STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA

Sponsor
University of Turin, Italy
Study ID
NCT03829371
Phase
PHASE4
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
65 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Velcade — DRUG
    Subcutaneous use
  • Melphalan — DRUG
    Oral use
  • Prednisone — DRUG
    Oral use
  • Lenalidomide — DRUG
    Oral use
  • Dexamethasone — DRUG
    Oral use
  • Daratumumab — DRUG
    Subcutaneous Injection

Study Details

Multiple myeloma (MM) is a neoplastic disease deriving from an abnormal proliferation of monoclonal plasma cells in the bone marrow. The survival of MM patients varies from less than 6 months to more than 10 years depending on the stage of disease at diagnosis and prognostic factors. Before 2021, in Italy three current standard treatments were approved for elderly or younger patients with significant comorbidities not eligible for autologous stem cell transplantation (ASCT): bortezomib-melphalan-prednisone (VMP), melphalan-prednisone-thalidomide (MPT) and lenalidomide with low-dose dexamethasone (Rd). Daratumumab is a human IgGk monoclonal antibody that targets CD38, that showed clinical benefit in combination with standard-of-care therapy. The addition of Daratumumab (Dara) to VMP and Rd has created two new standards-of-care regimens Dara-VMP and Dara-Rd, which were approved by the EMA in October 2019, and by the AIFA at the beginning of 2021, based on the results of two large phase 3 studies. A consistent fraction of elderly patients with cancer and co-morbidities are at increased risk of developing frailty (an emergent geriatric syndrome), as well as physical and cognitive decline, with negative effect on dependance, nutrition and lifestyle, and eventually on responsiveness to and efficacy of treatments. A frailty scale was recently described that categorized patients with MM as fit, intermediate or frail based on age, comorbidities, and physical and cognitive functioning. The frailty score was a predictor of death, progression of the disease, toxicity and drug discontinuation. The aim of this study was to compare the first line standard treatments, the triplet VMP versus the doublet Rd, that were available when the study was designed. Until 17th December 2021, 228 patients were enrolled in this trial and randomized to VMP vs Rd. Since Dara-VMP and Dara-Rd have recently become the new standard regimens, in this amendment of the study, daratumumab is added to VMP and Rd. In this project, we will compare available first line standard treatments, the triplet VMP versus the doublet Rd with or without daratumumab (Dara-VMP, Dara-Rd), in an unselected population of patients ≥ 65 years affected by MM in every day clinical practice. In the last decade, many novel and expensive drugs have been approved for this disease, yet the general older population is not adequately represented in validating trials. Nevertheless, the results and treatments derived from those registrational trials have often been applied to the real-life older population, with a high risk to produce a negative impact on patient functional capacity and ability to carry out daily tasks, cognitive function, mental status, nutritional condition, social situation/capability to stay at home and finally affecting their quality of life (QoL) and OS. The main aim of the project is to evaluate the best initial treatment for elderly MM patients and to compare benefits, risks, QoL and costs of currently available, standard treatments according to the patient frailty profile.

Key Dates

Start date
Jan 3, 2019
Status verified
Nov 2025
Primary completion
Jan 3, 2027
Completion
Jan 3, 2030

Study Design

Enrollment
450 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: ARM A (enrollment closed)
    Velcade (V): * 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4; * 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 from cycle 5. Melphalan (M): \- 9 mg/m2 orally on days 1, 2 3 and 4 of each cycle. Prednisone (P): \- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is a 42-day cycle. Duration: Maximum 9 cycles can be performed.
  • Experimental: ARM B (enrollment closed)
    Lenalidomide (R): -25 mg orally on days 1-21 of each cycle. Dexamethasone (d): -40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle. Duration: until PD or intolerance.
  • Experimental: ARM A2
    Velcade (V): \- 1.3 mg/m2 subcutaneously twice weekly on weeks 1, 2, 4, and 5 of cycle 1 (days 1,4,8,11,22,25,29,32) and once weekly on weeks 1, 2, 4, and 5 of cycles 2 through 9 (days 1,8,22,29). Melphalan (M): \- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Prednisone (P): \- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Daratumumab: -16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) with oral or intravenous dexamethasone (to manage infusion reactions) at a dose of 20 mg once weekly in cycle 1 (days 1,8,15,22,29,36), every 3 weeks in cycles 2 through 9 (days 1,22), and every 4 weeks thereafter until disease progression or unacceptable toxic effects. Dexamethasone at a dose of 20 mg was substituted for prednisone on day 1 of each cycle.
  • Experimental: ARM B2
    Lenalidomide (R): \- 25 mg orally on days 1-21 of each cycle. Dexamethasone (d): \- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Daratumumab: -intravenous at a dose of 16 mg per kilogram of body weight or 1800 mg Daratumumab subcutaneous (SC) (according to local clinical practice) once weekly during cycles 1 and 2, every 2 weeks during cycles 3 through 6, and every 4 weeks thereafter; preinfusion medications were administered approximately 1 hour before each daratumumab dose.

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: 5 years ]

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