RRMMPhase 2PORTNCT04412707
A PK, Safety and Tolerability Study of Peripheral and Central Infusion of Melflufen in RRMM Patients
A Phase 2 study testing Melphalan and Dexamethasone in people with RRMM, run by Oncopeptides AB at 10 sites in 5 countries.
Trial summary
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing safety and tolerability and efficacy of peripheral and central intravenous administration of melflufen in patients with RRMM. It is an international study, enrolling patients in US and Europe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RRMM
- What is being tested?
- Melphalan and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 4 Aug 2020to 10 Jan 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age 18 years or older
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
- A prior diagnosis of multiple myeloma (MM) with documented disease progression in need of treatment at time of screening;
- Measurable disease defined as any of the following:
- Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
- ≥ 200 mg/24hr of monoclonal protein in the 24hour urine collection by electrophoresis (UPEP)
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- Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain (FLC) ratio
- Received at least 2 prior lines of therapy and is refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI). The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10 and Appendix 8.
- Adequate peripheral arm veins for repeated intravenous infusions
- Life expectancy of ≥ 6 months;
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2, see Appendix 6. Patients with ECOG performance status > 2 solely based on bone pain secondary to MM may be eligible following consultation and approval of medical monitor;
- 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec, see Appendix 11;
- Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study treatment 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 study treatment)
- Platelet count ≥ 75,000 cells/ mm³ (75 x 10⁹/L) (without transfusions during the 10 days prior to initiation of therapy)
- Hemoglobin ≥ 8.0 g/dL (Red blood cell [RBC] transfusions are permitted)
- Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), except patients diagnosed with Gilbert's syndrome that have been reviewed and approved by the Medical Monitor
- Aspartate aminotransferase (AST) serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) serum glutamic-pyruvic transaminase (SGPT) ≤ 3.0 x ULN
- Renal function: Estimated glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula of ≥ 45 mL/min, see Appendix 12.
- Must have or be willing to have an acceptable central catheter (Port a Cath, peripherally inserted central catheter [PICC] line, or central venous catheter [CVC]) and a PVC;
- a) Male patients: A male patient is eligible if he agrees to use contraception as detailed in Appendix 4 of this protocol during the treatment period and for at least 3 months after the last dose of study treatment and refrains from donating sperm during this period b) Female patients: A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: I. Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 or II. A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the treatment period and for at least 28 days after the last dose of study treatment
Who cannot join
- Primary refractory disease (i.e. never responded with at least minimal response [MR] to any prior therapy);
- Evidence of mucosal and/or internal bleeding or platelet transfusion refractory (platelet count fails to increase by > 10,000 cells/mm³ after a 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 cardiac conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months);
- Known active infection that is uncontrolled or has required intravenous systemic therapy within 14 days of randomization. Patients that have required oral anti-infective treatment within 14 days of randomization should be discussed with the Medical Monitor;
- 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;
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- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation;
- Human immunodeficiency virus (HIV) or active hepatitis B or C viral infection;
- Concurrent known or suspected amyloidosis or plasma cell leukemia;
- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes);
- Known central nervous system (CNS) or meningeal involvement of myeloma
- Any of the following treatments, within the specified timeframe
- Previous cytotoxic therapies, including cytotoxic investigational agents, for MM 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 within 4 weeks of initiation of therapy.
- Prednisone up to but no more than 10 mg orally 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.
- Other washout times may be considered following consultation with the medical monitor.
- 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 stem cell transplant (autologous and/or allogenic) within 6 months 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 the initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy);
- Known intolerance to the required dose and schedule of steroid therapy, as determined by the investigator;
- Known hypersensitivity reaction to melphalan, melflufen or its excipients
- Prior treatment with melflufen
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Ukraine3 sites
Public Non-Profit Enterprise "City Clinical Hospital #4" under Dnipro City Council, Regional Hematology Center
Dnipro
Public Non-Profit Enterprise "Kyiv City Clinical Hospital #9" under the Executive Body of Kyiv City Council, Hematology Department #1
Kyiv
Institute of Blood Pathology and Transfusion Medicine, Department of Hematology with Laboratory Group
Lviv
Bulgaria2 sites
Specialized Hospital for Active Treatment of Hematological Diseases, Sofia
Sofia
Multiprofile Hospital for Active Treatment "Sveta Marina", Varna
Varna
Czechia2 sites
University Hospital Brno, Clinic of Internal Medicine - Hematology and Oncology
Brno, 62500
University Hospital Olomouc, Clinic of Hemato-Oncology
Olomouc, 77900
Hungary2 sites
Central Hospital of Southern Pest National Institute of Hematology and Infectious Diseases, Department of Hematology and Stem Cell Transplantation
Budapest
Semmelweis University, 3rd Department of Internal Medicine
Budapest
United States1 site
The Oncology Institute of Hope & Innovation - Glendale
Glendale, California, 91204
About this study
Official title: A Randomized, Two-period, Cross-over, Phase 2 Study, Comparing Pharmacokinetics, and Assessing Safety and Tolerability of Peripheral and Central i.v. Administration of Melphalan Flufenamide (Melflufen) in RRMM Patients
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing safety and tolerability and efficacy of peripheral and central intravenous administration of melflufen in patients with RRMM. It is an international study, enrolling patients in US and Europe. The study will enroll patients following at least 2 lines of prior therapy.
- Conditions
- RRMM
- Being tested
- Melphalan, Dexamethasone
- Keywords
- central intravenous administration, peripheral intravenous administration, central venous catheter (CVC), peripheral venous catheter (PVC)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelphalanDrug
Also called melflufen flufenamide
Peripheral versus central administration
DexamethasoneDrug
Oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Active comparator | Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC). Receives: Drug: Melphalan; Drug: Dexamethasone |
| Arm B | Active comparator | Melflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC. Receives: Drug: Melphalan; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Plasma Concentration for Melphalan
To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.
Measured: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.
Measured: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen
Measured: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration
Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.
Measured: 15 minutes and 4 hours after peripheral intravenous administration, pre- and post-infusion on Day 1 and Day 8
Secondary outcomes (16)
Peak Plasma Concentration for Melflufen and Desethyl-melflufen
To evaluate and compare the pharmacokinetic (PK) variable Cmax of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.
Measured: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen
Measured: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melflufen and desethyl-melflufen after central and peripheral intravenous infusion of melflufen
Measured: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen
To evaluate elimination half-life (t½) for melflufen, melphalan and desethyl-melflufen after central and peripheral intravenous infusion of melflufen.
Measured: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle)
Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT
To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.
Measured: Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)
To assess best response during the study with the criteria established by the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) for sCR, CR, VGPR, PR, SD and PD
Measured: From initiation of therapy until disease progression. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively.
ORR
To assess overall response rate (ORR), including CR/sCR, VGPR and PR, during the study with the criteria established by the IMWG-URC.
Measured: From initiation of therapy until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
CBR
To assess clinical benefit rate (CBR), i.e., proportion of patients that achieve a confirmed minimal response or better (sCR, CR, VGPR, PR and MR), during the study with the criteria established by the IMWG-URC.
Measured: To be assessed at the end of study drug treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
DOR
To assess duration of response (DOR): the time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, or PR to first confirmed disease progression according to the criteria established by the IMWG-URC or to death due to any cause. DOR is defined only for patients with a confirmed PR or better.
Measured: From confirmed response until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
DOCB
To assess duration of clinical benefit (DOCB) in patients with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), PR, or MR during the study with the criteria established by the IMWG-URC.
Measured: From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTR
To assess time to response (TTR) in patients with PR or better during the study with the criteria established by the UMWG-URC.
Measured: From initiation of therapy until documented disease response. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTP
To assess time to progression (TTP) during the study with the criteria established by the IMWG-URC.
Measured: From date of randomization until documented disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTNT
To assess time to next treatment (TTNT)
Measured: From randomization to the date of next anti-myeloma treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
PFS
To assess progression free survival (PFS)
Measured: From initiation of therapy until documented disease progression or initiation of new therapy. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)
To assess safety and general tolerability of melflufen by collecting non-serious Adverse Events (AEs) from the start of study treatment until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first. Serious AEs (SAEs) were collected from the time the subject signed the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever occurred first.
Measured: Median treatment durations for Arm A and Arm B were 29.14 and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
Grade 5 Treatment-Emergent Adverse Events (TEAEs)
To assess safety and general tolerability of melflufen by collecting serious adverse events (SAEs) from the signing of the ICF until 30 days after the last dose of any study drug (melflufen or dexamethasone) or initiation of subsequent therapy whichever comes first.
Measured: From signing of the ICF until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever comes first. Median treatment durations for Arms A and B were 29.14 weeks and 12.14 weeks. AE reporting period=30 days longer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start4 Aug 2020
- Primary completion2 Jun 2021
- Study completion10 Jan 2022
Why it stopped: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for RRMMStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oncopeptides AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04412707
- Sponsor's protocol ID
- OP-109
- Acronym
- PORT
- Status last verified
- Jan 2023
- First submitted
- 18 May 2020
- Last updated
- 9 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Two-period, Cross-over, Phase 2 Study, Comparing Pharmacokinetics, and Assessing Safety and Tolerability of Peripheral and Central i.v. Administration of Melphalan Flufenamide (Melflufen) in RRMM Patients
- ClinicalTrials.gov ID
- NCT04412707
- Acronym / sponsor ID
- PORT / OP-109
- Conditions
- RRMM
- Keywords
- central intravenous administration, peripheral intravenous administration, central venous catheter (CVC), peripheral venous catheter (PVC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Oncopeptides ABIndustry (pharma, biotech, devices)
- Study start
- 4 Aug 2020 (actual)
- Primary completion
- 2 Jun 2021 (actual)
- Study completion
- 10 Jan 2022 (actual)
- First posted
- 2 Jun 2020 (actual)
- Results
- Posted 16 Aug 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, two-period, cross-over Phase 2 study, comparing PK, and assessing safety and tolerability and efficacy of peripheral and central intravenous administration of melflufen in patients with RRMM. It is an international study, enrolling patients in US and Europe. The study will enroll patients following at least 2 lines of prior therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Active comparator | Drug: Melphalan, Drug: DexamethasoneMelflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Peripheral Venous Catheter (PVC) and cycle 2 and onwards melflufen will be administered via a Central Venous Catheter (CVC). |
| Arm B | Active comparator | Drug: Melphalan, Drug: DexamethasoneMelflufen 40 mg iv Day 1 of each 28 day cycle. Dexamethasone 40 mg po Day 1,8, 15 and 22 of each 28 day cycle, if > 75 years of age 20 mg. Cycle 1 will be administered via a Central Venous Catheter (CVC) and cycle 2 will be administered via a Peripheral Venous Catheter (PVC). From cycle 3 and onwards melflufen will be administered via CVC. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Male or female, age 18 years or older
- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol;
- A prior diagnosis of multiple myeloma (MM) with documented disease progression in need of treatment at time of screening;
- Measurable disease defined as any of the following:
- Received at least 2 prior lines of therapy and is refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI). The definition of refractory includes intolerance to an IMiD/PI after at least two 28-day cycles of therapy, see Appendix 10 and Appendix 8.
Key exclusion criteria (25 listed)
- Primary refractory disease (i.e. never responded with at least minimal response [MR] to any prior therapy);
- Evidence of mucosal and/or internal bleeding or platelet transfusion refractory (platelet count fails to increase by > 10,000 cells/mm³ after a 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 cardiac conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months);
- Known active infection that is uncontrolled or has required intravenous systemic therapy within 14 days of randomization. Patients that have required oral anti-infective treatment within 14 days of randomization should be discussed with the Medical Monitor;
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelphalanAlso: melflufen flufenamidePeripheral versus central administration | Drug | Arm A, Arm B |
| DexamethasoneOral tablets | Drug | Arm A, Arm B |
Primary outcome
Peak Plasma Concentration for Melphalan
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
To evaluate and compare the pharmacokinetic (PK) variable Cmax of melphalan after central and peripheral intravenous infusion of melflufen.
Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melphalan
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-t) of melphalan after central and peripheral intravenous infusion of melflufen.
Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melphalan
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
To evaluate and compare the pharmacokinetic (PK) variable AUC(0-inf) of melphalan after central and peripheral intravenous infusion of melflufen
Number of Participants With Local Reactions Including Phlebitis at Infusion Site After Peripheral Intravenous Administration
Time frame: 15 minutes and 4 hours after peripheral intravenous administration, pre- and post-infusion on Day 1 and Day 8
Assessment of the local tolerability of peripheral intravenous administration of melflufen using the Visual Infusion Phlebitis (VIP) scale. The VIP scale provides a score from 0 to 5, noting an ascending order of severity of inflammation. A score of 0 is the lowest possible score, meaning no inflammation detected, and 5 is the highest score, indicating the most severe reaction.
16 secondary outcomes
Peak Plasma Concentration for Melflufen and Desethyl-melflufen
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Area Under the Plasma Concentration Versus Time Curve AUC(0-t) of Melflufen and Desethyl-melflufen
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Area Under the Plasma Concentration Versus Time Curve AUC(0-inf) of Melflufen and Desethyl-melflufen
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 PK samples during and post infusion (28 days cycle)
Elimination Half-life (t1/2) of Melflufen, Melphalan and Desethyl-melflufen
Time frame: Cycle 1 Day 1 and Cycle 2 Day 1 - 13 measurements during and post infusion (28 days cycle)
Frequency of Treatment-Emergent Adverse Events (TEAEs) by MedDRA SOC and PT
Time frame: Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
Best Response (Stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD)
Time frame: From initiation of therapy until disease progression. Median treatment durations for Arm A and Arm B were 29.14 weeks and 12.14 weeks, respectively.
ORR
Time frame: From initiation of therapy until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
CBR
Time frame: To be assessed at the end of study drug treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
DOR
Time frame: From confirmed response until disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
DOCB
Time frame: From first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTR
Time frame: From initiation of therapy until documented disease response. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTP
Time frame: From date of randomization until documented disease progression. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
TTNT
Time frame: From randomization to the date of next anti-myeloma treatment. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
PFS
Time frame: From initiation of therapy until documented disease progression or initiation of new therapy. Maximum treatment durations for Arm A and Arm B were 68.4 and 59.0 weeks, respectively.
Grade 3/4 Treatment-Emergent Adverse Events (TEAEs)
Time frame: Median treatment durations for Arm A and Arm B were 29.14 and 12.14 weeks, respectively. The AE reporting period is estimated to be 30 days longer.
Grade 5 Treatment-Emergent Adverse Events (TEAEs)
Time frame: From signing of the ICF until 30 days after the last dose of any study drug or initiation of subsequent therapy, whichever comes first. Median treatment durations for Arms A and B were 29.14 weeks and 12.14 weeks. AE reporting period=30 days longer
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Relapsed or Refractory Multiple Myeloma (RRMM)
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
RecruitingPhase 3
A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1/2
A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1
A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melphalan and Dexamethasone in people with RRMM, run by Oncopeptides AB at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Ukraine, Bulgaria, Czechia, Hungary, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Plasma Concentration for Melphalan (time frame: Cycle 1 Day 1 and Cycle 2 Day 1. Samples were collected 5, 10, 15, 20, and 25 minutes after the start of the infusion; immediately before the end of the infusion; and 5, 10, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2023.