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Trial record 1 of 1 for:    NCT04115956
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A Clinical Study of Melphalan Flufenamide (Melflufen) and Dexamethasone for Patients With Immunoglobulin Light Chain (AL) Amyloidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT04115956
Recruitment Status : Active, not recruiting
First Posted : October 4, 2019
Last Update Posted : July 12, 2021
PRA Health Sciences
Information provided by (Responsible Party):
Oncopeptides AB

Brief Summary:

This is a phase 1/2 open label study of melphalan flufenamide (melflufen) in combination with dexamethasone for participants with Al amyloidosis following at least one prior line of therapy. Melflufen will be administered on Day 1 of each 28-day cycle in combination with dexamethasone on days 1 and 2.

In both phases, treatment of each individual participant will continue for up to 8 cycles or until any stopping events occur.

Approximately 46 participants will be enrolled.

Condition or disease Intervention/treatment Phase
AL Amyloidosis Drug: Melphalan-Flufenamide (Melflufen) Drug: Dexamethasone Phase 1 Phase 2

Detailed Description:

This is a clinical trial of melphalan flufenamide (melflufen), a peptide-conjugated alkylator which belongs to an novel class of drugs called peptidase-enhanced compounds, and targets the transformation process of tumor cells with a unique mechanism of action, as potential treatment option of AL amyloidosis.

AL amyloidosis is a rare progressive disease caused by proteotoxic light chain protein produced by small plasma cell clone. This plasma cell dyscrasia is characterized by monoclonal plasma cell's excessive production of monoclonal immunoglobulin light-chains that tends to misfold and subsequently deposit as amyloid fibrils in visceral organs. The plasma cell dyscrasia in AL amyloidosis is similar to that in multiple myeloma (MM) and therapies that are effective in MM are often used to treat AL amyloidosis.

Melphalan flufenamide is currently been evaluated in several ongoing clinical trials in patients with multiple myeloma, with observed efficacy. There are currently no therapies approved for treatment of AL amyloidosis and based on the efficacy of melphalan flufenamide and the demonstrated efficacy of melphalan (and other alkylators), it is anticipated that patients with AL amyloidosis may receive benefit from treatment with melphalan flufenamide.

This study consist of a screening period (up to 28 days), a treatment period (up to 8 cycles) and a follow-up period (up to 24 months).

Phase 1: Approximately 8-30 participants will be screened to achieve 7-23 enrolled participants.

Phase 2: Approximately 30 participants will be screened to achieve 23 enrolled participants.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Melflufen + Dexamethasone
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 1/2 Study of Melflufen and Dexamethasone for Patients With AL Amyloidosis Following at Least One Prior Line of Therapy
Actual Study Start Date : August 6, 2020
Estimated Primary Completion Date : February 2023
Estimated Study Completion Date : April 2024

Arm Intervention/treatment
Experimental: Melflufen and dexamethasone in combination
Intravenous infusion of melflufen Day 1 of 28 day cycles, in combination of dexamethasone on Days 1 and 2 of each 28-day cycle.
Drug: Melphalan-Flufenamide (Melflufen)
Treatment consist of i.v. melflufen on Day 1 of each 28-day cycle.

Drug: Dexamethasone
Dexamethasone 40 mg (20 mg at investigator's discretion) administered on Days 1 and 2 of each 28-day cycle.
Other Name: Dexamethason JENAPHARM

Primary Outcome Measures :
  1. The primary objective in Phase 1 is to explore safety and tolerability of melflufen [ Time Frame: During phase 1 for up to 8 cycles of treatment of 28 days each (approx. up to 8 months) ]


    • Frequency and grade of Adverse Events. The maximum grade for each type of AE will be recorded for each participant and frequency tables will be presented and reviewed to determine patterns
    • Laboratory values (laboratory abnormalities) for hematology, coagulation, blood chemistry, urinalysis

  2. The primary objective in Phase 1 is to identify recommended Phase 2 dose (RP2D) [ Time Frame: During phase 1 for up to 8 cycles of 28 days each (approx. up to 8 months) ]
    Endpoint: Dose-Limiting Toxicity (DLT) during Cycle 1 up to maximum dose of melflufen of 40 mg. A DLT event is defined as thrombocytopenia, neutropenia, non-hematologic toxicity and/or inability to receive Cycle 2 Day 1 dose within 14 days from planned Cycle 2 Day 2 due to continued melflufen-related toxicity from Cycle 1.

  3. The primary endpoint in Phase 2 is to evaluate the hematologic overall response rate (ORR) after 4 cycles at the RP2D determined in Phase 1 [ Time Frame: During phase 2 after 4 cycles of treatment ( approx. 4 months) ]
    The proportion of participants who achieve a hematologic Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR)

Secondary Outcome Measures :
  1. To assess pharmacokinetic profile of melflufen in this patient population [ Time Frame: At Cycle 1 Day 1 and Cycle 2 Day 1 at time points 5-10 minutes, 1-2 hours and 3-8 hours after end of infusion. Each cycle length is 28 days. ]
    Melphalan plasma concentration post melflufen administration at 3 time points

  2. To assess best hematologic response [ Time Frame: Throughout the study treatment of up to 8 cycles of 28 days each (approx. 8 months) per patient ]
    Proportion of patients with each outcome (Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) or Progressive Disease (PD))

  3. To assess the duration of hematologic response [ Time Frame: Throughout the study treatment period of up to 8 cycles of 28 days each (approx 8 months) per patient ]
    Median time (Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR) or Progressive Disease (PD))

  4. To assess the proportion of organ system responses [ Time Frame: Throughout the study treatment period of up to 8 cycles of 28 days each (approx 8 months) per patient ]
    Proportion of participants with kidney, cardiac or liver response, respectively

  5. To assess duration of organ system responses [ Time Frame: Throughout the study treatment period of up to 8 cycles (approx 8 months) per patient ]
    Duration of organ responses separately for each organ

  6. To assess hematologic ORR (overall response rate) [ Time Frame: During phase 1 for up to 8 cycles of treatment of 28 days each (approx. up to 8 months) ]
    Proportion of participants who achieve a hematologic CR, VGPR or PR

  7. To assess time to next AL amyloidosis treatment [ Time Frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and 24 months of follow up ]
    Time to next AL amyloidosis treatment

  8. To assess Overall Survival (OS) [ Time Frame: Throughout the study, covering up to 8 cycles (approx. 8 months) of treatment and up to 24 months of follow up ]
    Overall survival

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria: (For full list of inclusion criteria, see study protocol)

  • Male or female, age 18 years or older at the time of signing the informed consent
  • Proven histochemical diagnosis of AL amyloidosis based on tissue specimens with Congo red staining
  • At least one prior line of therapy, defined as either one non-transplant regimen, one ASCT (autologous stem cell transplantation), or one regimen of induction therapy followed by a single ASCT. No more that 4 cycles of melphalan containing chemotherapy is allowed.
  • Measurable hematologic disease
  • Objectively measurable organ amyloid involvment
  • ECOG performance status ≤ 2 (ECOG = Eastern cooperative oncology group)
  • Women of child bearing potential must have a negative serum or urine pregnancy test
  • Less than 30% plasma cells in bone marrow aspirate or biopsy
  • Acceptable laboratory results met (absolute neutrophil count (ANC), platelet count, hemoglobin, total bilirubin,alkaline phosphatase, AST (aspartate aminotransferase) and ALT (alanine aminotransferase), renal function)
  • Male participant agrees to use contraception during treatment and 90 days after last dose of melflufen

Exclusion Criteria: (For full list of exclusion criteria, see study protocol)

  • Amyloidosis due to known mutations of the transthyretin gene or presence of another non-AL amyloidosis
  • Evidence of gastro-intestinal bleeding
  • Cardiac risk stage 3
  • Low platelets value with evidence of mucosal or internal bleeding
  • Medical documented cardiac syncope, NYHA Class 3 or 4 congestive heart failure, myocardial infarction, unstable angina pectoris, clinically significant ventricular arrhythmias (NYHA=New York Heart Association Functional Classification)
  • Clinically significant finding on 24 h Holter recording
  • Severe orthostatic hypotension
  • Clinically significant factor X deficiency
  • Clinically significant autonomic disease
  • Any medical condition that would impose excessive risk to the patient
  • Serious psychiatric illness, active alcoholism or drug addiction that may hinder or confuse compliance
  • Known HIV or active hepatitis B or C viral infections
  • Previous cytotoxic therapies, including cytotoxic investigational agents within 3 weeks prior to start of study treatment. Monoclonal antibodies within 4 weeks. Concomitant immunotherapy, investigational therapy and anticoagulation therapy are not permitted
  • Prior autologous or allogenic stem cell transplant within 12 weeks of initiation of therapy
  • Prior allogeneic stem cell transplant with active graft-host-disease
  • Prior major surgical procedure or radiation therapy within 4 weeks of the first dose of study treatment

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 identifier (NCT number): NCT04115956

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United States, Massachusetts
Boston University Medical Center
Boston, Massachusetts, United States, 02111
Fakultní Nemocnice Ostrava
Ostrava - Poruba, Czechia, 70852
Centre Hospitalier Universitaire de Limoges
Limoges, France, 87000
Universitätsklinikum Heidelberg
Heidelberg, Germany, 69120
Alexandra General Hospital of Athens
Athen, Greece, 11528
Hadassah University Hospital Ein Kerem
Jerusalem, Israel, 9112001
Fondazione IRCCS Policlinico San Matteo
Pavia, Italy, 27100
Oslo University Hospital - Rikshospitalet
Oslo, Norway, 0372
Instytut Hematologii i Transfuzjologii
Warszawa, Poland, 00791
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom, NW1 2BU
Sponsors and Collaborators
Oncopeptides AB
PRA Health Sciences
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Principal Investigator: Giovanni Palladini, MD University Hospital San Matteo in Pavia
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Responsible Party: Oncopeptides AB Identifier: NCT04115956    
Other Study ID Numbers: OP201
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: July 12, 2021
Last Verified: July 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Immunoglobulin Light-chain Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors