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Short Course Daratumumab in Patients With Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03490344
Recruitment Status : Recruiting
First Posted : April 6, 2018
Last Update Posted : December 9, 2019
Sponsor:
Collaborator:
Janssen Scientific Affairs, LLC
Information provided by (Responsible Party):
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).

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: Lenalidomide Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 3, 2018
Estimated Primary Completion Date : October 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: Participants with Multiple Myeloma
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.
Drug: Daratumumab
  • Cycles 1 and 2: Daratumumab 16mg/kg weekly per cycle (28 days) as intravenous infusion (total duration: 8 weeks)
  • Cycles 3-6: Daratumumab 16mg/kg once every 2 weeks per cycle (28 days) as intravenous infusion (total duration: 16 weeks)

Drug: Lenalidomide
Lenalidomide maintenance therapy to be administered as standard treatment to all participants. This is administered as 5-15 mg daily 21-28/28 day cycle.




Primary Outcome Measures :
  1. Rate of MRD negativity by the completion of 6 months of daratumumab therapy [ Time Frame: 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03490344


Contacts
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Contact: Sham Mailankody, MBBS 212-639-2131 mailanks@mskcc.org
Contact: C. Ola Landgren, MD, PhD 212-639-5126 landgrec@mskcc.org

Locations
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United States, New Jersey
Memoral Sloan Kettering Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Sham Mailankody, MBBS    212-639-2131      
Memoral Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Sham Mailankody, MBBS    212-639-2131      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Sham Mailankody, MBBS    212-639-2131      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Sham Mailankody, MBBS    212-639-2131      
Memoral Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Sham Mailankody, MBBS    212-639-2131      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Sham Mailankody, MBBS    212-639-2131      
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Sham Mailankody, MBBS    212-639-2131      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Janssen Scientific Affairs, LLC
Investigators
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Principal Investigator: Sham Mailankody, MBBS Memorial Sloan Kettering Cancer Center

Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03490344     History of Changes
Other Study ID Numbers: 18-048
First Posted: April 6, 2018    Key Record Dates
Last Update Posted: December 9, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
bony plasmacytoma
extramedullary plasmacytoma
Daratumumab
lenalidomide
Memorial Sloan Kettering Cancer Center
18-048
Additional relevant MeSH terms:
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Multiple Myeloma
Daratumumab
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents