A study to determine the effectiveness for the combination of durvalumab and daratumumab (D2) to treat relapsed and refractory multiple myeloma in subjects whose multiple myeloma has worsened while on a daratumumab therapy as their last multiple myeloma treatment.

Phase 1

• Conditions: Relapsed and Refractory Multiple Myeloma; MedDRA version: 19.1Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-003801-32-GR
• Lead Sponsor: Celgene International II Sàrl

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-02-21
• Last Update Posted: 29 January 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Subject received at least 3 prior anti-myeloma regimens including a 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.
2. All subjects must have failed DARA either as a single agent or in combination on last MM therapy. Failure is defined as PD on DARA either as a single agent or in combination.
3. Subject has measurable disease defined as:
a. M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis (uPEP): sPEP = 0.5 g/dL or uPEP = 200 mg/24 hours) and/or
b. 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
4. Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen.
5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2 or less.
6. Subject’s toxicities resulting from previous therapy (including peripheral neuropathy) have resolved or stabilized to = Grade 1.
7. Subject is at least 18 years of age at the time of signing the informed consent form (ICF).
8. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
9. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
10. 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.
Note: Pregnancy testing does not need to be repeated prior to Cycle 1 if the serum pregnancy test for screening was performed within 72 hours of the first dose 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, injectable, 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 DARA or DURVA, whichever is later.
d. Refrain from

Exclusion Criteria

1. Subject has had prior exposure to anti-CTLA-4, anti-PD-1, anti-PD-L1 mAbs, or cancer vaccines
2. Subject has received ASCT within 12 weeks before the date of randomization.
3. History of organ or allogeneic stem cell transplantation
4. Subject received any of the following within the last 14 days of initiating study treatment:
a. Plasmapheresis
b. Major surgery
c. Radiation therapy other than local therapy for myeloma associated bone lesions
d. Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in combination with other agents given with it)
5. Subject received prior treatment with a monoclonal antibody within 5 half-lives of initiating study treatment, other than DARA.
6. Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment.
7. Subject has any of the following laboratory abnormalities:
a. ANC < 1,000/µL
b. Platelet count: < 75,000/µL (it is not permissible to transfuse a subject to reach this level)
c. Hemoglobin < 8 g/dL (< 4.9 mmol/L)(it is not permissible to transfuse a subject to reach this level)
d. Creatinine clearance (CrCl) < 45 mL/min (calculated using the Cockcroft-Gault formula or directly calculated from the 24-hour urine collection method)
e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
f. AST or ALT > 2.5 × ULN
g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with documented Gilbert’s syndrome
8. Subject has clinical evidence of CNS or pulmonary leukostasis, disseminated intravascular coagulation, or CNS MM
9. Subject has known COPD with a 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.
10. 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.
11. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or amyloidosis
12. Subject has nonsecretory MM
13. Subject has known allergy or hypersensitivity to study drug formulations
14. Subject has active or prior documented autoimmune or inflammatory disorders within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
a. Subjects with vitiligo or alopecia.
b. Subjects with hypothyroidism (eg, following Hashimoto’s disease) stable on hormone replacement.
c. Psoriasis not requiring systemic treatment.
15. Subject has history of primary immunodeficiency
16. Subject is positive for HIV-1, chronic or active hepatitis B or active hepatitis A or C.
17. Subject has received live, attenuated vaccine within 30 days prior to the first dose of DURVA.
18. Subject is currently using or has used immunosuppressive medication within 14 days prior to the first study dose of study treatment. The following are exceptions to this criterion:
a. Intranasal, topical, inhaled, or local steroid injections (eg, intra-articular injection).
b. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.
c. Steroids as premedication for hypersensitivity reactions (eg, infusion-related reactions, computed tomography [CT] scan premedication).
19. Subject has any one of the following:
a. Clinically significant ab

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified