Citarinostat and PVX-410 with or without Lenalidomide in Treating Patients with Smoldering Multiple Myeloma
- Patient has confirmed SMM according to a definition derived from the International Myeloma Working Group (IMWG) definition (International Working Group, 2003): serum M-protein >= 3 g/dL or bone marrow plasma cells (BMPC) > 10%, or both, along with normal organ and marrow function (CRAB) within 4 weeks before baseline * C: absence of hypercalcemia, evidenced by a calcium < 10.5 mg/dL * R: absence of renal failure, evidenced by a creatinine < 1.5 mg/dL (177 umol/L) or calculated creatinine clearance (using the Modification of Diet in Renal Disease [MDRD] formula) > 50 mL/min * A: absence of anemia, evidenced by a hemoglobin > 10 g/dL * B: absence of lytic bone lesions on standard skeletal survey
- Patient is at higher than average risk of progression to active MM, defined as having 2 or more of the following features: * Serum M-protein >= 3 g/dL * BMPC > 10% and < 60% * Abnormal serum free light chains (FLC) ratio (0.26-1.65)
- Patient has a life expectancy of greater than 6 months
- Patient is HLA-A2+
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Platelet count >= 75 x 10^9/L within 2 weeks before baseline
- Absolute neutrophil count (ANC) >= 1.0 x 10^9/L within 2 weeks before baseline
- Bilirubin =< 2.0 mg/dL within 2 weeks before baseline
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (ULN) within 2 weeks before baseline
- If of child-bearing potential, patient agrees to use adequate birth control measures during study participation
- If a female of child-bearing potential, patient has negative serum pregnancy test results within 2 weeks before baseline and is not lactating * Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 24 months with no menses without an alternative medical cause)
- If assigned to receive lenalidomide and a female of reproductive potential, must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS) program
- If assigned to receive lenalidomide, patient must be registered into the mandatory Revlimid REMS program and be willing and able to comply with the requirements of the REMS program
- Patient (or his or her legally accepted representative) has provided written informed consent to participate in the study
- Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up
- Patient has symptomatic MM, as defined by any of the following: * Lytic lesions or pathologic fractures * Anemia (hemoglobin < 10 g/dL) * Hypercalcemia (corrected serum calcium > 11.5 mg/dL) * Renal insufficiency (creatinine > 1.5 mg/dL) * Other: symptomatic hyperviscosity, amyloidosis
- Patient has a history of a prior malignancy within the past 3 years (excluding resected basal cell carcinoma of the skin or in situ cervical cancer)
- Patient has abnormal cardiac status, evidenced by any of the following: * New York Heart Association (NYHA) stage III or IV congestive heart failure (CHF) * Myocardial infarction within the previous 6 months * Symptomatic cardiac arrhythmia requiring treatment or persisting despite treatment
- Patient is receiving any other investigational agent
- Patient has a current active infectious disease or known positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), or hepatitis A virus (HAV)
- Patient has been vaccinated with live attenuated vaccines within 4 weeks before study vaccination
- Any previous treatment with a HDAC inhibitor, including citarinostat
- Had involvement in the planning and/or conduct of the study by association with the sponsor, study drug supplier(s) or study center or was previously enrolled in the present study
- Current or prior use of immunosuppressive medication within 28 days before the first dose of treatment, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Mean QT interval corrected for heart rate (QTc) >= 470 ms calculated from 3 electrocardiograms (ECGs) using Fridericia’s Correction
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, active peptic ulcer disease or gastritis, active bleeding diatheses, or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
I. Determine the safety and tolerability of the PVX-410 tumor vaccine regimen in combination citarinostat (CC-96241) with and without lenalidomide in patients with smoldering multiple myeloma (SMM).
I. Assess immune responses of lymphocytes to HLA A2+ multiple myeloma (MM) cells from patients with SMM and CD8+ cytotoxic T lymphocytes (CTLs) specific to PVX-410.
II. Measure the change in monoclonal (M) serum protein or free light chain (FLC) and urinary FLC levels, as appropriate.
III. Correlate immune response with clinical anti-tumor responses.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I (DOUBLE COMBINATION): Patients receive XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410 subcutaneously (SC) at weeks 0, 2, 4, 6, 8, and 10, and at months 1, 2, 3, 6, and 9 follow up visits. Patients also receive citarinostat orally (PO) once daily (QD) on days 1-21. Treatment with citarinostat repeats every 28 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
ARM II (TRIPLE COMBINATION): Patients receive XBP1-US/XBP1-SP/CD138/CS1 multipeptide vaccine PVX-410 and citarinostat as in Arm I. Patients also receive lenalidomide PO daily on days 1-21. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 1, 2, 3, 6, 9, and 12 months.
Trial Phase Phase I
Trial Type Treatment
Dana-Farber Harvard Cancer Center
Noopur S. Raje
- Primary ID 16-237
- Secondary IDs NCI-2016-01767
- Clinicaltrials.gov ID NCT02886065