Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2016 by Oncopeptides AB
Information provided by (Responsible Party):
Oncopeptides AB Identifier:
First received: July 9, 2013
Last updated: April 4, 2016
Last verified: April 2016
The study will explore escalating doses of melflufen in combination with dexamethasone in small groups of patients to find the maximum tolerated dose of melflufen. That dose will then be used to determine the efficacy and safety profile of melflufen in combination with dexamethasone in a larger group of patients.

Condition Intervention Phase
Relapsed and/or Relapsed-refractory Multiple Myeloma
Drug: Melflufen
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Phase I/IIa Study of the Safety and Efficacy of Melphalan-flufenamide (Melflufen) and Dexamethasone Combination for Patients With Relapsed and/or Relapsed-Refractory Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by Oncopeptides AB:

Primary Outcome Measures:
  • The primary objective of the Phase I portion of the study is to determine the Maximum Tolerated Dose (MTD) of the combination of melflufen and dexamethasone in patients with relapsed and/or relapsed-refractory Multiple Myeloma. [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
  • The primary objective of the Phase IIa part is to evaluate the objective response rate to the combination of melflufen and dexamethasone at the MTD determined in the Phase I part [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: July 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Melflufen and dexamethasone in combination
Intravenous infusion of melflufen Day 1 of 21 day cycles, in combination with 40 mg dexamethasone (oral or i.v.) day 1, 8 and 15 of the 21 day cycles.
Drug: Melflufen Drug: Dexamethasone


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Male or female, age 18 years or older
  2. Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
  3. Patient has measurable disease defined as any of the following:

    1. Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
    2. ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
    3. Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio
    4. If no monoclonal protein is detected, then ≥ 30% monoclonal bone marrow plasma cells
  4. Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
  5. Life expectancy of ≥6 months
  6. Patient has an ECOG performance status ≤ 2 (Patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible)
  7. Females of childbearing potential must have a negative serum or urine pregnancy test prior to patient registration
  8. Female patients of child bearing potential and non-vasectomized male patients agree to practice appropriate methods of birth control
  9. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
  10. The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen
  11. 12 lead ECG with QtcF interval ≤ 470 msec
  12. The following laboratory results must be met within 21 days of patient registration:

    • Absolute neutrophil count ≥ 1,000 cells/dL (1.0 x 109/L)
    • Platelet count ≥ 75,000 cells/dL (75 x 109/L)
    • Hemoglobin ≥ 8.0 g/dL
    • Total Bilirubin ≤ 1.5 x upper limit of normal
    • Renal function: Estimated creatinine clearance ≥ 45 ml/min or serum creatinine ≤ 2.5 mg/dL
    • AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN

Exclusion Criteria:

  1. Patient has evidence of mucosal or internal bleeding and/or is platelet transfusion refractory
  2. Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participation in this study
  3. Known active infection requiring parenteral or oral anti-infective treatment
  4. Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix
  5. Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration.
  6. Pregnant or breast-feeding females
  7. Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
  8. Known HIV or hepatitis B or C viral infection
  9. Patient has concurrent symptomatic amyloidosis or plasma cell leukemia
  10. POEMS syndrome
  11. Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. Biologic, novel therapy (including investigational agents in this class) or corticosteroids within 2 weeks prior to patient registration. Patient has side effects of the previous therapy > grade 1 or previous baseline.
  12. Prior peripheral stem cell transplant within 12 weeks of patient registration
  13. Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
  14. Known intolerance to steroid therapy
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01897714

Contact: Eva Nordström, MSc Pharm +46 70 634 02 11

United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Principal Investigator: Claudia E Paba Prada, MD         
United States, Michigan
Karmanos Cancer Center Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Jeffrey Zonder, MD         
United States, North Carolina
Universtity of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27514
Principal Investigator: Peter Voorhees, MD         
Vejle Hospital Recruiting
Vejle, Denmark
Principal Investigator: Torben Plesner, MD         
Turin Hospital Myeloma Unit Recruiting
Turin, Italy
Principal Investigator: Antonio Palumbo, MD         
Erasmus University Medical Center Recruiting
Rotterdam, Netherlands
Principal Investigator: Pieter Sonneveld, MD         
Sahlgrenska Hospital Recruiting
Gothenburg, Sweden
Principal Investigator: Ulf-Henrik Mellqvist, MD         
Sponsors and Collaborators
Oncopeptides AB
Study Director: Paul G Richardson, MD Dana Farber Cancer Institute, Boston MA, USA
Study Director: Johan Harmenberg, MD Oncopeptides AB, Stockholm, Sweden
Study Director: Jorge Acosta, MD Quintiles Inc, Reading, United Kingdom
  More Information

Responsible Party: Oncopeptides AB Identifier: NCT01897714     History of Changes
Other Study ID Numbers: O-M1-12 
Study First Received: July 9, 2013
Last Updated: April 4, 2016
Health Authority: United States: Food and Drug Administration
Sweden: Medical Products Agency
Denmark: Danish Health and Medicines Authority
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Vascular Diseases
BB 1101
Dexamethasone 21-phosphate
Dexamethasone acetate
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action processed this record on April 27, 2016