A Study of Melphalan Flufenamide (Melflufen) Plus Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

NCT02963493 | Completed Phase 2 Results DMC

• 1 other identifier: OP-106
• Study Type: interventional
• Target: 157
• Locations: 4 countries
• Sites: 20

Brief Summary

This study will evaluate melflufen in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma in whose disease is refractory to pomalidomide and/or an anti-CD38 monoclonal antibody. 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.

Conditions

Multiple Myeloma

Keywords

relapsed refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The overall response rate (ORR) will be estimated as the percentage of patients who achieve sCR, CR, VGPR, or PR as their best response as assessed by the investigator. Response assessed by IMWG (International myeloma working group) criteria sCR-stringent complete response: CR plus Normal FLC (free light chain) ratio and absence of clonal cells in BM CR-complete response: Negative immunofixation in serum/urine; Disappearance of soft tissue plasmacytomas; \<5% plasma cells in BM; If only FLC disease, normal FLC ratio (0.26-1.65) VGPR-very good partial response: Serum/urine M-protein detectable by immunofixation but not electrophoresis or ≥90% reduction in serum M-protein and urine M-protein \<100 mg/24 h; If only FLC disease, \>90% decrease in the difference between involved and uninvolved FLC levels PR-partial response: 50% reduction of serum M-protein and soft tissue plasmacytomas, ≥90% reduction in urinary M-protein or to \<200 mg/24 h; other special cases if M-protein unmeasurable

  Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest time to response in study recorded as 15.3 months. Longest time on treatment 35 months.

Secondary Outcomes (8)

• Progression Free Survival (PFS)

  Patients were followed until documented progression, unacceptable toxicity, patient/physician decision to withdraw or date of death, whichever came first. Longest follow-up time for PFS recorded as 37.2 months at study end.

• Duration of Response

  From date of response until the date of first documented progression or date of death from any cause, whichever came first. Longest time of response recorded as 36.2 months at study end.

• Overall Survival

  From date of first dose of study medication until the date of death from any cause, assessed up to 24 months after study drug discontinuation.

• Functional Status and Well-being: EORTC QLQ-C30

  To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

• Functional Status and Well-being: EQ-5D-3L

  To be assessed prior to dosing at Cycle 1, 2, 4, 6, 8, and End of Treatment. 23 patients were ongoing for QoL assessments at data cutoff. QoL was added in Protocol Amendment 4 beginning in Oct. 2018.

Study Arms (1)

melphalan flufenamide (melflufen) + dexamethasone

EXPERIMENTAL

Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (20 mg for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.

Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone

Interventions

Melphalan flufenamide (Melflufen) DRUG

Also known as: Pepaxto

melphalan flufenamide (melflufen) + dexamethasone

Dexamethasone DRUG

IV dexamethasone may be substituted for oral dexamethasone in the US. Oral only in Europe.

melphalan flufenamide (melflufen) + dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Oncopeptides AB: lead
• Precision For Medicine: collaborator

Study Sites (20)

Innovative Clinical Research Institute (ICRI)

Whittier, California, 90603, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

RUSH

Chicago, Illinois, 60612, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Hudson Valley Hematology Oncology

Poughkeepsie, New York, 10532, United States

Location

UPMC Hillman Cancer Insitute

Pittsburgh, Pennsylvania, 15232, United States

Location

Baylor

Dallas, Texas, 75246, United States

Location

CHU de Nantes

Nantes, 44000, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

Universita di Bolognia

Bologna, 40126, Italy

Location

Turin Hospital Myeloma Unit

Turin, 10126, Italy

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Institut Català d'Oncología (ICO) Badalona

Barcelona, 08916, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

Complejo Hospitalario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Related Publications (3)

• Richardson PG, Oriol A, Larocca A, Blade J, Cavo M, Rodriguez-Otero P, Leleu X, Nadeem O, Hiemenz JW, Hassoun H, Touzeau C, Alegre A, Paner A, Maisel C, Mazumder A, Raptis A, Moreb JS, Anderson KC, Laubach JP, Thuresson S, Thuresson M, Byrne C, Harmenberg J, Bakker NA, Mateos MV; HORIZON (OP-106) Investigators. Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma. J Clin Oncol. 2021 Mar 1;39(7):757-767. doi: 10.1200/JCO.20.02259. Epub 2020 Dec 9.

  PMID: 33296242 RESULT

• Sonneveld P, Richardson PG, Ludwig H, Dimopoulos MA, Schjesvold FH, Hajek R, Abdulhaq H, Thuresson M, Norin S, Bakker NA, Mateos MV. Benefit Versus Risk Assessment of Melflufen and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Analyses From Longer Follow-up of the OCEAN and HORIZON Studies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):687-696. doi: 10.1016/j.clml.2023.05.004. Epub 2023 May 6.

  PMID: 37355418 DERIVED

• Larocca A, Leleu X, Touzeau C, Blade J, Paner A, Mateos MV, Cavo M, Maisel C, Alegre A, Oriol A, Raptis A, Rodriguez-Otero P, Mazumder A, Laubach J, Nadeem O, Sandberg A, Orre M, Torrang A, Bakker NA, Richardson PG. Patient-reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study. Br J Haematol. 2022 Feb;196(3):639-648. doi: 10.1111/bjh.17887. Epub 2021 Oct 21.

  PMID: 34671975 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

L-melphalanyl-p-L-fluorophenylalanine ethyl ester; melflufen; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Global Clinical Project Lead
• Organization: Oncopeptides

info@oncopeptides.com

866-596-6626

Study Officials

• Johan Harmenberg, MD, PhD

  Oncopeptides AB

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: November 15, 2016
• Study Start: December 28, 2016
• Primary Completion: October 22, 2020
• Study Completion: November 16, 2021
• Last Updated: November 22, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-11

Locations

US (9); ES (7); IT (2); FR (2)