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Daratumumab and Dexamethasone with or without Lenalidomide or Bortezomib for the Treatment of Newly Diagnosed Multiple Myeloma in Older Adults

Trial Status: Active

This phase II trial studies how well daratumumab and dexamethasone with or without lenalidomide or bortezomib works in treating older adults with newly diagnosed multiple myeloma. Immunotherapy with monoclonal antibodies, such as daratumumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as dexamethasone, lenalidomide, bortezomib, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving daratumumab and dexamethasone with lenalidomide or bortezomib may work better in treating older adults with multiple myeloma compared to daratumumab and dexamethasone.

Inclusion Criteria

  • Understand and voluntarily sign an informed consent form
  • Presence of coexisting conditions which in the opinion of the treating physician are likely to result in the development of unacceptable side effects associated with high-dose chemotherapy with stem-cell transplantation
  • Able to adhere to the study visit schedule and other protocol requirements
  • Diagnosed with multiple myeloma and be considered to have active disease with either CRAB criteria (hypercalcemia, renal failure, anemia, or bone lesions) or myeloma defining events (bone marrow >= 60% plasma cells, serum free light chain [sFLC] ratio >= 100 or magnetic resonance imaging [MRI] or positron emission tomography [PET] defined lesions). Patients must not have received an active chemotherapy regimen. Patients may have received palliative radiotherapy at least 2 weeks prior to the study start. Dexamethasone up to 160 mg total dose is allowed prior to participation
  • Measurable myeloma paraprotein levels in serum (>= 0.5 g/dL), urine (>= 0.2 g excreted in a 24-hour urine collection sample) or by serum free light chains (involved free light chain greater than 100 mg/L)
  • Eastern Cooperative Group (ECOG) performance status of 0-2
  • Serum bilirubin levels =< 1.5 times the upper limit of the normal range for the laboratory (ULN)
  • Serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) levels =< 2 x ULN
  • Absolute neutrophil count >= 1,000 cells/mm^3 (1.0 x 10^9/L)
  • Platelets >= 75,000/mm^3
  • Hemoglobin > 8 g/dL (transfusions are allowed)
  • Calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula
  • Men must agree to use a latex condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy

Exclusion Criteria

  • Ongoing severe infection requiring intravenous antibiotic treatment
  • Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 2 years
  • Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia
  • Patients with known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% of predicted normal and, moderate or severe persistent asthma within the past 2 years or uncontrolled asthma. Patients with a history of COPD will have pulmonary function testing to include FEV1
  • Uncontrolled medical problems such as diabetes mellitus, congestive heart failure, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Pregnant or lactating females
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
  • Concurrent use of other anti-cancer agents or treatments
  • Known allergy or hypersensitivity or intolerance to any of the study drugs, hyaluronidase, monoclonal antibodies (mAbs), human proteins, or their excipients (refer to daratumumab investigational brochure [IB]), or known sensitivity to mammalian-derived products
  • 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 a viremia at least 12 weeks after completion of antiviral therapy)


Moffitt Cancer Center
Status: ACTIVE
Contact: Rachid C. Baz
Phone: 813-745-8212


I. To evaluate the efficacy of a daratumumab based response adapted approach.


I. To evaluate the safety profile of daratumumab based therapy in older adults with newly diagnosed myeloma.

II. To identify potential biomarkers for the prediction of response to therapy in multiple myeloma (MM).


I. To study changes in immune profiling with daratumumab therapy.

II. To attempt to validate Ex Vivo Mathematical Myeloma Advisor (EMMA) in silico prediction and dynamics of response.

III. To evaluate a frailty index as a tool for older adults with myeloma treated with novel agents.

OUTLINE: Patients are assigned to 1 of 3 arms.

ARM A: Patients receive daratumumab subcutaneously (SC) over 3-5 minutes 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 and dexamethasone orally (PO) on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with less than a partial response during the first 2 months of treatment are assigned to Arm B or Arm C.

ARM B: Patients receive daratumumab and dexamethasone as in Arm A. Patients also receive lenalidomide PO on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM C: Patients receive daratumumab and dexamethasone as in Arm A. Patients also receive bortezomib SC on days 1, 8, and 15. 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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Moffitt Cancer Center

Principal Investigator
Rachid C. Baz

  • Primary ID MCC-20130
  • Secondary IDs NCI-2019-07700
  • ID NCT04151667