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

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ClinicalTrials.gov Identifier: NCT02963493
Recruitment Status : Recruiting
First Posted : November 15, 2016
Last Update Posted : November 27, 2018
Sponsor:
Collaborator:
Precision Oncology
Information provided by (Responsible Party):
Oncopeptides AB

Tracking Information
First Submitted Date  ICMJE October 18, 2016
First Posted Date  ICMJE November 15, 2016
Last Update Posted Date November 27, 2018
Actual Study Start Date  ICMJE December 2016
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2018)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 10, 2016)
Overall Response Rate (ORR) [ Time Frame: At completion of treatment for all patients, approximately 2 years. ]
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.
Change History Complete list of historical versions of study NCT02963493 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2018)
  • 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
  • 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
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2016)
  • Progression Free Survival (PFS) [ Time Frame: At time of progression, or, if no progression, 24 months after completion of treatment ]
  • Duration of Response [ Time Frame: At time of progression, or, if no progression, 24 months after completion of treatment ]
  • Overall Survival [ Time Frame: At time of death, or, if no death, 24 months after completion of treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Melflufen in Combination With Dexamethasone in Relapsed Refractory Multiple Myeloma Patients
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Melflufen
  • Drug: Dexamethasone
Study Arms  ICMJE 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.
Interventions:
  • Drug: Melflufen
  • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 25, 2018)
150
Original Estimated Enrollment  ICMJE
 (submitted: November 10, 2016)
78
Estimated Study Completion Date  ICMJE November 2021
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Eva Nordstrom, PhD +46 706340211 eva.nordstrom@oncopetides.se
Contact: Jakob Lindberg, MLic, BA +46 705695471 jakob.lindberg@oncopeptides.se
Listed Location Countries  ICMJE Spain,   France,   Italy,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02963493
Other Study ID Numbers  ICMJE OP-106
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Oncopeptides AB
Study Sponsor  ICMJE Oncopeptides AB
Collaborators  ICMJE Precision Oncology
Investigators  ICMJE Not Provided
PRS Account Oncopeptides AB
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP