A Study to Determine the Efficacy of the Combination of Daratumumab (DARA) Plus Durvalumab (DURVA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)

Completed · Phase 2

Conditions studied: Multiple Myeloma

In brief

This is a single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the combination regimen of daratumumab plus durvalumab (D2). The study will consist of 2 parts; Part 1 has a 2-stage design while Part 2 consists of an expansion phase. Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly \[QW\], every 2 weeks \[Q2W\] or every 4 weeks \[Q4W\] of each 28-day cycle) received on their last prior therapy containing DARA. The dosing schedule for DARA may be adjusted during the course of the study as outlined in the protocol. Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.

Key facts

Study ID

NCT03000452

Run by

Celgene

People needed

18

Starts

2017-03-14

Expected to finish

2017-12-04

Last updated by the study team

2018-10-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject received at least 3 prior anti-myeloma regimens including a proteasome inhibitor (PI) and an immunomodulatory agent or is double-refractory to a PI and an immunomodulatory agent.
• Induction, bone marrow transplant with or without maintenance therapy is considered one regimen.
• Refractory is defined as disease that is nonresponsive on therapy, or progresses within 60 days of last therapy. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
• For subjects who received more than 1 regimen containing a PI their disease must be refractory to the most recent PI containing regimen.
• For subjects who received more than 1 regimen containing a immunomodulatory agent their disease must be refractory to the most recent immunomodulatory agent containing regimen.
• All subjects must have failed Daratumumab (DARA) either as a single agent or in combination on last Multiple myeloma (MM) therapy. Failure is defined as disease progression(PD) on DARA either as a single agent or in combination.
• Subject has measurable disease defined as:
• M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis (uPEP): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours) and/or
• Light chain MM without measurable disease in the serum or the urine: serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2 or less.
• Subject's toxicities resulting from previous therapy (including peripheral neuropathy) have resolved or stabilized to ≤ Grade 1.
• Subject is at least 18 years of age the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Females of childbearing potential (FCBP) must:
• a. Have 2 negative pregnancy tests as verified by the investigator prior to starting study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
• i. Negative serum pregnancy test at screening ii. Negative serum or urine pregnancy test (investigator's discretion) within 72 hours prior to starting study treatment (Cycle 1, Day 1), and before beginning each subsequent cycle of treatment, and after end of study treatment.
• b. Either practice true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption (eg, oral, inject able, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; true abstinence; or vasectomized partner), 28 days prior to starting study treatment, during the study therapy (including dose interruptions), and for at least 90 days after discontinuation of study treatment.
• c. Agree to abstain from breastfeeding during study participation and for at least 90 days after the last dose of Daratumumab (DARA) or Durvalumab (DURVA), whichever is later.
• d. Refrain from egg cell donation for at least 90 days after the final dose of DURVA or DARA, whichever is later.
• Male subjects must:
• Either practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 90 days following study treatment discontinuation, even if he has undergone a successful vasectomy.
• Refrain from sperm donation for at least 90 days after the final dose of DURVA or DARA, whichever is later.

You may not qualify if…

• The presence of any of the following will exclude a subject from enrollment:
• Subject has had prior exposure to anti-CTLA-4, anti-PD-1 (Programmed cell death-1), anti-PD-L1 (Programmed death-ligand 1) Monoclonal antibody (mAbs), or cancer vaccines
• Subject has received autologous stem cell transplantation (ASCT) within 12 weeks before the date of randomization.
• History of organ or allogeneic stem cell transplantation
• Subject received any of the following within the last 14 days of initiating study treatment:
• Plasmapheresis
• Major surgery (as defined by the investigator)
• Radiation therapy other than local therapy for myeloma associated bone lesions
• Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in combination with other agents given with it)
• Subject received prior treatment with a monoclonal antibody within 5 half-lives of initiating study treatment, other than DARA.
• Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
• Subject has any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) < 1,000/µL
• Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level)
• Hemoglobin < 8 g/dL (< 4.9 mmol/L) (it is not permissible to transfuse a subject to reach this level)
• Creatinine clearance (CrCl) < 45 mL/min (calculated using the Cockcroft-Gault formula or directly calculated from the 24-hour urine collection method)
• Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
• Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × upper limit of normal (ULN)
• Serum total bilirubin > 1.5 × upper limit of normal (ULN) or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
• Subject has clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS MM
• Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal. Note that forced expiratory testing (FEV1) is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is < 50% of predicted normal.
• Subject has known moderate or severe persistent asthma within the past 2 years or uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study.
• Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or amyloidosis
• Subject has nonsecretory MM
• Subject has known allergy or hypersensitivity to study drug formulations

Where it is running

• City of Hope Cancer Center — Duarte, California, United States
• Cancer Center of Central Connecticut — Southington, Connecticut, United States
• Parkview Research Center — Fort Wayne, Indiana, United States
• Indiana University Cancer Center — Indianapolis, Indiana, United States
• University of Kansas Hospital — Westwood, Kansas, United States
• University of Maryland School of Med — Baltimore, Maryland, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• John Theurer Cancer Center at Hackensack University Medical Center — Hackensack, New Jersey, United States
• Morristown Memorial Hosp — Morristown, New Jersey, United States
• OHSU — Portland, Oregon, United States
• MD Anderson Cancer Center — Houston, Texas, United States
• Universitaetsklinik Innsbruck — Innsbruck, Austria
• Salzburger Landkliniken St. Johanns-Spital — Salzburg, Austria
• Medizinische Universitat Wien — Vienna, Austria
• Alexandra General Hospital of Athens — Athens, Greece
• UMCU Utrecht — Utrecht, Netherlands
• Hospital Universitari Germans Trias i Pujol Can Ruti — Badalona (Barcelona), Spain
• Hospital Universitario Ramon y Cajal — Madrid, Spain
• Hospital Universitario de Salamanca — Salamanca, Spain
• Hospital Universitario Dr. Pesset — Valencia, Spain
• Falu lasarett — Falun SE, Sweden
• Helsingborg hospital — Helsingborg, Sweden
• Lund University Hosptial — Lund, Sweden
• Karolinska University Hospital Huddinge — Stockholm, Sweden

Full record on ClinicalTrials.gov

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