FUSIONMM-003: A Study to Determine the Safety and Efficacy for the Combination of Durvalumab and Daratumumab in Relapsed and Refractory Multiple Myeloma

Sponsor

Celgene (Industry)

Overall Status

Completed

CT.gov ID

NCT02807454

Collaborator

(none)

Enrollment

Locations

Arms

65.9

Actual Duration (Months)

0.8

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Daratumumab Drug: Durvalumab Drug: Pomalidomide Drug: Dexamethasone	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Jul 7, 2016

Actual Primary Completion Date :

Jan 3, 2022

Actual Study Completion Date :

Jan 3, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Daratumumab Plus Durvalumab Treatment Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward	Drug: Daratumumab Drug: Durvalumab
Experimental: Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward oral POM at 4mg/day on days 1 to 21 oral/IV dex at 40mg/day (>75 years old) or 20mg/day (>75 years old) on days 1, 8, 15 and 22	Drug: Daratumumab Drug: Durvalumab Drug: Pomalidomide Drug: Dexamethasone

Arm

Intervention/Treatment

Experimental: Daratumumab Plus Durvalumab Treatment

Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward

Drug: Daratumumab

Drug: Durvalumab

Experimental: Pomalidomide+ Daratumumab+ Durvalumab+ Dexamethasone Treatment

Intravenous (IV) durvalumab at 1500mg on Day 1 or 2 of a 28-day cycle IV daratumumab at 16mg/kg on days 1, 8, 15 and 22 at cycles 1-2; on days 1 and 15 at cycles 3-6; and on day 1 from cycle 7 onward oral POM at 4mg/day on days 1 to 21 oral/IV dex at 40mg/day (>75 years old) or 20mg/day (>75 years old) on days 1, 8, 15 and 22

Drug: Daratumumab

Drug: Durvalumab

Drug: Pomalidomide

Drug: Dexamethasone

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) [Up to approximately 1.5 years]
Defined as tumor response (including progressive disease), based on the investigator assessments according to the International Myeloma Working Group (IMWG) Uniform Response Criteria
Adverse Events (AEs) [Up to approximately 1.5 years]
Number of participants with adverse events

Secondary Outcome Measures

Time to response (TTR) [up to approximately 1.5 years]
Time from enrollment to the first documentation of response (Partial Response [PR] or greater)
Duration of Response (DOR) [up to approximately 2.5 years]
Time from the first documentation of response (PR or greater) to the first documentation of Progressive disease (PD)
Progression-free Survival (PFS) [up to approximately 2 years]
Time from enrollment to the first documentation of PD or death from any cause during study, whichever occurs earlier
Pharmacokinetics- Cmax [up to approximately 2 years]
Maximum observed concentration
Pharmacokinetics- AUC [up to approximately 2 years]
Area under the concentration-time curve
Pharmacokinetics- Tmax [up to approximately 2 years]
Time to maximum concentration
Pharmacokinetics- t1/2 [up to approximately 2 years]
Terminal elimination half-life
Pharmacokinetics- CL/F [up to approximately 2 years]
Apparent total body clearance
Pharmacokinetics- Vz/F [up to approximately 2 years]
Apparent volume of distribution

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	UCLA Division of Hematology Oncology	Los Angeles	California	United States	90095-1752
3	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
4	Emory University Hospital	Atlanta	Georgia	United States	30322
5	University of Chicago Medical Center	Chicago	Illinois	United States	60637
6	Center For Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
7	Dana-Farber Partners Cancer Care, Inc.	Boston	Massachusetts	United States	02115
8	Washington University	Saint Louis	Missouri	United States	63110
9	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
10	Perelman Center for Advanced Medicine	Philadelphia	Pennsylvania	United States	19104
11	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
12	Swedish Medical Center	Seattle	Washington	United States	98104
13	AZ St-Jan Brugge Oostende AV	Brugge		Belgium	8000
14	Universitaire Ziekenhuizen Leuven Univeristy Hospitals Leuven	Leuven		Belgium	B-3000
15	Cliniques Universitaires UCL de Mont-Godine	Yvoir		Belgium	5530
16	Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 3L6
17	Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
18	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada	H1T 2M4
19	MUHC Glen Site	Montreal	Quebec	Canada	H4A 3J1
20	Rigshospitalet University Hospital	Copenhagen		Denmark	2100
21	Odense University Hospital	Odense		Denmark	DK-5000
22	Vejle Hospital	Vejle		Denmark	7100
23	Universitatsklinikum Carl Gustav Carus an der TU Dresden	Dresden		Germany	01307
24	Universitatsklinikum Heidelberg	Heidelberg		Germany	69115
25	University Hospital Tubingen	Tubingen		Germany	72076
26	Universitatsklinikum Wuerzburg	Wuerzburg		Germany	97080
27	Policlinico S. Orsola - Malpighi	Bologna		Italy	40138
28	A.O.U. Maggiore della Carità	Novara		Italy	28100
29	Azienda Ospedaliera di Padova	Padova		Italy	35128
30	Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello	Palermo		Italy	90146
31	A.O. Universitaria Ospedale S.Chiara Dip.Oncologia, Div. Ematologia	Pisa		Italy	56126
32	Hospital Durán i Reynals - Instituto Catalàn de Oncologìa ICO	Barcelona		Spain	08907
33	Local Institution - 453	Barcelona		Spain	08907
34	Hospital de Cabuenes	Gijon		Spain	33394
35	Hospital Universitario Fundacion Jimenez Diaz	Madrid		Spain	28040
36	Hospital 12 de Octubre	Madrid		Spain	28041
37	Sahlgrenska University Hospital	Gothenburg		Sweden	60 Gothenburg
38	Skanes Universitetssjukhus Malmo	Lund		Sweden	221 85
39	Karolinska Universitetssjukhuset - Huddinge	Stockholm		Sweden	SE-14186
40	St. Bartholomew's and The Royal London Hospital	London		United Kingdom	EC1A 7BE
41	Christie Hospital	Manchester		United Kingdom	M20 4BX
42	Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine	Oxford		United Kingdom	0X3 7LE
43	Royal Marsden Hospital	Sutton (Surrey)		United Kingdom	SM2 5PT
44	The Royal Wolverhampton Hospital NHS Trust	Wolverhampton		United Kingdom	WV10 0QP