Study of Melphalan Flufenamide (Melflufen) + Dex With Bortezomib or Daratumumab in Patients With RRMM

NCT03481556 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: OP-104
• Study Type: interventional
• Target: 56
• Locations: 4 countries
• Sites: 16

Brief Summary

This is an open-label Phase 1/2a study which will enroll patients that have relapsed or relapsed-refractory multiple myeloma to combination regimens of melflufen with currently approved agents. Patients will receive either melflufen+dexamethasone+bortezomib or melflufen+dexamethasone+daratumumab.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

  Toxicity was graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 4.03. DLT criteria that apply to Regimens A and B: * Grade 3 non-hematologic toxicity preventing the administration of \> 1 dose of bortezomib or daratumumab during the 1st cycle. * Grade 4 or greater non-hematologic toxicity. * Grade 4 thrombocytopenia (platelet count \< 25,000 cells/ mm\^3) preventing the administration of \> 1 dose of bortezomib or daratumumab during the 1st cycle or with clinically significant bleeding during the 1st cycle. * Grade 4 neutropenia (ANC \< 500 cells/mm\^3), lasting more than 7 days during the 1st cycle. * Greater than 14 days' delay to meet the criteria for the start of a new cycle (Cycle 2) due to toxicity.

  Cycle 1: Day 1 to Day 28

• Phase 2: Overall Response Rate (ORR)

  ORR was defined as the percentage of participants who achieved a best confirmed response of Partial Response (PR) or better.

  Until disease progression, death or initiation of subsequent therapy (a maximum of 194.3 weeks)

Secondary Outcomes (10)

• Best Response (BR)

  Until disease progression, death or initiation of subsequent therapy (a maximum of 194.3 weeks)

• Duration of Response (DOR)

  Until disease progression, death or initiation of subsequent therapy (a maximum of 194.3 weeks)

• Time to Response (TTR)

  Until disease progression, death or initiation of subsequent therapy (a maximum of 194.3 weeks)

• Progression-Free Survival (PFS)

  Until disease progression, death or initiation of subsequent therapy (a maximum of 194.3 weeks)

• Overall Survival (OS)

  Up to 24 months following confirmed disease progression, or initiation of subsequent therapy (a maximum of 198.9 weeks)

Study Arms (2)

A (melflufen+bortezomib+dex)

EXPERIMENTAL

Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with bortezomib at 1.3mg/m² S.Q. on Days 1, 4, 8, 11 and dexamethasone 20 mg (12 mg ≥ 75 years) Days 1, 4, 8, 11 and 40 mg (20 mg ≥ 75 years) on Day 15 and 22 of each 28-day cycle.

Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone; Drug: Bortezomib

B (melflufen+daratumumab+dex)

EXPERIMENTAL

Melflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with daratumumab 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Dexamethasone p.o. 40 mg weekly (20 mg weekly for patients age ≥ 75 years).

Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone; Drug: Daratumumab

Interventions

Melphalan flufenamide (Melflufen) DRUG

Intravenous infusion

A (melflufen+bortezomib+dex); B (melflufen+daratumumab+dex)

Dexamethasone DRUG

Oral tablets

Also known as: Dex, Fortecortin, Decadron

A (melflufen+bortezomib+dex); B (melflufen+daratumumab+dex)

Bortezomib DRUG

Subcutaneous administration

Also known as: Velcade

A (melflufen+bortezomib+dex)

Daratumumab DRUG

Intravenous infusion

Also known as: Dara, Darzalex

B (melflufen+daratumumab+dex)

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 in need of treatment at time of screening
• One to four prior lines of therapy
• Measurable disease defined as any of the following:
• Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
• ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
• Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
• Life expectancy of ≥ 6 months
• ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor)
• Patient is a female of childbearing potential (FCBP)\* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control
• Ability to understand the purpose and risks of the study and provide signed and dated informed consent
• lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
• Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1:
• Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy)
• Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without required transfusions during the 10 days prior to initiation of therapy)

You may not qualify if:

• Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)
• Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by \> 10,000 cells/mm3 after transfusion of an appropriate dose of platelets)
• 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. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months)
• Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy
• Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
• Pregnant or breast-feeding females
• Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
• Known human immunodeficiency virus 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 and skin changes)
• Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. Other investigational therapies and monoclonal antibodies (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (q.d.) or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy
• Residual side effects to previous therapy \> Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted)
• Prior peripheral stem cell transplant within 12 weeks of initiation of therapy
• Prior allogeneic stem cell transplantation with active graft-versus-host- disease
• Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy)

Sponsors & Collaborators

• Oncopeptides AB: lead

Study Sites (16)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Fakultní nemocnice Brno

Brno, Czechia

Location

Fakultní nemocnice Hradec Králové

Hradec Králové, Czechia

Location

Fakultní nemocnice Ostrava

Ostrava, Czechia

Location

Všeobecná fakultní nemocnice

Prague, Czechia

Location

Hôpital Morvan

Brest, France

Location

Centre Jean Bernard - Clinique Victor Hugo

Le Mans, France

Location

Hôpital privé du Confluent

Nantes, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Centre Hospitalier Universitaire Institut Gustave Roussy

Villejuif, France

Location

Hospital Universitai Germans Trias i Pujol

Badalona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Complejo Hospitalario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Marques de Valdecilla

Santander, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

L-melphalanyl-p-L-fluorophenylalanine ethyl ester; melflufen; Dexamethasone; dexamethasone acetate; Calcium Dobesilate; Bortezomib; daratumumab; darlin protein, Dictyostelium

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; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

On 04 November 2021, the study was terminated early during Phase 2a.

Results Point of Contact

• Title: VP Chief Operating Officer
• Organization: Oncopeptides AB

trials@oncopeptides.com

+46 8 615 20 40

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2018
• First Posted: March 29, 2018
• Study Start: April 12, 2018
• Primary Completion: February 2, 2022
• Study Completion: February 2, 2022
• Last Updated: December 19, 2022
• Results First Posted: December 19, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); CZ (4); FR (5); ES (5)