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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 4
Locations
Italy
Study Type
Interventional
Intervention
Velcade
Melphalan
Prednisone
Lenalidomide
Dexamethasone
Daratumumab
Sponsored by
University of Turin, Italy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring TRANSPLANT INELIGIBLE, STANDARD TREATMENTS

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients has given voluntary written informed consent before the performance of any study related procedure;
  • Patients with newly diagnosed symptomatic multiple myeloma (NDMM) based on standard IMWG (International Myeloma Working Group) criteria:
  • Clonal bone marrow plasma cells >=10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events:

  • evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically

    • Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)
    • Renal insufficiency: creatinine clearance (CLcr)<40 mL per minute (measured or estimated by validated equations) or serum creatinine > 177 micro mol/L (>2mg/dL)
    • Anemia: hemoglobin value of >20g/L below the lower limit of normal, or a hemoglobin value <100g/L
    • Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement

  • Any one or more of the following biomarkers of malignancy:

    • Clonal bone marrow plasma cell percentage >=60% (clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)
    • Involved:uninvolved serum free light chain ratio >=100 (values based on the serum Freelite assay. The involved free light chain must be >=100 mg/L)
    • >1 focal lesion detected by MRI (magnetic resonance imaging) studies (each focal lesion must be 5 mm or more in size
  • According to physician's opinion, patients can undergo either one of the two standard treatments and procedures;
  • Females of childbearing potential (FBCP) must use an effective contraceptive method for 28 days before the study treatment, during the treatment and for at least 3 months after the last dose of study drugs;
  • Male subjects must use an effective barrier method if sexually active with FCBP during treatment and for at least 6 months after the last dose of study drug;
  • Patients should be ineligible for ASCT, defined as:
  • >= 65 years old

  • younger than 65 years but who reject the transplant procedure or with abnormal cardiac, pulmonary, hepatic and renal function defined as [1]:

    • LVEF (left ventricular ejection fraction) < 40%
    • FEV1 (forced expiratory volume-1 second) < 40%
    • Bilirubin > 1.5 UNL, AST/ALT >2.5 UNL Creatinine clearance < 60 mL/min.

Exclusion Criteria:

  • Hypersensitivity to any active substance or to any of the excipients (lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, boron, mannitol, nitrogen, crospovidone, colloidal anhydrous silica, hypromellose, titanium dioxide, macrogol, talc, sodium starch glycolate, sodium benzoate, propylene glycol, sodium dihydrogen phosphate, hydroxypropyl beta cyclodextrin, sodium saccharin, sodium EDTA, sodium hydroxide, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), recombinant human hyaluronidase (rHuPH20));
  • Hereditary intolerance to fructose;
  • Pregnant and lactating women;
  • FBCP that do not follow the Pregnancy Prevention Plan requirements;
  • Acute diffuse infiltrative pulmonary and pericardial disease;
  • Acute viral infections (e.g. herpes simplex or ocular herpes simplex, herpes zoster, varicella);
  • Systemic mycotic or bacterial infections, unless specific anti-infectious therapy is ongoing;
  • Peptic ulcer;
  • Psychosis;
  • Administration of prophylactic vaccine from 8 to 2 weeks before starting treatment.

Sites / Locations

  • Dipartimento di Biotecnologie Molecolari e Scienze per la SaluteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

ARM A (enrollment closed)

ARM B (enrollment closed)

ARM A2

ARM B2

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Progression-free survival (PFS)
Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.

Secondary Outcome Measures

Overall response rate (ORR)
Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.
Duration of response (DOR)
Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.
Overall survival (OS)
Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.
Progression-free survival 2 (PFS2)
Time from randomization to objective tumor progression on next-line treatment or death from any cause.
Time to next therapy (TNT)
Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.
Time to progression (TTP)
Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.
Adverse events
Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0.
Rate of treatment discontinuation or death for toxicity
Incidence of treatment discontinuation for toxicities as well as the rate of death for toxicity will be evaluated during the entire duration of the trial (toxicities evaluated according to NCI-CTCAE v. 4.0)
Frailty score
Validation of Myeloma Frailty Score (fit score=0; intermediate-fitness score=1, and frail score≥2) that assess comorbidities, cognitive and physical status in real population according to geriatric assessment and considering patients' non-Myeloma polydrug therapies.
Quality of Life through Health-Related QoL (HRQoL)
Quality of Life will be evaluated through questionnaire: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire).
Quality of Life through Health-Related QoL (HRQoL)
Quality of Life will be evaluated through questionnaire for MM patients: QLQ-MY20 (a specific 20- item MM module).
Quality of Life through Health-Related QoL (HRQoL)
Quality of Life will be evaluated through questionnaire: EQ-5D-5L (a generic assessment of five health categories and overall health score).
Direct health related costs and indirect costs
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating working activities.
Direct health related costs and indirect costs
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating care assistance.
Direct health related costs and indirect costs
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating health care visit.
Risk of infectious complications
Infectious risk complications will be evaluated through a scale evaluating the number of adverse events, severity, type of infection, need for hospitalization (yes/no), number of days of suspension of study treatment. All these data will be combined in the statistical analysis to combine different outcome of treatments.

Full Information

First Posted
January 22, 2019
Last Updated
June 28, 2023
Sponsor
University of Turin, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT03829371
Brief Title
STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
Official Title
A RANDOMIZED, MULTICENTER, OPEN LABEL STUDY COMPARING TWO STANDARD TREATMENTS, BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) WITH OR WITHOUT DARATUMUMAB (Dara-VMP) VS LENALIDOMIDE-DEXAMETHASONE (Rd) WITH OR WITHOUT DARATUMUMAB (Dara-Rd) IN AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) INELIGIBLE COMMUNITY POPULATION AFFECTED BY MULTIPLE MYELOMA (MM)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2019 (Actual)
Primary Completion Date
January 3, 2024 (Anticipated)
Study Completion Date
January 3, 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Turin, Italy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
All patients will be randomized in a 1:1 ratio to receive: ARM A (enrollment closed): Bortezomib (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 in cycles 5-9. 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 to be repeated every 42 days. Duration: Maximum 9 therapy cycles can be performed. After 9 cycles, patients will be observed until progression disease or the start of a new line of therapy. ARM A2: Bortezomib (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 (Dara) 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. 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 cycles. Duration: patients will receive treatment until any sign of progression or intolerance. 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 (Dara) 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
TRANSPLANT INELIGIBLE, STANDARD TREATMENTS

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
450 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ARM A (enrollment closed)
Arm Type
Experimental
Arm Description
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.
Arm Title
ARM B (enrollment closed)
Arm Type
Experimental
Arm Description
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.
Arm Title
ARM A2
Arm Type
Experimental
Arm Description
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.
Arm Title
ARM B2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Velcade
Intervention Description
Subcutaneous use
Intervention Type
Drug
Intervention Name(s)
Melphalan
Intervention Description
Oral use
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Oral use
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
Oral use
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Oral use
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Intervention Description
Subcutaneous Injection
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.
Time Frame
5 years
Title
Duration of response (DOR)
Description
Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.
Time Frame
5 years
Title
Overall survival (OS)
Description
Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.
Time Frame
5 years
Title
Progression-free survival 2 (PFS2)
Description
Time from randomization to objective tumor progression on next-line treatment or death from any cause.
Time Frame
5 years
Title
Time to next therapy (TNT)
Description
Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.
Time Frame
5 years
Title
Time to progression (TTP)
Description
Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.
Time Frame
5 years
Title
Adverse events
Description
Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0.
Time Frame
5 years
Title
Rate of treatment discontinuation or death for toxicity
Description
Incidence of treatment discontinuation for toxicities as well as the rate of death for toxicity will be evaluated during the entire duration of the trial (toxicities evaluated according to NCI-CTCAE v. 4.0)
Time Frame
5 years
Title
Frailty score
Description
Validation of Myeloma Frailty Score (fit score=0; intermediate-fitness score=1, and frail score≥2) that assess comorbidities, cognitive and physical status in real population according to geriatric assessment and considering patients' non-Myeloma polydrug therapies.
Time Frame
5 years
Title
Quality of Life through Health-Related QoL (HRQoL)
Description
Quality of Life will be evaluated through questionnaire: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire).
Time Frame
5 years
Title
Quality of Life through Health-Related QoL (HRQoL)
Description
Quality of Life will be evaluated through questionnaire for MM patients: QLQ-MY20 (a specific 20- item MM module).
Time Frame
5 years
Title
Quality of Life through Health-Related QoL (HRQoL)
Description
Quality of Life will be evaluated through questionnaire: EQ-5D-5L (a generic assessment of five health categories and overall health score).
Time Frame
5 years
Title
Direct health related costs and indirect costs
Description
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating working activities.
Time Frame
5 years
Title
Direct health related costs and indirect costs
Description
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating care assistance.
Time Frame
5 years
Title
Direct health related costs and indirect costs
Description
Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating health care visit.
Time Frame
5 years
Title
Risk of infectious complications
Description
Infectious risk complications will be evaluated through a scale evaluating the number of adverse events, severity, type of infection, need for hospitalization (yes/no), number of days of suspension of study treatment. All these data will be combined in the statistical analysis to combine different outcome of treatments.
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients has given voluntary written informed consent before the performance of any study related procedure; Patients with newly diagnosed symptomatic multiple myeloma (NDMM) based on standard IMWG (International Myeloma Working Group) criteria: Clonal bone marrow plasma cells >=10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events: evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL) Renal insufficiency: creatinine clearance (CLcr)<40 mL per minute (measured or estimated by validated equations) or serum creatinine > 177 micro mol/L (>2mg/dL) Anemia: hemoglobin value of >20g/L below the lower limit of normal, or a hemoglobin value <100g/L Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement Any one or more of the following biomarkers of malignancy: Clonal bone marrow plasma cell percentage >=60% (clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used) Involved:uninvolved serum free light chain ratio >=100 (values based on the serum Freelite assay. The involved free light chain must be >=100 mg/L) >1 focal lesion detected by MRI (magnetic resonance imaging) studies (each focal lesion must be 5 mm or more in size According to physician's opinion, patients can undergo either one of the two standard treatments and procedures; Females of childbearing potential (FBCP) must use an effective contraceptive method for 28 days before the study treatment, during the treatment and for at least 3 months after the last dose of study drugs; Male subjects must use an effective barrier method if sexually active with FCBP during treatment and for at least 6 months after the last dose of study drug; Patients should be ineligible for ASCT, defined as: >= 65 years old younger than 65 years but who reject the transplant procedure or with abnormal cardiac, pulmonary, hepatic and renal function defined as [1]: LVEF (left ventricular ejection fraction) < 40% FEV1 (forced expiratory volume-1 second) < 40% Bilirubin > 1.5 UNL, AST/ALT >2.5 UNL Creatinine clearance < 60 mL/min. Exclusion Criteria: Hypersensitivity to any active substance or to any of the excipients (lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, boron, mannitol, nitrogen, crospovidone, colloidal anhydrous silica, hypromellose, titanium dioxide, macrogol, talc, sodium starch glycolate, sodium benzoate, propylene glycol, sodium dihydrogen phosphate, hydroxypropyl beta cyclodextrin, sodium saccharin, sodium EDTA, sodium hydroxide, L-histidine, L-histidine hydrochloride monohydrate, L-methionine, polysorbate 20, sorbitol (E420), recombinant human hyaluronidase (rHuPH20)); Hereditary intolerance to fructose; Pregnant and lactating women; FBCP that do not follow the Pregnancy Prevention Plan requirements; Acute diffuse infiltrative pulmonary and pericardial disease; Acute viral infections (e.g. herpes simplex or ocular herpes simplex, herpes zoster, varicella); Systemic mycotic or bacterial infections, unless specific anti-infectious therapy is ongoing; Peptic ulcer; Psychosis; Administration of prophylactic vaccine from 8 to 2 weeks before starting treatment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alessandra Larocca, Dott.ssa
Phone
00390110243236
Email
clinical.trials@unito.it
Facility Information:
Facility Name
Dipartimento di Biotecnologie Molecolari e Scienze per la Salute
City
Torino
State/Province
TO
ZIP/Postal Code
10126
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alessandra Larocca, Dott.ssa
Phone
00390110243236
Email
clinical.trials@unito.it

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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