Combination Study for High Risk Multiple Myeloma Patients

Stopped early · Phase 2

Conditions studied: Multiple Myeloma

In brief

Despite the recent introduction of novel anti-multiple myeloma (MM) agents, high risk MM remains with poor prognosis and a therapeutic challenge. Elotuzumab (ELO) is a humanized monoclonal antibody that recognizes CS1/CD139, a molecule highly expressed in MM cells. The ELO (10 mg/kg), lenalidomide (LEN) and dexamethasone (DEX) combination achieves high overall response rates (ORR) and long progression-free survival (PFS) for patients with relapsed/refractory disease (RR) MM and those with impaired renal function. However, its efficacy for MM patients with high risk characteristics is still unknown. Pomalidomide (POM) is a recently approved immunomodulatory agent (IMiD) that produces response rates for high-risk RRMM patients when used in combination with DEX and other agents, including the proteasome inhibitor (PI) bortezomib (BTZ). POM has also demonstrated activity for LEN refractory patients. Carfilzomib (CFZ) is a potent second generation PI that has shown to be efficacious for IMiD and BTZ refractory patients as well as high risk patients carrying cytogenetic abnormalities. In this study, we propose to evaluate efficacy and safety of ELO in combination with POM, DEX and CFZ for high-risk RRMM patients.

Key facts

Study ID: NCT03104270
Run by: Oncotherapeutics
People needed: 13
Starts: 2017-03-13
Expected to finish: 2020-01-23
Last updated by the study team: 2022-03-31

Who can join

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

You may qualify if…

Subjects must be adults (age ≥ 18 years at the time of signing the informed consent document) and must meet all of the following inclusion criteria to be enrolled in the study:
ECOG/Zubrod performance status of 0-2 at study entry
Has a diagnosis of high-risk MM by showing any of the following a-f criteria: :
Presence of conventional cytogenetic markers such as deletion of 17p-p53, translocations involving t(14;16) and t(14;20)
Plasma cell leukemia (PCL) (> 2.0 × 109/L circulating plasma cells by standard differential)
Extramedullary MM
Doubling in levels of a MM markers in the past 3 months such as any of the following criteria alone or in combination: i) Serum M-protein ≥ 1.0 g/dL, or ii) Urine M-protein ≥ 400 mg/24 hours, or iii) Only in patients who do not meet i or ii, then use serum free light chain (SFLC) > 200 mg/L (involved light chain) and an abnormal kappa/lambda ratio
Refractoriness to their most recent lenalidomide-containing regimen and proteasome inhibitor-containing regimen.
Renal failure related to MM with creatinine clearance (CrCl) >15 mL/min but <30 mL/min as calculated by Cockcroft-Gault equation (Appendix 14.8).
Has previously received more than two lines of therapy including a lenalidomide-containing regimen and proteasome inhibitor-containing regimen.
Currently demonstrating progressive disease
Life expectancy greater than 3 months
Laboratory test results within these ranges at Screening and confirmed at enrollment prior to drug dosing on Cycle 1 Day 1:
ANC ≥ 1.5 x 109/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 1.0 x 109/L
Platelet count ≥ 75 x 109/L; if the bone marrow is extensively infiltrated ( ≥ 70% plasma cells) then ≥ 50 x 109/L
Hemoglobin ≥ 8 g/dL
Women of childbearing potential (WOCBP†) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 10-14 days prior to and again within 24 hours of starting study drug regimen
† A WOCBP (women of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 120 days post-treatment completion. Subject must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts taking study drugs. WOCBP must also agree to ongoing pregnancy testing. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Section 10.3.5.2, Appendix 4 and Appendix 5. Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug plus 5 half-lives of the study drug plus 90 days (duration of sperm turnover) for a total of 154 days post-treatment completion. Men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. See Section 10.3.5, Appendix 4 and Appendix 5
Able to take aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg/daily as prophylactic anticoagulation (subjects intolerant to ASA may use warfarin or low molecular weight heparin)
Written informed consent in accordance with federal, local, and institutional guidelines
Able to adhere to the study visit schedule and other protocol requirements

You may not qualify if…

Subjects meeting any of the following exclusion criteria are not to be enrolled in the study:
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 19
Waldenström's macroglobulinemia
Received the following prior therapy:
Elotuzumab
Chemotherapy within 3 weeks of study drugs (6 weeks for nitrosourea, melphalan or monoclonal antibodies)
Corticosteroids (>10 mg/daily prednisone or equivalent) within 3 weeks of study drugs
Immunomodulatory therapy within one week before study drugs
Antibody therapy within 3 weeks before study drugs
Extensive radiation therapy (total maximum radiation doses of 50Gy to any individual site or 30Gy for the disseminated MM of bone) within 3 weeks before study drugs. Receipt of localized radiation therapy does not preclude enrollment.
Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 3 weeks prior to first dose
Use of any other experimental drug or therapy within 3 weeks of study drugs
Received the following transplant therapies:
Less than 12 weeks from auto transplant
Less than 16 weeks from allo transplant
Less than 4 weeks since any plasmapheresis
Major surgery within 4 weeks prior to first dose
Impaired cardiac function or clinically significant cardiac diseases, including any one of the following:
Myocardial infarction within last 6 months prior to enrollment
Active congestive heart failure (New York Heart Association (NYHA) Class III or IV) heart failure
Uncontrolled angina and/or hypertension
Clinically significant pericardial disease
Severe uncontrolled ventricular arrhythmias
Echocardiogram or MUGA evidence of LVEF below institutional normal within 28 days prior to enrollment
Electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

Where it is running

California Cancer Associates for Research & Excellence (cCARE) — Encinitas, California, United States
Robert A. Moss, MD, FACP, Inc — Fountain Valley, California, United States
Pacific Cancer Care — Monterey, California, United States
James Berenson, MD, Inc — West Hollywood, California, United States
Millennium Oncology Research Clinic — Pembroke Pines, Florida, United States
Regional Cancer Care Associates MD LLC — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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