A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

— FUSIONMM-003  

Official title:

A Phase 2, Multicenter, Open-label, Study to Determine the Safety and Efficacy for the Combination of Durvalumab (DURVA) and Daratumumab (DARA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02807454
• Other study ID #: MEDI4736-MM-003
• Status: Terminated
• Phase: Phase 2
• Start date: July 7, 2016
• Est. completion date: January 3, 2022

Study information

• Verified date: February 2023
• Source: Celgene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter study to confirm the safety and efficacy of durvalumab + daratumumab (D2) in subjects with relapsed and refractory multiple myeloma. This study will also explore the safety and efficacy of the addition of pomalidomide + dexamethasone to durvalumab + daratumumab (PD3).

On 05 Sep 2017, a Partial Clinical Hold was placed on this study by the United States (US) Food and Drug Administration (FDA). The decision by the FDA was based on data related to risks of anti-programmed cell death-1 (PD-1) antibody, pembrolizumab, in combination with IMiDs® immunomodulatory drugs in patients with multiple myeloma. As a result, enrollment into this study has been discontinued. Subjects who are receiving clinical benefit, based on the discretion of the investigator, may remain on study treatment after being reconsented.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: January 3, 2022
• Est. primary completion date: January 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must have measurable disease as defined by m-protein or serum free light chain.

• Must have failed last line of treatment (refractory to last line of treatment).

• Must have achieved at least a minimal response (MR) to at least 1 prior anti-myeloma regimen before developing PD (relapsed)

• Has performance status of 0, 1, or 2 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

• Must be at least 18 years of age

Exclusion Criteria:

• Has non-secretory multiple myeloma

• Has had prior anti-myeloma therapy within 2 weeks prior to study Day 1

• Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways).

• Has received prior treatment with daratumumab or other anti-CD38 therapies previously

• Has undergone prior organ or allogeneic hematopoetic stem cell transplantation

• Has received autologous stem cell transplantation (ASCT) within 12 weeks before the date of randomization.

• Has received prior treatment with a monoclonal antibody within 5 half-lives of Study Day 1

• Has received investigational agents within 28 days or 5 half-lives (whichever is longer) of Study Day 1

• Has received live, attenuated vaccine within 30 days prior to Study Day 1

• Has chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal

• Has moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification.

• Is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B or active hepatitis A or C

• Has a prior history of malignancies, other than MM, unless the subject has been free of the disease for = 5 years (with the exception Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer [T1a or T1b] or prostate cancer that is curative)

• Has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma

• Has clinically significant cardiac disease

• Is a female who is pregnant, nursing, or breastfeeding, or who intends to become pregnant during the participation in the study

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab

• Durvalumab

• Pomalidomide

• Dexamethasone

Locations

Country	Name	City	State
Belgium	AZ St-Jan Brugge Oostende AV	Brugge
Belgium	Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven	Leuven
Belgium	Cliniques Universitaires UCL de Mont-Godine	Yvoir
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Local Institution - 101	Montreal	Quebec
Canada	MUHC Glen Site	Montreal	Quebec
Canada	Local Institution - 103	Saint John	New Brunswick
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	Local Institution - 104	Toronto	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Denmark	Local Institution - 552	Copenhagen
Denmark	Rigshospitalet University Hospital	Copenhagen
Denmark	Local Institution - 553	Odense
Denmark	Odense University Hospital	Odense
Denmark	Local Institution - 551	Vejle
Denmark	Vejle Hospital	Vejle
Germany	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden
Germany	Local Institution - 203	Heidelberg
Germany	Universitatsklinikum Heidelberg	Heidelberg
Germany	University Hospital Tubingen	Tubingen
Germany	Local Institution - 201	Wuerzburg
Germany	Universitatsklinikum Wuerzburg	Wuerzburg
Italy	Local Institution - 354	Bologna
Italy	Policlinico S. Orsola - Malpighi	Bologna
Italy	A.O.U. Maggiore della Carità	Novara
Italy	Local Institution - 353	Novara
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Local Institution - 355	Padova
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello	Palermo
Italy	A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia	Pisa
Spain	Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO	Barcelona
Spain	Local Institution - 453	Barcelona
Spain	Hospital de Cabuenes	Gijon
Spain	Local Institution - 451	Gijon
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Local Institution - 452	Madrid
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Local Institution - 501	Lund
Sweden	Skanes Universitetssjukhus Malmo	Lund
Sweden	Karolinska Universitetssjukhuset - Huddinge	Stockholm
Sweden	Local Institution - 502	Stockholm
United Kingdom	St. Bartholomew's and The Royal London Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Local Institution - 252	Oxford
United Kingdom	Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine	Oxford
United Kingdom	Local Institution - 253	Sutton (Surrey)
United Kingdom	Royal Marsden Hospital	Sutton (Surrey)
United Kingdom	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton
United States	Emory University Hospital	Atlanta	Georgia
United States	Center For Cancer and Blood Disorders	Bethesda	Maryland
United States	Dana-Farber Partners Cancer Care, Inc.	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Local Institution - 007	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	UCLA Division of Hematology Oncology	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Tennessee Oncology Nashville Drug Development Unit	Nashville	Tennessee
United States	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	University of Pennsylvania - Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania
United States	Washington University	Saint Louis	Missouri
United States	Swedish Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Celgene

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Denmark,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. ORR was calculated as the percent of responders (multiplied by 100). Partial response required = 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by = 90% or to < 200 mg per 24 hours.	From first dose to up to approximately 66 months
Primary	Number of Participants With Adverse Events (AEs)	Number of participants who experienced at least one adverse event. An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values, regardless of etiology. Any worsening (i.e., any clinically significant adverse change in the frequency or intensity of a preexisting condition should be considered an AE.	From first dose to 90 days after last dose (up to approximately 58 months)
Primary	Number of Participants With Serious Adverse Events (SAEs)	Number of participants who experienced at least one serious adverse event. An SAE is any AE occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, constitutes an important medical event.	From first dose to 90 days after last dose (up to approximately 58 months)
Secondary	Time-To-Response (TTR)	Time-to-response is calculated as the time from enrollment to the first date of documented response (partial response or better). Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required = 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by = 90% or to < 200 mg per 24 hours. For those participants where POM + DEX were added, time-to-response was calculated from the date POM and DEX were added to the first date of documented response (PR or better).	From enrollment to earliest documented response (up to approximately 66 months)
Secondary	Kaplan-Meier Estimate of Duration of Response (DOR) - Simon Stage 1: D2 Arm	Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required = 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by = 90% or to < 200 mg per 24 hours. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be = 0.5 g/dL) and/or urine M-component (absolute increase must be = 200 mg/24 h).	From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
Secondary	Kaplan-Meier Estimate of Duration of Response (DOR) - PD3 Arm	Duration of response was calculated as the time from the earliest date of documented response (PR or better) to the earliest date of disease progression as determined by the investigator. For those participants where POM + DEX was added, duration of response was calculated as the time from the earliest date of documented response after POM + DEX was added (PR or better) to the earliest date of disease progression as determined by the investigator. Participants who are alive or lost to follow-up will be censored on the last-known-to-be-alive date. Tumor response of partial response (PR) or better was assessed using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Partial response required = 50% reduction of serum M-Protein and reduction in 24-hour urinary M protein by = 90% or to < 200 mg per 24 hours.	From the earliest date of documented response (PR or better) to earliest date of progressive disease (up to approximately 66 months)
Secondary	Kaplan-Meier Estimate of Progression-Free Survival (PFS) - Simon Stage 1: D2 Arm	Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be = 0.5 g/dL) and/or urine M-component (absolute increase must be = 200 mg/24 h).	From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
Secondary	Kaplan-Meier Estimate of Progression-Free Survival (PFS) - PD3 Arm	Progression-free survival was calculated as the time between the enrollment to the first documentation of progressive disease or death from any cause during study, whichever occurs earlier using the International Myeloma Working Group (IMWG) Uniform Response Criteria. Progressive Disease required increase of 25% from lowest response value in the serum M-component (absolute increase must be = 0.5 g/dL) and/or urine M-component (absolute increase must be = 200 mg/24 h).	From enrollment to first documentation of progressive disease or death from any cause during study, whichever occurs earlier (up to approximately 66 months)
Secondary	Maximum Observed Plasma Concentration (Cmax) - Simon Stage 1: D2 Arm	Pharmacokinetics of Durvalumab derived from serum concentration versus time data.	Cycle 1 - Days 2, 8, 15, 22
Secondary	Time of Maximum Observed Concentration (Tmax) - Simon Stage 1: D2 Arm	Pharmacokinetics of Durvalumab derived from serum concentration versus time data.	Cycle 1 - Days 2, 8, 15, 22
Secondary	Area Under the Plasma Concentration-Time Curve to the Last Measurable Plasma Concentration [AUC(0-Last)] - Simon Stage 1: D2 Arm	Pharmacokinetics of Durvalumab derived from serum concentration versus time data.	Cycle 1 - Days 2, 8, 15, 22
Secondary	Area Under the Plasma Concentration-Time Curve in 1 Dosing Interval [AUC(TAU)] - Simon Stage 1: D2 Arm	Pharmacokinetics of Durvalumab derived from serum concentration versus time data.	Cycle 1 - Days 2, 8, 15, 22

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting