Multiple myeloma (MM) with 2 to 4 prior therapies including daratumumab (DARA), an immunomodulatory (IMiD) compound and a proteasome inhibitor (PI) and demonstrated disease progression on or within 60 days of completion of the last therapy.
Conditions
Interventions
Months 3 to 6 on Days 1 and 15 of a 28-day month
and Months >= 7 on Day 1 of a 28-day month [DARA + BTZ + dexamethasone (DVd)] Intravenous DARA administered at a starting dose of 16 mg/kg for: Months 1 to 3 on Days 1, 8 and 15 of a 21-day month
Months 4 to 8 on Day 1 of a 21-day month
and Months >= 9 on Day 1 of a 28-day month [IXA + LEN + dexamethasone (IRd)] Dexamethasone will be dosed at 40 mg/day on Days 1, 8, 15 and 22 of a 28-day month
Generic name etc: pomalidomide
INN of in
Sponsors
Bristol-Myers Squibb K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must satisfy the following criteria to be enrolled in the study: 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 within this protocol and for a subject randomized to Treatment Arm A, subject agrees to continued follow-up for up to 15 years as mandated by the regulatory guidelines for gene therapy trials. 4. Subject has documented diagnosis of MM and 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 urine: Serum immunoglobulin free light chain >= 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio 5. Subject has received at least 2 but no greater than 4 prior MM regimens. 6. Subject has received prior treatment with DARA, a proteasome inhibitor and an immunomodulatory compound-containing regimen for at least 2 consecutive cycles. 7. Subject must be refractory to the last treatment regimen. Refractory is defined as documented progressive disease during or within 60 days (measured from the last dose of any drug within the regimen) of completing treatment with the last anti-myeloma regimen before study entry. 8. Subject achieved a response (minimal response [MR] or better) to at least 1 prior treatment regimen. 9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 10. Recovery to Grade 1 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 2 peripheral neuropathy. 11. Adequate vascular access for leukapheresis 12. Females of childbearing potential (FCBP)1 must: a. Have negative pregnancy test(s) as verified by the Investigator. This applies even if the subject practices true abstinence from heterosexual contact. 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 measures of contraception without interruption. c. Agree to abstain from breastfeeding during study participation. d. Refrain from tissue donation including egg cell donation or any other tissue/blood/organ donations. 13. Male subjects must: a. Practice true abstinence 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, even if he has undergone a successful vasectomy. b. Tissue donation including sperm or any other tissue/blood/organ donations. 14. Only subjects that would be considered for any of the 5 proposed standard regimens (DPd, DVd, IRd, Kd or EPd), as judged by the Investigator, should be included in the study.
Exclusion criteria
Exclusion criteria: The presence of any of the following will exclude a subject from enrollment: 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 nonsecretory MM. 5. Subject has any of the following laboratory abnormalities: a. Absolute neutrophil count (ANC) = 50% of bone marrow nucleated cells are plasma cells (it is not permissible to transfuse a subject to reach this level) c. Hemoglobin 13.5 mg/dL (> 3.4 mmol/L) f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limit of normal (ULN) g. Serum total bilirubin > 1.5 x ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome h. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) > 1.5 x ULN, or history of Grade >= 2 hemorrhage within 30 days, or subject requires ongoing treatment with chronic, therapeutic dosing of anticoagulants (eg, warfarin, low molecular weight heparin, Factor Xa inhibitors) 6. Subject has inadequate pulmonary function defined as oxygen saturation (SaO2) = 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 tumor, nodes, metastasis [TNM] clinical staging system) or prostate cancer that can be treated with curative intent 8. Subject has active or history of plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. 9. Subject with known central nervous system (CNS) involvement with myeloma. 10. Subject has clinical evidence of pulmonary leukostasis and disseminated intravascular coagulation. 11. Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) 50% of predicted normal. 12. Subject has a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or other CNS bleed, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis. 13. Subject was treated with DARA in combination with POM with or without dexamethasone as part of their most recent anti-myeloma treatment regimen, cannot receive DPd as bridging therapy but may receive DVd, IRd, Kd or EPd as bridging as per Investigator's discretion if randomized to Treatment Arm A. 14. Subject was treated with DP +/- d as part of their most recent anti-myeloma treatment regimen, cannot
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy - Progression-free Survival (PFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety Efficacy Other - Overall Survival (OS) - Event-free Survival (EFS) - Overall Response Rate (ORR) - Minimal Residual Disease (MRD) - Complete Response (CR) Rate etc. | — |
Countries
Europe, Japan, North America
Contacts
Public ContactJin Hayakawa
Bristol-Myers Squibb
Outcome results
None listed