Study of Daratumumab in Combination With Dexamethasone in Resistant or Refractory Multiple Myeloma

NCT02626481 | Completed Phase 2 DMC

• 2 other identifiers: 2015_292015-002221-19
• Study Type: interventional
• Target: 64
• Locations: 2 countries
• Sites: 41

Brief Summary

This study is a Multicentre, Open-label, Phase II study of Daratumumab and Dexamethasone in MM patients. Eligible patients must have a symptomatic RRMM with a measurable disease, resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide. There is no dose escalation phase, as the MAxiamal Tolerated Dose (MTD) and drug scheduling have already been determined in previous phase 1-2 dose escalation studies. There is no randomization.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Cancer; refractory; daratumumab

Outcome Measures

Primary Outcomes (1)

• Number of best Overall Response using the IMWG response criteria

  best Overall Response Rate (ORR, PR or better) using the IMWG response criteria.

  60 months

Secondary Outcomes (3)

• Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

  60 months

• Number of patients who reach Very Good Partial Response and Complete using IMWG response criteria

  60 months

• Rate of Overall Survival (OS)

  60 months

Study Arms (1)

Daratumumab + Dexamethasone

EXPERIMENTAL

patients treated with Daratumumab (16 mg/kg) and Dexamethasone (40 or 20 mg regarding age of patient)

Drug: Daratumumab; Drug: Dexamethasone

Interventions

Daratumumab DRUG

patients treated with Daratumumab (16 mg/kg) and Dexamethasone (40 or 20 mg regarding age of patient)

Also known as: Experimental Arm

Daratumumab + Dexamethasone

Dexamethasone DRUG

patients treated with Dexamethasone (40 or 20 mg regarding age of patient)

Also known as: Experimental Arm

Daratumumab + Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be able to understand and voluntarily sign an informed consent form
• Must be able to adhere to the study visit schedule and other protocol requirements
• Age ≥18 years
• Life expectancy \> 6 months
• Patients must have relapsed myeloma, and previously treated with Bortezomib, Lenalidomide, and Pomalidomide treatment, and being resistant or refractory to Bortezomib and Lenalidomide and Pomalidomide treatment, defined as follows:
• Any number of prior therapies 5.2. Patients must have Progressive Disease as defined by the IMWG as one of the following (Kyle, 2009):
• Increase of 25% from lowest response value in any one or more of the following:
• Serum M-component (absolute increase must be ≥ 0.5 g/100 ml)b and/or Urine M-component (absolute increase must be ≥ 200 mg per 24 h) and/or
• Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved
• FLC levels (absolute increase must be \> 10 mg/l). Bone marrow plasma cell percentage (absolute % must be ≥ 10%)
• Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
• Development of hypercalcemia (corrected serum calcium \> 11.5 mg/100 ml) that can be attributed solely to the plasma cell proliferative disorder 5.3. Patients must have undergone prior treatment with Bortezomib and Lenalidomide and Pomalidomide:
• They must have received at least two cycles of therapy
• Either at diagnosis or relapse
• Either in separate regimens or within the same regimen

You may not qualify if:

• Target disease exceptions:
• Solitary bone/solitary extramedullary plasmocytoma
• Patients with non-secretory MM and non-measurable MM
• Evidence of central nervous system (CNS) involvement
• Medical history and Concurrent disease:
• o Subjects with prior (≤ 5 years) or concurrent invasive malignancies except the following: Adequately treated basal cell or squamous cell skin cancer Incidental finding of low grade (Gleason 3+3 or less) prostate cancer Any cancer from which the subject has been disease free for at least 3 years.
• Subject with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (ie: uncontrolled diabetes or uncontrolled coronary artery disease)
• Any uncontrolled or severe cardiovascular or pulmonary disease determined by the investigator including:
• NYHA functional classification III or IV congestive heart failure LVEF ( Left Ventricular Ejection Fraction) ≥45% Uncontrolled angina, hypertension or arrhythmia Myocardial infarction in the past 6 months
• Subjects with grade 2 or greater peripheral neuropathy (as per NCI-CTCAEv4.0)
• Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen. Or, subject is a man who plans to father a child while enrolled in this study or within 4 months after the last dose of any component of the treatment regimen.
• Known positive for HIV or active hepatitis B or C.
• Subjects with psychiatric illnesses or social situations that would preclude them understanding the informed consent, study compliance or the ability to tolerate study procedures and/or study therapy
• Subjects with known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 \<50% of predicted normal.
• Subjects with a history of moderate or severe persistent asthma within the past 2 years (see appendix), or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study).

Sponsors & Collaborators

• University Hospital, Lille: lead
• Janssen, LP: collaborator
• Intergroupe Francophone du Myelome: collaborator

Study Sites (41)

AZ ST Jan hematology department

Bruges, 8000, Belgium

Location

Hematologie Laarbeeklaan

Brussels, 101 - 1090, Belgium

Location

Jules Bordet Institute

Brussels, B - 1000, Belgium

Location

CHU Dinant Godinne | UCL Namur asbl

Yvoir, 1 - 5530, Belgium

Location

CHRU - Hôpital du Bocage (Amiens)

Amiens, 49033, France

Location

CHRU-Hôpital Sud d'Amiens

Amiens, 80054, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

Polyclinique Bordeaux Nord Aquitaine

Bordeaux, 33300, France

Location

Hôpital du Haut Lévêque Centre François Magendie

Bordeaux, 33604, France

Location

Clinique - ICH CHU de Brest Hôpital Morvan

Brest, 29609, France

Location

CHRU Côte de Nacre

Caen, 14033, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Hôpital d'instruction des armées Percy

Clamart, 92141, France

Location

Hématologie Clinique CHU DIJON

Dijon, 21000, France

Location

Centre Hospitalier Général

Dunkirk, 59 385, France

Location

CHRU, Hôpital A.Michallon

Grenoble, 38043, France

Location

Médecine interne Centre hospitalier départemental

La Roche-sur-Yon, 85025, France

Location

Service d'Hématologie CHV André Mignot

Le Chesnay, 78157, France

Location

CHRU , Hôpital Claude Huriez

Lille, France

Location

Sce Hématologie Thérapie Cellulaire CHU Limoges

Limoges, 87000, France

Location

Institut Paoli Calmette

Marseille, 13273, France

Location

Hopital J Monod Sce Rhumato Nord

Montivilliers, 76290, France

Location

Service Hématologie CHRU Montpellier

Montpellier, 34090, France

Location

Hopital E Muller

Mulhouse, 68100, France

Location

Maladies du sang CHRU Hôtel Dieu

Nantes, 44035, France

Location

URC/CIC Paris Descartes Necker-Cochin

Paris, 75015, France

Location

Curie Institut

Paris, 75248, France

Location

Hôpital Saint-Louis

Paris, 75475, France

Location

CHU - Hôpital St Antoine

Paris, 75571, France

Location

Unité de Recherche Clinique - CH Périgueux

Périgueux, 24019, France

Location

Centre Hospitalier Lyon sud

Pierre-Bénite, 69495, France

Location

CHU de la milétrie

Poitiers, 86000, France

Location

Hôpital R.Debré

Reims, 51032, France

Location

Hôpital de Pontchaillou

Rennes, 35033, France

Location

Service Hématologie Centre Hospitalier Yves le Foll

Saint-Brieuc, 22000, France

Location

Service d'Hématologie Clinique Institut de Cancérologie Lucien Neuwirth

Saint-Priest-en-Jarez, 42270, France

Location

Département d'Hématologie et Oncologie Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Hématologie CHRU IUCT Oncopole

Toulouse, 31100, France

Location

Onco-hématologie CHRU Hôpital Bretonneau

Tours, 37044, France

Location

Hôpitaux de Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

service hématologie CH Bretagne Atlantique

Vannes, 56017, France

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms

Interventions

daratumumab; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Thierry Facon, MD, PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 16, 2015
• First Posted: December 10, 2015
• Study Start: December 28, 2015
• Primary Completion: March 9, 2020
• Study Completion: March 9, 2020
• Last Updated: March 26, 2021

Record last verified: 2021-03

Locations

FR (37); BE (4)