each group who achieve sCR, CR, VGPR, or PR as their best response.

Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: From date of first dose of study medication until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Time from start of treatment to either progression or death, whichever comes first

  2. Duration of Response [ Time Frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Time from first response to progression

  3. Overall Survival [ Time Frame: From date of first dose of study medication until the date of death from any cause, assessed up to 36 months ]
    Time from start of treatment to death

  4. Functional status and well-being: EORTC QLQ-C30 [ Time Frame: Through study completion, an average of 6 months ]
    Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30

  5. Functional status and well-being: EQ-5D-3L [ Time Frame: Through study completion, an average of 6 months ]
    Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L

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.

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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:

  • Male or female, age 18 years or older
  • A prior diagnosis of multiple myeloma with documented disease progression
  • Measurable disease based on either of a) serum monoclonal protein by protein electrophoresis (SPEP), b) monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP), and/or c) serum immunoglobulin free light chain combined with abnormal serum immunoglobulin kappa to lambda free light chain ratio
  • A minimum of 2 prior lines of therapy including an IMiD and a PI and is refractory to pomalidomide and/or daratumumab
  • Life expectancy of ≥ 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Female of child bearing potential (FCBP) and non-vasectomized male agree to practice appropriate methods of birth control
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
  • 12-lead ECG with QTc interval within defined limit
  • Acceptable laboratory results during screening and prior to first study drug administration of the following parameters: absolute neutrophil count (ANC), platelet count, hemoglobin, total bilirubin, aspartate transaminase (AST/SGOT) and alanine transaminase (ALT/SGPT), renal function based on estimated creatinine clearance
  • Must have, or accept to have, an acceptable central catheter for infusion of melflufen

Exclusion Criteria:

  • Evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
  • Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study
  • Known active infection requiring parenteral or oral anti-infective treatment within defined period
  • Primary refractory disease
  • Other malignancy diagnosed or requiring treatment within the defined period with specific exceptions
  • Pregnant or breast-feeding females
  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
  • Known HIV or active hepatitis B or C viral infection
  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes]
  • Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within defined values prior to start of study treatment
  • Residual side effects to previous therapy over specific grade prior to initiation of therapy
  • Prior autologous or allogeneic stem cell transplant within defined period of initiation of therapy
  • Prior allogeneic stem cell transplant with active graft-versus-host- disease (GVHD).
  • Prior major surgical procedure or radiation therapy within specified period of the first dose of study treatment (with defined exception).
  • Known intolerance to steroid therapy

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): NCT02963493

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Contact: Eva Nordstrom, PhD +46 706340211
Contact: Jakob Lindberg, MLic, BA +46 705695471

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United States, California
Innovative Clinical Research Institute (ICRI) Recruiting
Whittier, California, United States, 90603
Principal Investigator: Amitabha Mazumder, MD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Principal Investigator: John Hiemenz, MD         
United States, Illinois
RUSH Recruiting
Chicago, Illinois, United States, 60612
Principal Investigator: Agne Paner, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Paul Richardson, MD         
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Jeffrey Zonder         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Principal Investigator: Hani Hassoun, MD         
Hudson Valley Hematology Oncology Recruiting
Poughkeepsie, New York, United States, 10532
Principal Investigator: Ramamohana Kancherla, MD         
United States, Ohio
Gabrail Cancer Research Center Withdrawn
Canton, Ohio, United States, 44718
United States, Pennsylvania
UPMC Hillman Cancer Insitute Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Principal Investigator: Anastasios Raptis, MD         
United States, Texas
Baylor Recruiting
Dallas, Texas, United States, 75246
Principal Investigator: Christopher Maisel, MD         
Scott and White Memorial Hospital Withdrawn
Temple, Texas, United States, 76508
CHU de Nantes Recruiting
Nantes, France, 44000
Principal Investigator: Cyrille Touzeau, MD         
CHU de Poitiers Recruiting
Poitiers, France, 86021
Principal Investigator: Xavier Leleu, MD         
Universita di Bolognia Recruiting
Bologna, Italy, 40126
Principal Investigator: Michele Cavo, MD         
Turin Hospital Myeloma Unit Recruiting
Turin, Italy, 10126
Principal Investigator: Alessandra Larocca, MD         
Hospital Clinic i Provincial de Barcelona Recruiting
Barcelona, Spain, 08036
Principal Investigator: Joan Bladé Creixenti, MD         
Institut Català d'Oncología (ICO) Badalona Recruiting
Barcelona, Spain, 08916
Principal Investigator: Albert Oriol Rocafiguera         
Hospital Universitario de La Princesa Recruiting
Madrid, Spain, 28006
Principal Investigator: Adrián Alegre Amor, MD         
Hospital Universitario Fundación Jiménez Díaz Active, not recruiting
Madrid, Spain, 28040
Clínica Universidad de Navarra Recruiting
Pamplona, Spain, 31008
Principal Investigator: Paula Rodríguez Otero, MD         
Complejo Hospitalario de Salamanca Recruiting
Salamanca, Spain, 37007
Principal Investigator: Maria Victoria Mateos Manteca, MD         
Hospital Universitario Doctor Peset Active, not recruiting
Valencia, Spain, 46017
Sponsors and Collaborators
Oncopeptides AB
Precision for Medicine, Oncology and Rare Disease

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Responsible Party: Oncopeptides AB Identifier: NCT02963493     History of Changes
Other Study ID Numbers: OP-106
First Posted: November 15, 2016    Key Record Dates
Last Update Posted: September 2, 2019
Last Verified: November 2018
Keywords provided by Oncopeptides AB:
relapsed refractory multiple myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors