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 January 2014 by Oncopeptides AB
Sponsor:
Information provided by (Responsible Party):
Oncopeptides AB
ClinicalTrials.gov Identifier:
NCT01897714
First received: July 9, 2013
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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: 40
Study Start Date: July 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2015 (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

  Eligibility

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

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
  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 ClinicalTrials.gov identifier: NCT01897714

Contacts
Contact: Eva Nordström, MSc Pharm +46 70 634 02 11 trials@oncopeptides.se

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

No publications provided

Responsible Party: Oncopeptides AB
ClinicalTrials.gov Identifier: NCT01897714     History of Changes
Other Study ID Numbers: O-M1-12
Study First Received: July 9, 2013
Last Updated: January 13, 2014
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
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on September 22, 2014