Clinical Trials /

Short Course Daratumumab in Patients With Multiple Myeloma

NCT03490344

Description:

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).

Related Conditions:
  • Multiple Myeloma
  • Plasmacytoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Short Course Daratumumab in Patients With Multiple Myeloma
  • Official Title: Short Course Daratumumab in Minimal Residual Disease (MRD) Positive Myeloma Patients After Induction Therapy With/Without Consolidative High Dose Chemotherapy/Autologous Stem Cell Support

Clinical Trial IDs

  • ORG STUDY ID: 18-048
  • NCT ID: NCT03490344

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
DaratumumabParticipants with Multiple Myeloma
LenalidomideParticipants with Multiple Myeloma

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Participants with Multiple MyelomaExperimentalParticipants 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.
  • Daratumumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Multiple Myeloma according to the International Myeloma Working Group definition (2)
             i.e.:Clonal bone marrow plasma cells ≥ 10% or biopsy-proven bony or extramedullary
             plasmacytoma and any one or more of the following myeloma defining events and/or one
             or more of the biomarkers for malignancy at the time of diagnosis:

               -  Myeloma defining events:

               -  Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit
                  of normal or >2.75 mmol/L (>11 mg/dL)

               -  Renal insufficiency: creatinine clearance <40 mL per min or serum creatinine >177
                  µmol/L (>2 mg/dL)

               -  Anemia: hemoglobin value of >20 g/L below the lower limit of normal, or a
                  hemoglobin value <100 g/L

               -  Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or
                  PET-CT

               -  Biomarkers of malignancy:

               -  Clonal bone marrow plasma cell percentage ≥60%

               -  Involved: uninvolved serum free light chain ratio≥100

               -  >1 focal lesions on MRI studies

          -  A very good partial response (VGPR) or better after induction therapy with/without
             consolidative chemotherapy and/or HDT/ASCT.

               -  Very good partial response (VGPR):

               -  Serum and urine M-component detectable by immunofixation but not on
                  electrophoresis or

               -  ≥90% or greater reduction in serum M-component plus urine M-component <100 mg per
                  24 h

               -  Complete response (CR):

               -  Negative immunofixation of serum and urine and

               -  Disappearance of any soft tissue plasmacytomas and

               -  <5% plasma cells in bone marrow

               -  Stringent complete response (sCR)

               -  CR as defined above plus

               -  Normal free light chain ratio and

               -  Absence of clonal cells in bone marrow by immunohistochemistry or
                  immunofluorescence

               -  MRD positive 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of MRD negativity by the completion of 6 months of daratumumab therapy
Time Frame:6 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • bony plasmacytoma
  • extramedullary plasmacytoma
  • Daratumumab
  • lenalidomide
  • Memorial Sloan Kettering Cancer Center
  • 18-048

Last Updated

December 5, 2019