A phase 1B multicenter, open-label study to determine the recommended dose and regimen of Durvalumab (MEDI4736) either as monotherapy or in combination with Pomalidomide (POM) with or without low-dose Dexamethasone (DEX) in subjects with relapsed and refractory multiple myeloma (RRMM)
- Conditions
- Multiple myeloma - bone marrow cancer10035227
- Registration Number
- NL-OMON53145
- Lead Sponsor
- Celgene Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 15
1. Subject is >= 18 years of age at the time of signing the informed consent
form (ICF).
2. Subject must understand and voluntarily sign an ICF prior to any
study-related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other
protocol requirements.
4. Subject has documented diagnosis of multiple myeloma and have measurable
disease by serum protein electrophoresis (sPEP) or urine protein
electrophoresis (uPEP): sPEP >= 0.5 g/dL or uPEP >= 200 mg/24 hours (except for
subjects in the EMP sub-group).
5. Subject had at least 2 prior anti-myeloma regimens.
(Note: Induction, bone marrow transplant with or without maintenance therapy is
considered one regimen.)
6. Subject achieved at least a stable disease (SD) for at least 1 cycle of
treatment to at least 1 prior anti-myeloma regimen before developing PD.
7. Subject had documented PD during or within 60 days after the last
anti-myeloma regimen.
8. Subject received prior treatment with a lenalidomide-containing regimen for
at least 2 consecutive cycles.
9. Subject received prior treatment with a proteasome inhibitor-containing
regimen for at least 2 consecutive cycles.
10. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status
of 0, 1, or 2.
11. Females of childbearing potential (FCBP ) must:
a. Have 2 negative pregnancy tests as verified by the investigator prior to
starting study treatment. She must agree to ongoing pregnancy testing during
the course of the study, and after end of study treatment. This applies even if
the subject practices true abstinence from heterosexual contact.
b. Either practice true abstinence2 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, 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. Refrain from egg cell donation for at least 90 days after the final dose of
durvalumab
12. Male subjects must:
a. Either practice true abstinence2 (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.
b. Refrain from sperm donation for at least 90 days after the final dose of
durvalumab
For subjects who will be in the Arm C extramedullarly plasmacytoma subgroup,
the following includsion criterium will also apply:
13. Subject has radiologically measurable EMP disease (soft tissue of bone
related) that is amenable to biopsy and subject agrees and consents to
additional biopsy procedures as described in the protocol. These subjects do
not need to have measurable disease by sPEP and/or uPEP.
1. Subject has any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the subject from participating in the
study
2. Subject has any condition including the presence of laboratory
abnormalities, which places the subject at unacceptable risk if he/she were to
participate in the study
3. Subject has any condition that confounds the ability to interpret data from
the study
4. Subject has non-secretory or oligosecretory multiple myeloma (uitzondering
voor patienten in de EMP sub-groep.
5. Subject has any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) < 1,000/µL
b. Platelet count: < 75,000/µL
c. Hemoglobin < 8 g/dL (< 4.9 mmol/L)
d. Creatinine Clearance (CrCL) < 45 mL/min
e. Corrected serum calcium > 13.5 mg/dL (> 3.4 mmol/L)
f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >
2.5 × ULN
g. Serum total bilirubin > 1.5 × ULN or > 3.0 mg/dL for subjects with
documented Gilbert*s syndrome
6. Subject has prior history of malignancies, other than MM, unless the subject
has been free of the disease for >= 5 years with the exception of the following
non-invasive malignancies:
• 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 using the TNM
[tumor, nodes, metastasis] clinical staging system) or prostate cancer that is
curative
7. Subject had prior treatment with POM but did not achieve at least a SD with
the POM-containing regimen
8. Subject had prior exposure to immunotherapy, including, but not limited to,
other anti-CTLA-4,anti-PD-1, anti-PD-L1 mAbs, cell-based therapies, or cancer
vaccines
9. Subject has history of organ or allogeneic stem cell transplantation
10. Subject has or had clinical evidence of central nervous system (CNS) or
pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple
myeloma
11. Subject has history of anaphylaxis or hypersensitivity to thalidomide,
lenalidomide, POM, or dex
12. Subject had rash >= Grade 3 during prior thalidomide, lenalidomide, or POM
therapy
13. Subject has incidence of gastrointestinal disease that may significantly
alter the absorption of POM
14. Subject has known or suspected hypersensitivity to the excipients
contained in the formulation of durvalumab, POM, or dex
15. Subject has received any of the following within the last 14 days of
initiating study treatment:
a. Plasmapheresis
b. Major surgery (as defined by the investigator)
c. Radiation therapy other than local therapy for myeloma associated bone
lesions
d. Use of any systemic anti-myeloma drug therapy
16. Subject has received prior treatment with a monoclonal antibody within 5
half-lives of initiating study treatment
17. Subject has used any investigational agents within 28 days or 5 half-lives
(whichever is longer) of initiating study treatment
18. Subject has peripheral neuropathy >= Grade 2
19. Subject has any one of the following:
a. Clinically significant abnormal electrocardiogram (ECG) finding at screening
b. Congestive heart failure (New York Heart Association Class III or IV)
c. Myocardial infarction within 12 months prior to starting study treat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective of the study is to determine the recommended dose and<br /><br>regimen of durvalumab either as monotherapy or in combination with POM +/- dex<br /><br>in subjects with RRMM.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are to:<br /><br>* Evaluate the safety and preliminary efficacy of durvalumab monotherapy and in<br /><br>combination with POM +/- dex in subjects with RRMM<br /><br>* Evaluate the PK of durvalumab and POM with or without dex in subjects with<br /><br>RRMM<br /><br><br /><br>The exploratory objectives are to:<br /><br>* Determine the immunogenicity of durvalumab as monotherapy and when given in<br /><br>combination with POM +/- dex in subjects with RRMM<br /><br>* Establish PK/Pd relationship, explore Pd, mechanistic, and predictive<br /><br>biomarkers of durvalumab and POM as single agents and when given in<br /><br>combination in subjects with RRMM<br /><br>* Evaluate minimal residual disease (MRD) and its correlation to clinical<br /><br>outcome measures<br /><br>* Evaluate additional measures of efficacy of durvalumab monotherapy and in<br /><br>combination with POM +/- dex in subjects with RRMM</p><br>