Frailty Score-Guided Dosing of Lenalidomide, Dexamethasone, and Daratumumab for the Treatment of Multiple Myeloma, MMY2035 Study
- Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information. * NOTE: HIPAA authorization may be included in the informed consent or obtained separately
- Newly diagnosed, symptomatic multiple myeloma (MM) who have frailty score of 1 or higher; patients age >= 75 or younger patients with comorbidities (< 75): * Frailty score takes into account age, as well as the geriatric assessments incorporating 3 tools: the Katz Activity of Daily Living (ADL), the Lawton Instrumental Activity of Daily Living (IADL), and the Charlson Comorbidity Index (CCI)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days prior to registration
- Measurable disease according to the International Myeloma Working Group criteria: * Serum M-protein >= 1 g/dL * Urine M-protein >= 200 mg/24 hour (h), or * Serum free light-chain (FLC) assay: involved FLC level >= 10 mg/dL provided serum FLC ratio is abnormal * Clonal bone marrow plasma cells >= 10%
- No prior systemic therapy for myeloma is allowed. Surgery such as vertebroplasty or intramedullary rod placements, and local palliative radiation are allowed as long as subjects have no residual adverse effects (AEs) from prior therapies at the time of screening
- Life expectancy of > 3 months as determined by the treating physician
- Absolute neutrophil count (ANC) >= 1.0 K/mm^3 (obtained within 14 days prior to registration)
- Platelet >= 50 K/mm^3 (obtained within 14 days prior to registration)
- Hemoglobin (Hgb) >= 8 g/dL (obtained within 14 days prior to registration)
- Calculated creatinine clearance >= 30 mL/min using 24 hour urine creatinine clearance (obtained within 14 days prior to registration)
- Bilirubin =< 2 x upper limit of normal (ULN) (obtained within 14 days prior to registration)
- Aspartate aminotransferase (AST) =< 2 x ULN (obtained within 14 days prior to registration)
- Alanine aminotransferase (ALT) =< 2 x ULN (obtained within 14 days prior to registration)
- International normalized ratio (INR) or prothrombin time (PT) =< 2 x ULN (obtained within 14 days prior to registration)
- Activated partial thromboplastin time (aPTT) =< 2 x ULN (obtained within 14 days prior to registration)
- Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 30 days after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method
- As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
- Active infection requiring systemic therapy
- Poorly controlled reactive airway diseases including COPD or asthma. In subjects with underlying disease of chronic obstructive pulmonary disease (COPD) or asthma, spirometric analysis is recommended. Subjects with forced expiratory volume in one second (FEV1) < 50% is excluded
- Other medical conditions interfering with the administration of and compliance to treatments
- Plasma cell leukemia or amyloidosis
- Pregnant or breastfeeding
- Known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years
- Active central nervous system (CNS) involvement by MM
- Contraindication to receive antiplatelet or anticoagulant prophylaxis
- Subject is: * Seropositive for human immunodeficiency virus (HIV) * Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR * Seropositive for hepatitis C (except in the setting of a sustained virologic response [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
I. Evaluate response rate.
II. Evaluate side effects.
I. Evaluate time on therapy.
II. Evaluate progression free survival.
III. Evaluate time to the next line of therapy.
IV. Assess quality of life.
I. Novel biomarkers of cancer cachexia and myeloma bone disease.
OUTLINE: Patients are assigned to 1 of 2 groups.
GROUP I: Patients with frailty score of 1 receive higher dose lenalidomide orally (PO) on days 1-21 and dexamethasone intravenously (IV) or PO on days 1, 8, 15, and 22 . Patients also receive daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
GROUP II: Patients with frailty score of 2 or above receive lower dose lenalidomide PO on days 1-21, and dexamethasone IV or PO on days 1, 8, 15, and 22. Patients also receive daratumumab IV on days 1, 8, 15, and 22 of cycles 1-2, days 1 and 15 of cycles 3-6 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 3 months for 2 years.
Trial Phase Phase II
Trial Type Treatment
Indiana University / Melvin and Bren Simon Cancer Center
- Primary ID CTO-IUSCC-0719
- Secondary IDs NCI-2019-07897
- Clinicaltrials.gov ID NCT04223661