Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Dexamethasone

Melphalan

Daratumumab

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Immunologic Factors

Treatment was given in 28-day cycles in an outpatient treatment setting.

* Melflufen 30 mg intravenous (i.v.) infusion on Day 1 of each cycle
* Dexamethasone 40 mg per oral (p.o.) weekly (20 mg p.o. weekly if ≥75 years)
* Daratumumab 1800 mg subcutaneously (s.c.) on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7

Treatment was given in 28-day cycles in an outpatient treatment setting.

• Daratumumab 1800 mg s.c. on Days 1, 8, 15, and 22 in Cycles 1 and 2, on Days 1 and 15 in Cycles 3 to 6, and on Day 1 from Cycle 7

Melflufen

Maria-Victorìa Mateos, MD, PhD

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with Relapsed-Refractory Multiple Myeloma (RRMM) who were either double refractory to an Immunomodulatory Drug (IMiD) and a Proteasome Inhibitor (PI) (regardless of the number of prior lines of therapy), or had received at least 3 prior lines of therapy including an IMiD and a PI.

Patients received treatment with melflufen+dexamethasone+daratumumab or daratumumab until documented progressive disease, unacceptable toxicity, or patient/treating physician decision. Patients in the daratumumab treatment arm had the option to receive treatment with melflufen+dexamethasone+daratumumab after confirmed progressive disease.

Independent Review Committee was planned to be blinded to treatment assignment. Due to the early termination, the response assessments were only done by investigators, not by an independent review committee.

Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma

A Randomized, Controlled, Open-Label Phase 3 Study of Melflufen in Combination With Daratumumab Compared With Daratumumab in Patients With Relapsed or Relapsed-Refractory Multiple Myeloma

Time from the date of randomization to the date of first documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first.

Proportion of patients who achieve a best-confirmed response of stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR).

Time from the first evidence of confirmed assessment of sCR, CR, VGPR or PR to first confirmed disease progression, or death due to any cause. DOR is defined only for patients with a confirmed PR or better.

Proportion of patients with sCR, CR, VGPR, PR, Minimal Response (MR), Stable Disease (SD), PD, or non-evaluable (NE).

The proportion of patients who achieve a best confirmed response of sCR, CR, VGPR, PR, or MR.

Time 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. DOCB is defined only for patients with a confirmed MR or better.

Time from randomization to the date of the first documented confirmed response in a patient who has responded with ≥PR.

Time from randomization to the date of the first documented confirmed PD

Time from randomization to the date of next anti-myeloma treatment or until death.

Time from randomization to death due to any cause.

Oncopeptides AB

AE definition: An AE is any untoward medical occurrence in a patient or clinical study patient, temporally associated with the use of study treatment, whether or not considered related to the study treatment.

AEs are grouped by MedDRA system organ class (SOC) and preferred term (PT).

Arm A (Melflufen+Dexamethasone+Daratumumab)

Arm B (Daratumumab)

Patients in Arm B were allowed to crossover and receive the same treatment as Arm A after a confirmed disease progression (2 patients crossed over).

Crossover (From Arm B to the Same Treatment as Arm A)

Total

Age, Continuous

65 - ≤75

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Weight

Height

0=Normal activity, fully active, able to carry on all pre-disease performance without restriction. 1=Symptoms, but fully ambulatory, restricted in physically strenuous but ambulatory and able to carry out work of a light or sedentary nature (e.g., light housework, office work). 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.

Eastern Cooperative Oncology Group (ECOG) score

This study was put on clinical hold and later discontinued prematurely. Due to this, there is limited data available, and data cleaning was not done according to the original plan. Due to the early termination, the response assessments were done by investigators, not by an independent review committee.

VP Chief Operating Officer

Analysis was performed using the Full Analysis Set (FAS).

Progression Free Survival (PFS)

Overall Response Rate (ORR)

Duration of Response (DOR)

Best Response

Clinical Benefit Rate (CBR)

Duration of Clinical Benefit (DOCB)

Time to Response (TTR)

Time to Progression (TTP)

Time to Next Treatment (TTNT)

Overall Survival (OS)

Arm A/Arm B Treatment

Crossover (Arm B)

Lenalidomide

Pomalidomide

BB 1101

Angiogenesis Inhibitors

Growth Inhibitors

Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Pomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Pieter Sonneveld, Prof.

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide. Patients received either melflufen+dex or pomalidomide+dex.

This was a randomized, controlled, open-label, Phase 3 multicenter study which enrolled patients with RRMM following 2-4 lines of prior therapy and who were refractory to lenalidomide in the last line of therapy as demonstrated by disease progression on or within 60 days of completion of the last dose of lenalidomide.

Patients were randomized to either one of two arms:

Arm A: Melphalan flufenamide (Melflufen) 40 mg on Day 1 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Arm B: Pomalidomide 4 mg daily on Days 1 to 21 and dexamethasone 40 mg on Days 1, 8, 15 and 22 of each 28-day cycle.

Patients ≥ 75 years of age received a reduced dose of dexamethasone of 20 mg on Days 1, 8, 15 and 22 for both Arm A and Arm B.

Patients were to receive treatment until such time as there was documented disease progression, unacceptable toxicity, or the patient/treating physician determined it was not in the patient's best interest to continue.

Dose modifications and delays in therapy may have been implemented based on patient tolerability as detailed in the protocol. In the event of a cycle delay, unrelated to dexamethasone toxicity, it was recommended to continue dexamethasone weekly.

A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide

A Randomized, Controlled, Open-label, Phase 3 Study of Melflufen/Dexamethasone Compared With Pomalidomide/Dexamethasone for Patients With Relapsed Refractory Multiple Myeloma Who Are Refractory to Lenalidomide

Progression Free Survival defined as the duration in months from randomization until first evidence of confirmed disease progression, as assessed by the Independent Review Committee (IRC) according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). Disease progression was defined according to the IMWG-URC as progressive disease or death due to any cause, whichever occurs first.

ORR defined as the proportion of patients for whom the best overall confirmed response is stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR), as assessed by IRC.

DOR defined as the duration in months from first documentation of a confirmed response to first evidence of confirmed disease progression or death due to any cause.

OS defined as the time in months from randomization to date of death due to any cause. Patients who were still alive at end of study, or lost to follow up, were censored at the last day the patient was known to be alive.

Number of patients with TEAEs, including clinical laboratory and vital signs abnormalities, as assessed by CTCAE v4.0 are presented. No formal statistical analysis was performed for safety endpoints.

All-cause mortality is reported for the Full Analysis Set (all randomized patients; Arm A=246 patients, Arm B=249 patients). Adverse Events are reported for the Safety Analysis Set (all patients who received at least one or partial dose of melflufen, pomalidomide, or dexamethasone; Arm A=228 patients, Arm B=246 patients). Non-serious AEs were not calculated in this study. Data reported in the "Other Adverse Events" section include all TEAEs (non-serious AEs and serious AEs).

Melflufen 40 mg i.v. on Day 1 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Melflufen: Intravenous infusion

Dexamethasone: Oral tablets

Arm A: Melflufen+Dexamethasone

Pomalidomide 4 mg orally daily on Days 1 to 21 and dexamethasone 40 mg (20 mg for patients ≥ 75 years of age) on Days 1, 8, 15 and 22 of each 28-day cycle. Patients were to be treated until confirmed progression, unacceptable toxicity, or the patient or investigator decided it was not in the patient's best interest to continue.

Pomalidomide: Oral capsules

Dexamethasone: Oral tablets

Arm B: Pomalidomide+Dexamethasone

Age, Categorical

Romania

Hungary

Czechia

United States

United Kingdom

Spain

Russia

Greece

Netherlands

Austria

South Korea

Belgium

Norway

Taiwan

Denmark

Poland

Italy

Israel

France

Lithuania

Estonia

Region of Enrollment

All patients that were enrolled defined as patients assigned a unique patient number by Interactive Response Technology system at the time of enrollment.

Chief Operating Officer

All randomized patients (Full Analysis Set as per protocol) were included into the primary outcome measure analysis.

Full Analysis Set (all patients randomized to either Arm A or Arm B).

Safety Analysis Set (all patients that have received at least one dose of study drug in either Arm A or Arm B).

Safety and Tolerability: Number of Patients With Treatment-emergent Adverse Events (TEAEs), Including Clinical Laboratory and Vital Signs Abnormalities, as Assessed by CTCAE v4.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Melflufen (Melphalan Flufenamide) in Combination With Daratumumab in Relapsed-Refractory Multiple Myeloma	NCT04649060	Relapsed Multip... Relapsed-Refrac...	Melflufen Dexamethasone Daratumumab	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide	NCT03151811	Multiple Myelom...	Melflufen Pomalidomide Dexamethasone	18 Years -	Oncopeptides AB
A Study of Melphalan Flufenamide (Melflufen)-Dex or Pomalidomide-dex for RRMM Patients Refractory to Lenalidomide	NCT03151811	Multiple Myelom...	Melflufen Pomalidomide Dexamethasone	18 Years -	Oncopeptides AB

Spots Global Cancer Trial Database for melflufen

Every month we try and update this database with for melflufen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for melflufen

Every month we try and update this database with for melflufen cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for melflufen cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.