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Multiple MyelomaPhase 1/2ANCHORNCT03481556

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

A Phase 1/2 study testing Melphalan flufenamide (Melflufen), Dexamethasone and Bortezomib in people with Multiple Myeloma, run by Oncopeptides AB at 16 sites in 4 countries.

Terminated

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

Official record
Search all trials

Trial summary

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

Who is it for?
Ages 18 years and older
Conditions the study is for
Multiple Myeloma
What is being tested?
Melphalan flufenamide (Melflufen), Dexamethasone and Bortezomib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
16 sitesin 4 countries
Study dates
12 Apr 2018to 2 Feb 2022
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
  • A prior diagnosis of multiple myeloma with documented disease progression in need of treatment at time of screening
  • One to four prior lines of therapy
  • Measurable disease defined as any of the following:
  • Serum monoclonal protein ≥ 0.5 g/dL by serum protein electrophoresis (SPEP)
  • ≥ 200 mg/24 hours of monoclonal protein in the urine on 24-hour urine electrophoresis (UPEP)
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  • Serum free light chain (SFLC) ≥ 10 mg/dL AND abnormal serum kappa to lambda free light chain ratio
  • Life expectancy of ≥ 6 months
  • ECOG performance status ≤ 2. (Patients with lower performance status based solely on bone pain secondary to multiple myeloma may be eligible following consultation and approval of the medical monitor)
  • Patient is a female of childbearing potential (FCBP)* with a negative serum or urine pregnancy test prior to initiation of therapy and agrees to practice appropriate methods of birth control, or the patient is male and agrees to practice appropriate methods of birth control
  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent
  • 12-lead Electrocardiogram (ECG) with QT interval calculated by Fridericia Formula (QTcF) interval of ≤ 470 msec
  • Adequate organ function with the following laboratory results during screening (within 21 days) and immediately before study drug administration on Cycle 1 Day 1:
  • Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3 (1.0 x 109/L) (Growth factors cannot be used within 10 days (14 days for pegfilgrastim) prior to initiation of therapy)
  • Platelet count ≥ 75,000 cells/mm3 (75 x 109/L) (without required transfusions during the 10 days prior to initiation of therapy)
  • Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted)
  • Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), or patients diagnosed with Gilbert's syndrome, that have been reviewed and approved by the medical monitor
  • AST/SGOT and ALT/SGPT ≤ 3.0 x ULN
  • Renal function: Estimated creatinine clearance by Cockcroft-Gault formula ≥ 45 mL/min and serum creatinine ≤ 2 mg/dL
  • Must have, or be willing to have an acceptable central catheter. (Port a cath, peripherally inserted central catheter [PICC] line, or central venous catheter)
  • Regimen A
  • Must be intolerant or refractory to a prior IMiD; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose.
  • Regimen B
  • Must have had a prior IMiD and a proteasome inhibitor (PI); alone or in combination and must be refractory or intolerant to an IMiD, PI or both.
  • (FCBP) is any sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (not having menstrual cycles due to cancer therapy does not rule out childbearing potential) for at least 24 consecutive months.

Who cannot join

  • Primary refractory disease (i.e. never responded with ≥ MR to any prior therapy)
  • Evidence of mucosal or internal bleeding and/or are platelet transfusion refractory (i.e. platelet count fails to increase by > 10,000 cells/mm3 after transfusion of an appropriate dose of platelets)
  • Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study. Examples of such conditions are: a significant history of cardiovascular disease (e.g., myocardial infarction, significant conduction system abnormalities, uncontrolled hypertension, ≥ Grade 3 thromboembolic event in the last 6 months)
  • Known active infection requiring parenteral or oral anti-infective treatment within 14 days of initiation of therapy
  • Other malignancy diagnosed or requiring treatment within the past 3 years with the exception of adequately treated basal cell carcinoma, squamous cell skin cancer, carcinoma in-situ of the cervix or breast or very low and low risk prostate cancer in active surveillance
  • Pregnant or breast-feeding females
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  • Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse compliance or follow-up evaluation
  • Known human immunodeficiency virus or active hepatitis B or C viral infection
  • Concurrent symptomatic amyloidosis or plasma cell leukemia
  • POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
  • Previous cytotoxic therapies, including cytotoxic investigational agents, for multiple myeloma within 3 weeks (6 weeks for nitrosoureas) prior to initiation of therapy. The use of live vaccines within 30 days before initiation of therapy. IMiDs, PIs and or corticosteroids within 2 weeks prior to initiation of therapy. Other investigational therapies and monoclonal antibodies (mAb) within 4 weeks of initiation of therapy Prednisone up to but no more than 10 mg orally once daily (q.d.) or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days prior to initiation of therapy
  • Residual side effects to previous therapy > Grade 1 prior to initiation of therapy (Alopecia any grade and/or neuropathy Grade 1 without pain are permitted)
  • Prior peripheral stem cell transplant within 12 weeks of initiation of therapy
  • Prior allogeneic stem cell transplantation with active graft-versus-host- disease
  • Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy)
  • Known intolerance to the required dose and schedule of steroid therapy as determined by the investigator
  • Prior treatment with melflufen
  • Regimen A
  • Refractory to a PI in the last line of therapy prior to enrollment in this trial; refractory defined as failure to respond (MR or better) or progression while on therapy or within 60 days of last dose
  • History of allergic reaction/hypersensitivity attributed to compounds containing boron, mannitol, polysorbate 80 or sodium citrate dihydrate
  • Regimen B
  • Prior exposure to an antiCD-38 mAb
  • Chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) less than 50% of predicted normal
  • Moderate or severe persistent asthma within the past 2 years, or currently has uncontrolled asthma of any classification
  • ≥ Grade 3 conduction system abnormalities unless patient has a pacemaker
  • Active hepatitis B (defined as HBsAg+) or those at risk for reactivation (HBsAg-, Anti- HBs+, Anti-HBc+)
  • Patients with prior hepatitis B vaccine are permitted (defined as HBsAg-, Anti-HBs+, Anti-HBc-)
  • Non-active hepatitis B (HBsAg-, Anti-HBs+, Anti-HBc+) may only be enrolled after approval of the sponsor and consideration of risk of reactivation (additional screening and monitoring for reactivation of Hepatitis B and consultation with a liver disease specialist may be required)

Trial locations and contacts

16 sites in 4 countries.

16 sites in 4 countries

France5 sites

  • Hôpital Morvan

    Brest

  • Centre Jean Bernard - Clinique Victor Hugo

    Le Mans

  • Hôpital privé du Confluent

    Nantes

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite

  • Centre Hospitalier Universitaire Institut Gustave Roussy

    Villejuif

Other trials in France

Spain5 sites

  • Hospital Universitai Germans Trias i Pujol

    Badalona

  • Hospital de la Santa Creu i Sant Pau

    Barcelona

  • Hospital Universitario 12 de Octubre

    Madrid

  • Complejo Hospitalario de Salamanca

    Salamanca

  • Hospital Universitario Marques de Valdecilla

    Santander

Other trials in Spain

Czechia4 sites

  • Fakultní nemocnice Brno

    Brno

  • Fakultní nemocnice Hradec Králové

    Hradec Králové

  • Fakultní nemocnice Ostrava

    Ostrava

  • Všeobecná fakultní nemocnice

    Prague

Other trials in Czechia

United States2 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • The Ohio State University

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: An Open-Label Phase 1/2a Study of the Safety and Efficacy of Melflufen and Dexamethasone in Combination With Either Bortezomib or Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma

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

Being tested
Melphalan flufenamide (Melflufen), Dexamethasone, Bortezomib, Daratumumab
Medical subject headings
Multiple Myeloma

What participants receive

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

  • Melphalan flufenamide (Melflufen)Drug

    Intravenous infusion

  • DexamethasoneDrug

    Also called Dex, Fortecortin, Decadron

    Oral tablets

  • BortezomibDrug

    Also called Velcade

    Subcutaneous administration

  • DaratumumabDrug

    Also called Dara, Darzalex

    Intravenous infusion

Study groups in NCT03481556
Study groupRoleWhat they receive
A (melflufen+bortezomib+dex)ExperimentalMelflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with bortezomib at 1.3mg/m² S.Q. on Days 1, 4, 8, 11 and dexamethasone 20 mg (12 mg ≥ 75 years) Days 1, 4, 8, 11 and 40 mg (20 mg ≥ 75 years) on Day 15 and 22 of each 28-day cycle.
Receives: Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone; Drug: Bortezomib
B (melflufen+daratumumab+dex)ExperimentalMelflufen 30 mg and 40 mg or 20 mg i.v. Day 1 of each 28-day cycle in combination with daratumumab 16 mg/kg weekly for 8 doses, every other week for 8 doses and then once every 4 weeks. Dexamethasone p.o. 40 mg weekly (20 mg weekly for patients age ≥ 75 years).
Receives: Drug: Melphalan flufenamide (Melflufen); Drug: Dexamethasone; Drug: Daratumumab

What is being measured

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

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

    Toxicity was graded according to the National Cancer Institute - Common Terminology Criteria for Adverse Events Version 4.03.

    DLT criteria that apply to Regimens A and B:

    • Grade 3 non-hematologic toxicity preventing the administration of > 1 dose of bortezomib or daratumumab during the 1st cycle.
    • Grade 4 or greater non-hematologic toxicity.
    • Grade 4 thrombocytopenia (platelet count < 25,000 cells/ mm^3) preventing the administration of > 1 dose of bortezomib or daratumumab during the 1st cycle or with clinically significant bleeding during the 1st cycle.
    • Grade 4 neutropenia (ANC < 500 cells/mm^3), lasting more than 7 days during the 1st cycle.
    • Greater than 14 days' delay to meet the criteria for the start of a new cycle (Cycle 2) due to toxicity.

    Measured: Cycle 1: Day 1 to Day 28

  2. Phase 2: Overall Response Rate (ORR)

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

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

Secondary outcomes (10)

  1. Best Response (BR)

    BR defined by International Myeloma Working Group Uniform Response Criteria. BR= Complete Response (CR)/Stringent CR (sCR) defined as below negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow/plus normal free light chain (FLC) ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence, Very Good Partial Response (VGPR)= serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 hours, Partial Response (PR)= a > 50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by > 90% or to < 200 mg/24 hours, Minimal Response (MR), Stable Disease (SD)= not meeting the criteria for other response options, Progressive Disease (PD)= increase of > 25% from lowest response value in serum/urine M-component or bone marrow plasma cell percentage, or non-evaluable.

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

  2. Duration of Response (DOR)

    DOR is defined for participants with confirmed objective response (PR or better, which includes PR, VGPR, CR and sCR) as the time from the first documentation of objective response to the first documentation of objective progression or to death due to any cause, whichever occurs first.

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

  3. Time to Response (TTR)

    Time from Cycle 1 Day 1 to a response of PR or better.

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

  4. Progression-Free Survival (PFS)

    PFS was defined as the time in months from date of initiation of therapy to the earlier of confirmed disease progression or death due to any cause.

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

  5. Overall Survival (OS)

    Time from the first dose of melflufen to death due to any cause.

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

  6. Duration of Clinical Benefit (DOCB)

    DOCB was defined as time in months from the first evidence of confirmed assessment of sCR, CR, VGPR, PR or MR to first confirmed disease progression, or to death due to any cause.

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

  7. Time to Progression (TTP)

    TTP defined as time from first dose to first documented confirmed progression.

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

  8. Clinical Benefit Rate (≥ Minimal Response)

    ≥ Minimal response for participants included sCR, CR, VGPR, PR and MR.

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

  9. Time to Next Treatment (TTNT)

    Defined as time from date of initiation of therapy to start of next line of therapy.

    Measured: Until death or initiation of subsequent therapy (a maximum of 194.3 weeks)

  10. Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

    TEAEs were defined as adverse events (AEs) that started after the first dose of study medication was administered and within 30 days of the last administration of the study treatment or before start of subsequent anticancer treatment (whichever occurred first) or that worsened after the first dose of study medication was administered.

    Measured: Cycle 1 Day 1 up to a maximum of 198.9 weeks

Timeline

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

  1. First posted29 Mar 2018
  2. Study start12 Apr 2018
  3. Primary completion2 Feb 2022
  4. Study completion2 Feb 2022

Why it stopped: The sponsor decided to terminate the study following an FDA request of a partial clinical hold.

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03481556
Sponsor's protocol ID
OP-104
Acronym
ANCHOR
Status last verified
Dec 2022
First submitted
6 Mar 2018
Last updated
19 Dec 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Melphalan flufenamide (Melflufen), Dexamethasone and Bortezomib in people with Multiple Myeloma, run by Oncopeptides AB at 16 sites in 4 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 25 inclusion and 28 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 19 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in France, Spain, Czechia, 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 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 19 Dec 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?

Phase 1: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) (time frame: Cycle 1: Day 1 to Day 28). The study lists 2 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 NCT03481556.

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 19 Dec 2022; AzTrials last refreshed its copy on 26 Oct 2026.

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