Belantamab Mafodotin, Pomalidomide and Dexamethasone for the Treatment of High-Risk Myeloma
Plasma cell neoplasm
18 Years and older, Male and Female
This phase II trial studies the effect of belantamab mafodotin, pomalidomide, and dexamethasone in treating patents with high-risk myeloma. Belantamab mafodotin is a monoclonal antibody, called belantamab, linked to a chemotherapy drug, called mafodotin. Belantamab is a form of targeted therapy because it attaches to specific molecules on the surface of cancer cells, known as BCMA receptors, and delivers mafodotin to kill them. Chemotherapy drugs, such as pomalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Anti-inflammatory drugs, such as dexamethasone lower the body’s immune response and are used with other drugs in the treatment of some types of cancer. Giving belantamab mafodotin, pomalidomide, and dexamethasone may kill more cancer cells.
I. To evaluate the efficacy of the combination of belantamab mafodotin, pomalidomide and dexamethasone (BPd) by assessing the >= complete response (CR) rates with BPd maintenance in patients with high-risk myeloma by International Myeloma Working Group (IMWG) criteria.
I. To evaluate the safety and tolerability of the combination of BPd in patients with high-risk myeloma.
II. To determine the antitumor activity of BPd maintenance among high-risk myeloma patients.
I. To evaluate the changes in microenvironment among patients receiving BPd maintenance.
Patients receive belantamab mafodotin intravenously (IV) over 30 minutes on day 1 of every other cycle, pomalidomide orally (PO) once daily (QD) on days 1-21, and dexamethasone PO QD on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months.
- Transplant-eligible myeloma patient that has undergone autologous stem cell transplant (ASCT) within one year of their diagnosis and has achieved >= partial response (PR) based on IMWG standard criteria. Patients will be enrolled within day 60-100 after ASCT
- Patient’s with high-risk disease defined as
* Presence of del(17p); t(4;14); t(14;16); t(14;20) by fluorescence in situ hybridization (FISH) or by cytogenetics (CTG)
* Plasma cell leukemia at diagnosis with >= 20% circulating plasma cells on peripheral blood
- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- Participant must be >= 18 years of age
- Absolute neutrophil count (ANC) >=1.5 x 10^9/L (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Hemoglobin >= 8.0 g/dL (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Platelets >= 75 x 10^9/L (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (Isolated bilirubin >= 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%) (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Alanine aminotransferase (ALT) =< 2.5 x ULN (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Estimated glomerular filtration rate (eGFR) >= 30 mL/min/ 1.73 m^2 (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Spot urine (albumin/creatinine ratios) < 500 mg/g (56 mg/mmol) (performed within 28 days of initiation of protocol therapy unless otherwise specified)
- Female participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
* Is not a woman of childbearing potential (WOCBP)
* Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), preferably with low user dependency, during the intervention period and for at least 4 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. A WOCBP must have a negative highly sensitive serum pregnancy test (as required by local regulations) within 72 hours before the first dose of study intervention. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with a nearly undetected pregnancy.
Nonchildbearing potential is defined as follows (by other than medical reasons):
* >= 45 years of age and has not had menses for > 1 year
* Patients who have been amenorrhoeic for < 2 years without history of a hysterectomy and oophorectomy must have a follicle stimulating hormone value in the postmenopausal range upon screening evaluation
* Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure
- Male participants: contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male participants are eligible to participate if they agree to the following during the intervention period and for 6 months after the last dose of study treatment to allow for clearance of any altered sperm:
* Refrain from donating sperm PLUS either:
* Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
* Must agree to use contraception/barrier as detailed below:
** Agree to use a male condom, even if they have undergone a successful vasectomy, and female partner to use an additional highly effective contraceptive method with a failure rate of < 1% per year as when having sexual intercourse with a woman of childbearing potential (including pregnant females)
- All prior treatment-related toxicities (defined by National Cancer Institute- Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.03) must be =< grade 1 at the time of enrolment except for alopecia
- Participant must be able to understand the study procedures and agree to participate in the study by providing written informed consent
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