Less Doses of Daratumumab Are Adequate to Achieve Response in Newly Diagnosed Multiple Myeloma

Condition(s) studied

Investigational drug(s) / intervention(s)

Daratumumab (Intravenously): Daratumumab will be administered intravenously at 16 mg/kg according to the protocol-specified schedule (Days 1, 15, 29, 50, 71, and 92), during the four-cycle induction period.

Bortezomib (BTZ): Bortezomib will be administered at 1.3 mg/m² weekly, by the subcutaneous or intravenous route, as specified in the study protocol.

Len (lenalidomide): Lenalidomide will be administered orally at a dose of 15-25 mg once daily for 21 days of each 28-day cycle, as specified in the study protocol.

Dexamethasone: Dexamethasone will be administered at a dose of 40 mg once weekly, orally or intravenously, as specified in the study protocol.

Study summary

The goal of this clinical trial is to evaluate whether a modified (less frequent) dosing schedule of daratumumab, when added to standard VRd therapy, can be an effective induction regimen for treating newly diagnosed multiple myeloma (NDMM).

The main questions it aims to answer are:

1. Does the modified (less frequent) daratumumab dosing regimen increase the rate of MRD (minimal residual disease) negativity after 4 cycles of induction therapy (as compared to standard VRd therapy)?
2. Is the modified less-frequent dosing schedule safe and does it achieve adequate drug levels
3. What is the clinical response of patients to the treatment?

Treatment regimen Daratumumab (Dara), Bortezomib, Lenalidomide, and Dexamethasone will be given together for four cycles of induction therapy

Duration of each cycle will be 28 days

1. Daratumumab will be given at standard dose of 16mg/kg - Day 1, 15, 29, 50, 71, and 92 (First three doses every 2 weeks, followed by the next three doses every 3 weeks). This will be given intravenously in saline
2. Bortezomib: 1.3 mg/m2 - Given once weekly subcutaneously (similar to insulin)
3. Lenalidomide: 15-25 mg orally for 21 days, followed by a 7-day gap.
4. Dexamethasone: 40mg given once weekly

Response Assessment

* Response assessment - A bone marrow test will be done within two weeks of end of cycle 4 in order to assess the cancer burden via a special test called MRD (minimal residual disease) in the bone marrow.
* Blood tests will be performed to assess your response to treatment (serum protein electrophoresis, immunofixation electrophoresis and serum free light chain assay) after cycle 2 (between day 51-day 56) and cycle 4 (between 107-112). These blood tests are routinely done for all myeloma patients during their treatment to assess response.

Eligibility

Primary outcome measure(s)

• Post-induction MRD negativity rate — At the end of Cycle 4 (each induction cycle is 28 days; MRD assessed within 2 weeks after completion of Cycle 4 [approximately Days 113-127]
  Proportion of participants achieving measurable (minimal) residual disease (MRD) negativity at the end of four cycles of induction therapy with daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd). MRD negativity will be assessed

Trial sites (2)

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