Trial record 1 of 1 for:
NCT02963493
A Study of Melphalan Flufenamide (Melflufen) in Combination With Dexamethasone in Relapsed Refractory Multiple Myeloma Patients (HORIZON)
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| ClinicalTrials.gov Identifier: NCT02963493 |
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Recruitment Status :
Active, not recruiting
First Posted : November 15, 2016
Last Update Posted : July 7, 2020
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Sponsor:
Oncopeptides AB
Collaborator:
Precision for Medicine, Oncology and Rare Disease
Information provided by (Responsible Party):
Oncopeptides AB
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Brief Summary:
This study will evaluate melflufen in combination with dexamethasone in the treatment of relapsed refractory multiple myeloma in adult patients with disease 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Melphalan flufenamide (Melflufen) Drug: Dexamethasone | Phase 2 |
Melphalan flufenamide (melflufen) is a peptide-drug conjugate that rapidly delivers an alkylating payload into tumor cells. Peptidases are expressed in several cancers, including solid tumors and hematologic malignancies. Melphalan flufenamide is rapidly taken up by myeloma cells due to its high lipophilicity. Once inside the myeloma cell, the activity of melphalan flufenamide is determined by its immediate cleavage by peptidases into hydrophilic alkylator payloads that are entrapped. Melphalan flufenamide is 50-fold more potent than melphalan in myeloma cells in vitro due to increased intracellular alkylator concentration. It rapidly induces irreversible DNA damage leading to apoptosis of myeloma cells. Melphalan flufenamide displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, in vitro. Melphalan flufenamide also has demonstrated inhibition of angiogenesis and DNA damage with a lack of functional DNA repair in preclinical studies.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 157 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Single Arm, Open-Label, Phase 2 Study of Melflufen in Combination With Dexamethasone in Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Pomalidomide and/or an Anti-CD38 Monoclonal Antibody |
| Actual Study Start Date : | December 28, 2016 |
| Estimated Primary Completion Date : | September 2021 |
| Estimated Study Completion Date : | September 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: melphalan flufenamide (melflufen) + dexamethasone
Melphalan flufenamide (melflufen) 40 mg Day 1 and dexamethasone 40 mg (reduced dose for patients 75 years or older) on Days 1, 8, 15 and 22 of each 28-day cycle.
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Drug: Melphalan flufenamide (Melflufen) Drug: Dexamethasone |
Primary Outcome Measures :
- Overall Response Rate (ORR) [ Time Frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]The overall response rate (ORR) will be estimated as the proportion of patients who achieve sCR, CR, VGPR, or PR as their best response.
Secondary Outcome Measures :
- Progression Free Survival (PFS) [ Time Frame: From date of first dose of study medication until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]Time from start of treatment to either progression or death, whichever comes first
- Duration of Response [ Time Frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]Time from first response to progression
- Overall Survival [ Time Frame: From date of first dose of study medication until the date of death from any cause, assessed up to 36 months ]Time from start of treatment to death
- Functional status and well-being: EORTC QLQ-C30 [ Time Frame: Through study completion, assessed up til 24 months. ]Change from baseline in Patient Reported Outcome questionnaire EORTC QLQ-C30
- Functional status and well-being: EQ-5D-3L [ Time Frame: Through study completion, assessed up til 24 months. ]Change from baseline in Patient Reported Outcome questionnaire EQ-5D-3L
- Clinical Benefit Rate [ Time Frame: From date of response until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]The clinical benefit rate (CBR) will be estimated as the proportion of patients who achieve sCR, CR, VGPR, PR, or MR as their best response.
- Time to response [ Time Frame: From start of treatment to first confirmed response, an estimated average of 6 months. ]Duration from start of treatment to the first occurrence of a confirmed response of PR or better.
- Time to progression [ Time Frame: From start of treatment to first evidence of disease progression, assessed up to 24 months. ]Duration from start of treatment to first evidence of disease progression.
- Safety and tolerability [ Time Frame: From start of study treatment to at least 30 days after last dose of study medication, an estimated average of up to 12 months. ]Frequency and grade of adverse events
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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
- 12-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
Exclusion Criteria:
- 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).
- Known intolerance to steroid therapy
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02963493
Locations
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Sponsors and Collaborators
Oncopeptides AB
Precision for Medicine, Oncology and Rare Disease
| Responsible Party: | Oncopeptides AB |
| ClinicalTrials.gov Identifier: | NCT02963493 |
| Other Study ID Numbers: |
OP-106 |
| First Posted: | November 15, 2016 Key Record Dates |
| Last Update Posted: | July 7, 2020 |
| Last Verified: | July 2020 |
Keywords provided by Oncopeptides AB:
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relapsed refractory multiple myeloma |
Additional relevant MeSH terms:
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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 |
Melphalan 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 Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |