Daratumumab and Lenalidomide in Treating Patients with Minimal Residual Disease Positive Multiple Myeloma after Induction Therapy with or without High-Dose Chemotherapy with Stem Cell Support
- Patients with a diagnosis of multiple myeloma who have achieved a very good partial response (VGPR) or better (based on best response) after induction with or without consolidation therapy/high-dose therapy (HDT) autologous stem cell transplantation (ASCT)
- MRD positive at screening by flow cytometry
- Additionally, patients who were previously MRD negative after induction therapy with/without consolidative HDT/ASCT and have turned MRD positive (by flow cytometry) based on bone marrow done at screening and do not have any evidence of progressive disease are eligible
- Patients must be on standard of care lenalidomide maintenance therapy for at least 6 months at the time of study enrollment.
- Patient can be receiving bisphosphonate therapy per the treating oncologist's discretion.
- Creatinine clearance >= 45 ml/min using the Cockcroft-Gault method, Modification of Diet in Renal Disease (MDRD), or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. If the calculated creatinine clearance (CrCl) based on Cockcroft-Gault method, MDRD, or CKD-EPI is < 45 mL/min, patient will have a 24 hour (hr) urine collection to measure CrCl.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Male or female patient who accepts and is able to use recognized effective contraception (oral contraceptives, intrauterine contraceptive device [IUCD], barrier method of contraception in conjunction with spermicidal jelly) throughout the study when relevant.
- Absolute neutrophil count (ANC) >= 1.0 x 10^9 /L. No transfusion or growth factor support for one week prior to labs.
- Hemoglobin >= 8 g/dL. No transfusion or growth factor support for one week prior to labs.
- Platelet count >= 75 x 10^9/L. No transfusion or growth factor support for one week prior to labs.
- Adequate hepatic function, with bilirubin < 1.5 x the upper limit of normal (ULN)
- Adequate hepatic function, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN
- Patients with a diagnosis of multiple myeloma (MM) not achieving a VGPR or better to the most recent therapy
- Patients with a diagnosis of MM who are MRD negative by flow cytometry
- Patients must not have measurable disease at the time of enrollment. Measurable disease is defined as follows- * Serum monoclonal protein > 0.5 gm/dL * Urine monoclonal protein > 200 mg/24 hours * Involved serum free light chain > 10 mg/dL
- Pregnant or lactating females.
- Uncontrolled hypertension or diabetes.
- Has significant cardiovascular disease with New York Heart Association (NYHA) class III or IV symptoms, or hypertrophic cardiomegaly, or restrictive cardiomegaly, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia.
- Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance of study requirements.
- Active infection requiring treatment within two weeks prior to first dose.
- Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy.
- Major surgery within 1 month prior to enrollment.
- Previous therapy with daratumumab or other anti-CD38 monoclonal antibodies.
- History of other malignancy (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma) except if the patient has been free of symptoms and without active therapy during at least 5 years.
- Active hepatitis B or C infection.
- 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 [anti-HBs]) 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. To determine the rate of minimal residual disease (MRD) negativity by the completion of 6 months of daratumumab therapy.
I. To assess the rate of sustained MRD negativity in the bone marrow.
II. To determine duration of MRD negativity.
III. To compare MRD techniques of multi-parametric flow cytometry with next-generation
sequencing and mass spectrometry.
IV. To determine progression-free and overall survival.
I. The gene panel MyType (or comparable next generation sequencing panel) will explore whether any mutations appear to be associated with response to therapy or toxicity associated with therapy.
II. MyType will (or comparable next generation sequencing panel) also be evaluated using samples at the time of progression of disease and will be compared to the pre-treatment baseline samples to explore whether pathways leading to emergence of resistance to the drug regimen can be identified.
Patients receive daratumumab intravenously (IV) on days 1, 8, 15, and 22 of cycles 1-2, then on days 1 and 15 of cycles 3-6. Patients also receive lenalidomide orally (PO) daily on days 1-28. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. After 6 cycles, patients may continue lenalidomide maintenance as standard of care treatment.
After completion of study treatment, patients are followed up at 1 month, 1 year, and 3 years.
Trial Phase Phase II
Trial Type Treatment
Memorial Sloan Kettering Cancer Center
- Primary ID 18-048
- Secondary IDs NCI-2018-00871
- Clinicaltrials.gov ID NCT03490344