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

Study Description

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Brief Summary:

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

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	75 participants
Intervention Model:	Single Group Assignment
Masking:	None (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
Study Start Date :	July 2013
Actual Primary Completion Date :	December 2017
Estimated Study Completion Date :	October 2019

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. 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 ]
2. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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 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

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Locations

United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Michigan
Karmanos Cancer Center
Detroit, Michigan, United States, 48201
United States, North Carolina
Universtity of North Carolina
Chapel Hill, North Carolina, United States, 27514
Denmark
Vejle Hospital
Vejle, Denmark
Italy
Turin Hospital Myeloma Unit
Turin, Italy
Netherlands
Erasmus University Medical Center
Rotterdam, Netherlands
Sweden
Sahlgrenska Hospital
Gothenburg, Sweden

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

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Oncopeptides AB
ClinicalTrials.gov Identifier:	NCT01897714 History of Changes
Other Study ID Numbers:	O-M1-12
First Posted:	July 12, 2013
Last Update Posted:	March 21, 2018
Last Verified:	March 2018

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; BB 1101; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Protease Inhibitors; Enzyme Inhibitors