Relapsed and/or Relapsed-refractory Multiple MyelomaPhase 1/2NCT01897714

Safety and Efficacy of Melflufen and Dexamethasone in Relapsed and/or Relapsed-Refractory Multiple Myeloma Patients

A Phase 1/2 study testing Melflufen and Dexamethasone in people with Relapsed and/or Relapsed-refractory Multiple Myeloma, run by Oncopeptides AB at 7 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The study will explore escalating doses of melflufen in combination with dexamethasone in small groups of patients to find the maximum tolerated dose of melflufen. That dose will then be used to determine the efficacy and safety profile of melflufen in combination with dexamethasone in a larger group of patients. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Relapsed and/or Relapsed-refractory Multiple Myeloma
What is being tested?: Melflufen 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: 75 participants
Where: 7 sitesin 5 countries
Study dates: Jul 2013to Mar 2020
Phase: Phase 1/2
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
Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
Patient has measurable disease defined as any of the following:
Serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis
≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
Serum immunoglobulin free light chain ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio

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If no monoclonal protein is detected, then ≥ 30% monoclonal bone marrow plasma cells
Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
Life expectancy of ≥6 months
Patient has an ECOG performance status ≤ 2 (Patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible)
Females of childbearing potential must have a negative serum or urine pregnancy test prior to patient registration
Female patients of child bearing potential and non-vasectomized male patients 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
The patient has, or accepts to have, an acceptable infusion device for infusion of melflufen
12 lead ECG with QtcF interval ≤ 470 msec
The following laboratory results must be met within 21 days of patient registration:
Absolute neutrophil count ≥ 1,000 cells/dL (1.0 x 109/L)
Platelet count ≥ 75,000 cells/dL (75 x 109/L)
Hemoglobin ≥ 8.0 g/dL
Total Bilirubin ≤ 1.5 x upper limit of normal
Renal function: Estimated creatinine clearance ≥ 45 ml/min or serum creatinine ≤ 2.5 mg/dL
AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN

Who cannot join

Patient has 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 participation in this study
Known active infection requiring parenteral or oral anti-infective treatment
Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix
Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration.
Pregnant or breast-feeding females

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Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
Known HIV or hepatitis B or C viral infection
Patient has concurrent symptomatic amyloidosis or plasma cell leukemia
POEMS syndrome
Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to start of study treatment. Biologic, novel therapy (including investigational agents in this class) or corticosteroids within 2 weeks prior to patient registration. Patient has side effects of the previous therapy > grade 1 or previous baseline.
Prior peripheral stem cell transplant within 12 weeks of patient registration
Radiotherapy within 21 days prior to Cycle 1 Day 1. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy
Known intolerance to steroid therapy

Trial locations and contacts

7 sites in 5 countries.

Country

City, postcode or hospital

7 sites in 5 countries

United States3 sites

Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Universtity of North Carolina
Chapel Hill, North Carolina, 27514
Karmanos Cancer Center
Detroit, Michigan, 48201

Other trials in United States

Denmark1 site

Vejle Hospital
Vejle

Other trials in Denmark

Italy1 site

Turin Hospital Myeloma Unit
Turin

Other trials in Italy

Netherlands1 site

Erasmus University Medical Center
Rotterdam

Other trials in Netherlands

Sweden1 site

Sahlgrenska Hospital
Gothenburg

Other trials in Sweden

About this study

Official title: An Open-Label Phase I/IIa Study of the Safety and Efficacy of Melphalan-flufenamide (Melflufen) and Dexamethasone Combination for Patients With Relapsed and/or Relapsed-Refractory Multiple Myeloma

Conditions: Relapsed and/or Relapsed-refractory Multiple Myeloma
Being tested: Melflufen, Dexamethasone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MelflufenDrug
DexamethasoneDrug

Study groups in NCT01897714
Study group	Role	What they receive
Phase I: Melflufen 15 mg + Dexamethasone	Experimental	Intravenous (IV) infusion of 15 milligram (mg) melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle. Receives: Drug: Melflufen; Drug: Dexamethasone
Phase I: Melflufen 25 mg + Dexamethasone	Experimental	IV infusion of 25 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle. Receives: Drug: Melflufen; Drug: Dexamethasone
Phase I: Melflufen 40 mg + Dexamethasone	Experimental	IV infusion of 40 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle. Receives: Drug: Melflufen; Drug: Dexamethasone
Phase I: Melflufen 55 mg + Dexamethasone	Experimental	IV infusion of 55 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle. Receives: Drug: Melflufen; Drug: Dexamethasone
Phase I + II: Melflufen 40 mg + Dexamethasone	Experimental	IV infusion of 40 mg melflufen on Day 1 of each 21-day or 28-day treatment cycles, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycles. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each treatment cycle. Receives: Drug: Melflufen; Drug: Dexamethasone
Phase II: Melflufen 40 mg (Single Agent)	Experimental	IV infusion of 40 mg melflufen on Day 1 of each 28-day treatment cycle. Receives: Drug: Melflufen

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Patients Who Achieved Best Overall Disease Response
The best overall disease response on treatment including 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) were evaluated. Starting on completion of Cycle 2, response was assessed according to International Myeloma Working Group (IMWG) criteria based on Investigator's assessment for all patients at every cycle during treatment period. PD was defined as increase of ≥25% from lowest response value in any 1 of the following: serum M-component (absolute increase must be ≥0.5 gram/deciliter) and/or urine M-component (absolute increase must be ≥200 mg/24 hr); development of new bone lesions or soft tissue plasmacytomas or increase in size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that could be attributed solely to plasma cell proliferative disorder. SD was defined as not meeting criteria for CR, VGPR, PR or PD.
Measured: Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Overall Response Rate (ORR)
ORR was defined as percentage of patients with an overall response (OR), defined as first occurrence of confirmed disease response including PR or better (i.e, PR, VGPR, CR or sCR). Starting on completion of Cycle 2, response was assessed according to IMWG criteria based on Investigator's assessment for all patients at every cycle during treatment period. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum plus urine M-protein level <100 mg/24hr and >90% decrease in difference between involved and uninvolved free light chain (FLC) levels (only in FLC diseased patients). CR was defined as negative immunofixation on serum and urine, loss of any soft tissue plasmacytomas, <5% plasma cells in bone marrow and normal FLC ratio of 0.26 to 1.65 (only in FLC diseased patients). sCR was defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or 2 to 4 color flow cytometry.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Clinical Benefit Response Rate (CBRR)
The CBRR was defined as the percentage of patients with a clinical benefit response (CBR), defined as the first occurrence of confirmed disease response including MR or better (i.e, MR, PR, VGPR, CR, or sCR). Starting on completion of Cycle 2, response was assessed according to the IMWG criteria based on the Investigator's assessment for all patients at every cycle during the treatment period. MR was defined as ≥25% but <49% reduction of serum M-protein and reduction in 24 hour urine M-protein by 50 to 89%, which still exceeds 200 mg/24 hours. In addition to above; if present at baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fractures does not exclude response). PR was defined as 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥90% or to <200 mg/24 hour.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.

Secondary outcomes (7)

Duration of Disease Response (DOR)
The DOR to treatment was defined as time from first response (PR or better) to disease progression or death, or date of last evaluable disease response assessment for those who had not progressed or died. DOR was estimated using Kaplan-Meier statistics.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Response in Patients Who Achieved OR and CBR
Time to first OR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of PR or better (first of 2 consecutive assessments-confirmed response). Time to first CBR was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of MR or better (first of 2 consecutive assessments-confirmed response). Time to disease response was estimated using Kaplan-Meier statistics.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Progression
Time to disease progression was defined as the time from the date of the first dose of study drug (overall reference start date) to the date of the first occurrence of evaluable PD. Time to disease progression was estimated using Kaplan-Meier statistics.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Progression-Free Survival (PFS)
The PFS was defined as the time from the date of the first dose of melflufen (overall reference start date) to the date of the first occurrence of any disease response assessment available for PD or death. The PFS was estimated using Kaplan-Meier statistics.
Measured: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Overall Survival (OS)
The OS was defined as the time from the date of the first dose of melflufen (overall reference start date) to death. The OS was estimated using Kaplan-Meier statistics.
Measured: From baseline until death. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to First Subsequent Treatment
Time to first subsequent treatment start was defined as the time from the date of the actual end of treatment to the date of the first subsequent treatment. Time to first subsequent treatment was estimated using Kaplan-Meier statistics.
Measured: From baseline until start of first subsequent treatment. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a study patient administered an investigational product and that does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was defined as any AE, occurring at any dose, that met any one or more of the following criteria: is fatal or immediately life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; is medically significant; requires inpatient hospitalization or prolongation of existing hospitalization; or other important medical event. TEAEs were defined as AEs that started or worsened on or after the first dose of study drug (overall reference start date) up to and including the actual EOT date. TESAEs = Treatment emergent serious adverse events.
Measured: From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2013Mar 2020

First posted12 Jul 2013 (estimated)
Study startJul 2013
Primary completionDec 2017
Study completionMar 2020

Why it stopped: The study was terminated at median 46-48 months long term follow-up and mature overall survival follow-up data.

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Relapsed and/or Relapsed-refractory Multiple MyelomaStudies 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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 75 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01897714
Sponsor's protocol ID: O-12-M1
Status last verified: Oct 2020
First submitted: 9 Jul 2013
Last updated: 23 Oct 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Richardson PG, Bringhen S, Voorhees P, Plesner T, Mellqvist UH, Reeves B, Paba-Prada C, Zubair H, Byrne C, Chauhan D, Anderson K, Nordstrom E, Harmenberg J, Palumbo A, Sonneveld P. Melflufen plus dexamethasone in relapsed and refractory multiple myeloma (O-12-M1): a multicentre, international, open-label, phase 1-2 study. Lancet Haematol. 2020 May;7(5):e395-e407. doi: 10.1016/S2352-3026(20)30044-2. Epub 2020 Mar 23.
PubMed 32213344

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Multiple Myeloma
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Testing the Investigational Medication Combination of Daratumumab and Teclistamab Compared to the Usual Treatment (Daratumumab, Pomalidomide, Dexamethasone or Daratumumab, Carfilzomib, Dexamethasone) for Patients With High-risk Multiple Myeloma Refractory or in First Relapse
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All Relapsed and/or Relapsed-refractory Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 23 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-Label Phase I/IIa Study of the Safety and Efficacy of Melphalan-flufenamide (Melflufen) and Dexamethasone Combination for Patients With Relapsed and/or Relapsed-Refractory Multiple Myeloma
ClinicalTrials.gov ID: NCT01897714
Acronym / sponsor ID: O-12-M1
Conditions: Relapsed and/or Relapsed-refractory Multiple Myeloma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated at median 46-48 months long term follow-up and mature overall survival follow-up data.
Enrolment: 75 participants (actual)
Lead sponsor: Oncopeptides ABIndustry (pharma, biotech, devices)
Study start: Jul 2013 (actual)
Primary completion: Dec 2017 (actual)
Study completion: Mar 2020 (actual)
First posted: 12 Jul 2013 (estimated)
Results: Posted 24 Aug 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
Phase I: Melflufen 15 mg + Dexamethasone	Experimental	Drug: Melflufen, Drug: DexamethasoneIntravenous (IV) infusion of 15 milligram (mg) melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Phase I: Melflufen 25 mg + Dexamethasone	Experimental	Drug: Melflufen, Drug: DexamethasoneIV infusion of 25 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Phase I: Melflufen 40 mg + Dexamethasone	Experimental	Drug: Melflufen, Drug: DexamethasoneIV infusion of 40 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Phase I: Melflufen 55 mg + Dexamethasone	Experimental	Drug: Melflufen, Drug: DexamethasoneIV infusion of 55 mg melflufen on Day 1 of each 21-day treatment cycle, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycle.
Phase I + II: Melflufen 40 mg + Dexamethasone	Experimental	Drug: Melflufen, Drug: DexamethasoneIV infusion of 40 mg melflufen on Day 1 of each 21-day or 28-day treatment cycles, in combination with 40 mg dexamethasone (oral or IV) on Days 1, 8 and 15 of each 21-day treatment cycles. For any patients on the 28-day treatment schedule, an additional dose of 40 mg dexamethasone was administered on Day 22 of each treatment cycle.
Phase II: Melflufen 40 mg (Single Agent)	Experimental	Drug: MelflufenIV infusion of 40 mg melflufen on Day 1 of each 28-day treatment cycle.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (22 listed)

Male or female, age 18 years or older
Patient has a diagnosis of multiple myeloma with documented relapsed and/or relapsed-refractory disease
Patient has measurable disease defined as any of the following:
Patient has had at least 2 or more prior lines of therapy including lenalidomide and bortezomib and has demonstrated disease progression on or within 60 days of completion of the last therapy
Life expectancy of ≥6 months

Key exclusion criteria (14 listed)

Patient has 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 participation in this study
Known active infection requiring parenteral or oral anti-infective treatment
Other malignancy within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix
Other ongoing anti-myeloma therapy. Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids for symptom management and comorbid conditions. Doses of corticosteroid should be stable for at least 7 days prior to patient registration.

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
Melflufen	Drug	Phase I + II: Melflufen 40 mg + Dexamethasone, Phase I: Melflufen 15 mg + Dexamethasone, Phase I: Melflufen 25 mg + Dexamethasone, Phase I: Melflufen 40 mg + Dexamethasone, Phase I: Melflufen 55 mg + Dexamethasone, Phase II: Melflufen 40 mg (Single Agent)
Dexamethasone	Drug	Phase I + II: Melflufen 40 mg + Dexamethasone, Phase I: Melflufen 15 mg + Dexamethasone, Phase I: Melflufen 25 mg + Dexamethasone, Phase I: Melflufen 40 mg + Dexamethasone, Phase I: Melflufen 55 mg + Dexamethasone

Primary outcome

Percentage of Patients Who Achieved Best Overall Disease Response
Time frame: Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
The best overall disease response on treatment including 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) were evaluated. Starting on completion of Cycle 2, response was assessed according to International Myeloma Working Group (IMWG) criteria based on Investigator's assessment for all patients at every cycle during treatment period. PD was defined as increase of ≥25% from lowest response value in any 1 of the following: serum M-component (absolute increase must be ≥0.5 gram/deciliter) and/or urine M-component (absolute increase must be ≥200 mg/24 hr); development of new bone lesions or soft tissue plasmacytomas or increase in size of existing bone lesions or soft tissue plasmacytomas or development of hypercalcemia that could be attributed solely to plasma cell proliferative disorder. SD was defined as not meeting criteria for CR, VGPR, PR or PD.
Overall Response Rate (ORR)
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
ORR was defined as percentage of patients with an overall response (OR), defined as first occurrence of confirmed disease response including PR or better (i.e, PR, VGPR, CR or sCR). Starting on completion of Cycle 2, response was assessed according to IMWG criteria based on Investigator's assessment for all patients at every cycle during treatment period. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum plus urine M-protein level <100 mg/24hr and >90% decrease in difference between involved and uninvolved free light chain (FLC) levels (only in FLC diseased patients). CR was defined as negative immunofixation on serum and urine, loss of any soft tissue plasmacytomas, <5% plasma cells in bone marrow and normal FLC ratio of 0.26 to 1.65 (only in FLC diseased patients). sCR was defined as CR plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or 2 to 4 color flow cytometry.
Clinical Benefit Response Rate (CBRR)
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
The CBRR was defined as the percentage of patients with a clinical benefit response (CBR), defined as the first occurrence of confirmed disease response including MR or better (i.e, MR, PR, VGPR, CR, or sCR). Starting on completion of Cycle 2, response was assessed according to the IMWG criteria based on the Investigator's assessment for all patients at every cycle during the treatment period. MR was defined as ≥25% but <49% reduction of serum M-protein and reduction in 24 hour urine M-protein by 50 to 89%, which still exceeds 200 mg/24 hours. In addition to above; if present at baseline, 25 to 49% reduction in the size of soft tissue plasmacytomas is also required. No increase in size or number of lytic bone lesions (development of compression fractures does not exclude response). PR was defined as 50% reduction of serum M-protein and reduction in 24 hour urinary M-protein by ≥90% or to <200 mg/24 hour.

7 secondary outcomes

Duration of Disease Response (DOR)
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Response in Patients Who Achieved OR and CBR
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to Disease Progression
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Progression-Free Survival (PFS)
Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Median Overall Survival (OS)
Time frame: From baseline until death. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Time to First Subsequent Treatment
Time frame: From baseline until start of first subsequent treatment. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.
Number of Patients With Treatment Emergent Adverse Events (TEAEs)
Time frame: From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.

Results and safety

Results posted to the registry on 24 Aug 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I: Melflufen 15 mg + Dexamethasone	4	1
Phase I: Melflufen 25 mg + Dexamethasone	7	0
Phase I: Melflufen 40 mg + Dexamethasone	6	1
Phase I: Melflufen 55 mg + Dexamethasone	6	0
Phase I + II: Melflufen 40 mg + Dexamethasone	0	0
Phase II: Melflufen 40 mg (Single Agent)	0	0

Primary outcome: Percentage of Patients Who Achieved Best Overall Disease Response

Time frame: Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.. Number (95% Confidence Interval). Unit: percentage of patients

Measure	Phase I: Melflufen 15 mg + Dexamethasone n = 4	Phase I: Melflufen 25 mg + Dexamethasone n = 7	Phase I: Melflufen 40 mg + Dexamethasone n = 6	Phase I: Melflufen 55 mg + Dexamethasone n = 6	Phase I + II: Melflufen 40 mg + Dexamethasone n = 45	Phase II: Melflufen 40 mg (Single Agent) n = 13
sCR	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	0.0 (0.0 to 45.9)	0.0 (0.0 to 7.9)	0.0 (0.0 to 24.7)
CR	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	0.0 (0.0 to 45.9)	0.0 (0.0 to 7.9)	0.0 (0.0 to 24.7)
VGPR	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	16.7 (0.4 to 64.1)	16.7 (0.4 to 64.1)	11.1 (3.7 to 24.1)	0.0 (0.0 to 24.7)
PR	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	50.0 (11.8 to 88.2)	0.0 (0.0 to 45.9)	20.0 (9.6 to 34.6)	7.7 (0.2 to 36.0)
MR	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	0.0 (0.0 to 45.9)	17.8 (8.0 to 32.1)	15.4 (1.9 to 45.4)
SD	75.0 (19.4 to 99.4)	42.9 (9.9 to 81.6)	16.7 (0.4 to 64.1)	66.7 (22.3 to 95.7)	26.7 (14.6 to 41.9)	69.2 (38.6 to 90.9)
PD	25.0 (0.6 to 80.6)	57.1 (18.4 to 90.1)	16.7 (0.4 to 64.1)	16.7 (0.4 to 64.1)	15.6 (6.5 to 29.5)	7.7 (0.2 to 36.0)
Missing	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	0.0 (0.0 to 45.9)	0.0 (0.0 to 45.9)	8.9 (2.5 to 21.2)	0.0 (0.0 to 24.7)

Population analysed: For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug. For Phase II arms: Modified Intent-to-Treat (mITT) Analysis Set included all patients considered to be valid for Safety Analysis Set and who received at least 1 dose of study drug at the MTD as initial dose.

Primary outcome: Overall Response Rate (ORR)

Time frame: Baseline and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.. Number (95% Confidence Interval). Unit: percentage of patients

Measure	Phase I: Melflufen 15 mg + Dexamethasone n = 4	Phase I: Melflufen 25 mg + Dexamethasone n = 7	Phase I: Melflufen 40 mg + Dexamethasone n = 6	Phase I: Melflufen 55 mg + Dexamethasone n = 6	Phase I + II: Melflufen 40 mg + Dexamethasone n = 45	Phase II: Melflufen 40 mg (Single Agent) n = 13
Value	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	66.7 (22.3 to 95.7)	16.7 (0.4 to 64.1)	31.1 (18.2 to 46.6)	7.7 (0.2 to 36.0)

Population analysed: For Phase I arms: The Safety Analysis Set included all patients who received at least 1 dose, or part thereof, of study drug. For Phase II arms: The mITT Analysis Set included all patients considered to be valid for the Safety Analysis Set and who received at least 1 dose of study drug at the MTD as the initial dose.

Primary outcome: Clinical Benefit Response Rate (CBRR)

Measure	Phase I: Melflufen 15 mg + Dexamethasone n = 4	Phase I: Melflufen 25 mg + Dexamethasone n = 7	Phase I: Melflufen 40 mg + Dexamethasone n = 6	Phase I: Melflufen 55 mg + Dexamethasone n = 6	Phase I + II: Melflufen 40 mg + Dexamethasone n = 45	Phase II: Melflufen 40 mg (Single Agent) n = 13
Value	0.0 (0.0 to 60.2)	0.0 (0.0 to 41.0)	66.7 (22.3 to 95.7)	16.7 (0.4 to 64.1)	48.9 (33.7 to 64.2)	23.1 (5.0 to 53.8)

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of study drug up to and including the actual EOT date of 29 October 2019; up to a maximum of approximately 76 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I: Melflufen 15 mg + Dexamethasone	3 of 4 (75%)	4 of 4 (100%)	3 of 4
Phase I: Melflufen 25 mg + Dexamethasone	4 of 7 (57.1%)	7 of 7 (100%)	5 of 7
Phase I: Melflufen 40 mg + Dexamethasone	2 of 6 (33.3%)	6 of 6 (100%)	2 of 6
Phase I: Melflufen 55 mg + Dexamethasone	4 of 6 (66.7%)	6 of 6 (100%)	5 of 6
Phase I + II: Melflufen 40 mg + Dexamethasone	17 of 45 (37.8%)	45 of 45 (100%)	30 of 45
Phase II: Melflufen 40 mg (Single Agent)	9 of 13 (69.2%)	12 of 13 (92.3%)	10 of 13

Limitations and caveats (from the sponsor): Study is terminated and long-term follow-up ended due to Sponsor decision.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 32213344Richardson PG, Bringhen S, Voorhees P, Plesner T, Mellqvist UH, Reeves B, Paba-Prada C, Zubair H, Byrne C, Chauhan D, Anderson K, Nordstrom E, Harmenberg J, Palumbo A, Sonneveld P. Melflufen plus dexamethasone in relapsed and refractory multiple myeloma (O-12-M1): a multicentre, international, open-label, phase 1-2 study. Lancet Haematol. 2020 May;7(5):e395-e407. doi: 10.1016/S2352-3026(20)30044-2. Epub 2020 Mar 23.

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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.

Paul G Richardson, MD study director

Dana Farber Cancer Institute, Boston MA, USA

Johan Harmenberg, MD study director

Oncopeptides AB, Stockholm, Sweden

7 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Melflufen and Dexamethasone in people with Relapsed and/or Relapsed-refractory Multiple Myeloma, run by Oncopeptides AB at 7 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 22 inclusion and 14 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 23 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in United States, Denmark, Italy, Netherlands, Sweden. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 24 Aug 2020). 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?

Percentage of Patients Who Achieved Best Overall Disease Response (time frame: Baseline (Cycle 1 Day 1) and every cycle from Cycle 2 onwards until confirmed disease progression. Assessed until EOT date of 29 October 2019; up to a maximum of approximately 76 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01897714, which also lists 1 linked publication.

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 23 Oct 2020.