Short Course Daratumumab in Patients With Multiple Myeloma

Phase 2

Completed

Conditions: Multiple Myeloma

Interventions: Drug: Daratumumab
Drug: Lenalidomide

Registration Number: NCT03490344

Lead Sponsor: Memorial Sloan Kettering Cancer Center

Brief Summary: The purpose of this study is to test the safety of short course Daratumumab in combination with lenalidomide and to find out what effects, if any, short course Daratumumab in combination with lenalidomide has on people and their risk of multiple myeloma. The study is also designed to test the amount of remaining myeloma cells in your body after treatment with daratumumab which is known as minimal residual disease (MRD).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Patients with a diagnosis of Multiple Myeloma who have achieved a VGPR or better (based on best response) after induction with or without consolidation therapy/ HDT 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, MDRD, or CKD-EPI formula. If the calculated CrCl based on Cockcroft-Gault method, MDRD, or CKD-EPI is <45 mL/min, patient will have a 24 hr urine collection to measure CrCl.
Age ≥18 years
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, 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, hemoglobin ≥8 g/dL, and 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 ULN, and AST and ALT < 2.5 x ULN

Exclusion Criteria

Patients with a diagnosis of 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 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) 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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants with Multiple Myeloma	Lenalidomide	Participants with MM with very good partial response (VGPR) or better after induction therapy with/without consolidative HDT/ASCT and MRD positive by bone marrow flow cytometry and MM participants who were previously MRD negative after induction and consolidation and recently (within last 3 months) turned MRD positive by bone marrow flow cytometry will be enrolled.
Participants with Multiple Myeloma	Daratumumab	Participants with MM with very good partial response (VGPR) or better after induction therapy with/without consolidative HDT/ASCT and MRD positive by bone marrow flow cytometry and MM participants who were previously MRD negative after induction and consolidation and recently (within last 3 months) turned MRD positive by bone marrow flow cytometry will be enrolled.

Primary Outcome Measures

Name	Time	Method
Number of Participants With MRD Negativity by the Completion of 6 Months of Daratumumab Therapy	6 months

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (7): Memorial Sloan Kettering Nassau
🇺🇸
Uniondale, New York, United States
Memoral Sloan Kettering Monmouth
🇺🇸
Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen
🇺🇸
Montvale, New Jersey, United States
Memorial Sloan Kettering Commack
🇺🇸
Commack, New York, United States
Memoral Sloan Kettering Westchester
🇺🇸
Harrison, New York, United States
Memoral Sloan Kettering Basking Ridge
🇺🇸
Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Cancer Center
🇺🇸
New York, New York, United States