Back to resultsVRD as Induction Followed by VR Maintenance in Patients With Newly Diagnosed High Risk Multiple Myeloma
Primary Purpose
Myeloma, Newly Diagnosed, High Risk
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
bortezomib
Lenalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Myeloma
Eligibility Criteria
Inclusion Criteria:
- Patient has a newly diagnosis of multiple myeloma
- Patient requires treatment for multiple myeloma
- Subject have high-risk characteristics.Our definition for high risk multiple myeloma :(1) with cytogenetic abnormalities including del(17p),t(4;14),t(14;16),and/or t(14;20) ;(2) R-ISS III；(3) ISS III and no complete remission is achieved before maintenance therapy.
- Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI
- Subject has a Karnofsky performance status ≥60%
- Subject has a life expectancy ≥ 3 months
- Subjects must meet the following laboratory parameters:
Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Hemoglobin ≥ 7 g/dL Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration) Serum SGOT/AST <3.0 x upper limits of normal (ULN) Serum SGPT/ALT <3.0 x upper limits of normal (ULN) Serum total bilirubin <2.0 mg/dL (34 µmol/L) Creatinine clearance ≥ 30 cc/min
Exclusion Criteria:
- Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning)
- Subject has a prior history of other malignancies unless disease-free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels
- Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI), Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Female subject who is pregnant or lactating
- Subject has known HIV infection
- Subject has known active hepatitis B or hepatitis C infection
- Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program
- Subject is unable to reliably take oral medications
- Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment
- Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Sites / Locations
- Sun Yat-sen University Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VRD for Followed by VR
Arm Description
The investigators gave patients subcutaneous bortezomib 1.3mg/m2 on days 1, 8,15, and 22; oral lenalidomide 25mg on days 1 to 21; and oral dexamethasone 40mg on days 1, 8, 15 and 12 of a 28-day cycle.Patients are allowed to proceed to stem-cell transplantation after four cycles of VRD at the discretion of the treating physician.Two months after hematologic recovery, nonprogressive patients are to receive consolidation therapy comprising two cycles of VRD.Patients who do not proceed to stem-cell transplantation receive more two induction cycles after obtaining maximum response but no less than six cycles totally. Responding patients could receive maintenance therapy comprising 4-week cycles of bortezomib 1.3mg/m2 on days 1 and 15 and lenalidomide on days 1 to 21 at the dose level of 10mg.
Outcomes
Primary Outcome Measures
Very good partial response or better by International Myeloma Working Group criteria
Number of participants with very good partial response or better as Assessed by International Myeloma Working Group criteria，change from baseline.
Secondary Outcome Measures
progression free survival
Duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.
overall survival
Duration from start of the treatment to death (regardless of cause of death).
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v 4.0
Number of participants with Treatment-Emergent Adverse Events as Assessed by CTCAE v 4.0，change from baseline
complete response rate by International Myeloma Working Group criteria
Number of participants with complete response as Assessed by International Myeloma Working Group criteria，change from baseline.
overall response rate by International Myeloma Working Group criteria
Number of participants with response (CR+VGPR+PR) as Assessed by International Myeloma Working Group criteria，change from baseline.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03641456
Brief Title
VRD as Induction Followed by VR Maintenance in Patients With Newly Diagnosed High Risk Multiple Myeloma
Official Title
Lenalidomide, Bortezomib, and Dexamethasone Combination Therapy as Induction Followed by Bortezomib and Lenalidomide Maintenance in Patients With Newly Diagnosed High Risk Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 25, 2020 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sun Yat-sen University
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
The phase 2 study evaluated the efficacy and safety of bortezomib in combination with lenalidomide as maintenance therapy in high risk newly diagnosed multiple myeloma patients who receive lenalidomide,bortezomib, and dexamethasone Combination as induction therapy.
Detailed Description
The aim of front-line therapy for multiple myeloma (MM) is to substantially decrease tumor burden, either in preparation for consolidation with high-dose melphalan therapy with autologous stem cell transplantation (ASCT) or as a means in itself to provide long-term disease control. The degree of disease reduction is associated with improved outcome, including prolonged progression-free survival (PFS) and overall survival (OS),both after preparation for or after consolidation with ASCT,and in patients not proceeding to ASCT.The introduction of the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide has been associated with improved survival. Combinations of bortezomib or lenalidomide with conventional anti-MM drugs have demonstrated very high overall response rates and quality of response in the front-line setting, as reviewed recently.The phase 2 study evaluated the efficacy and safety of bortezomib in combination with lenalidomide as maintenance therapy in high risk newly diagnosed multiple myeloma patients who receive lenalidomide, bortezomib, and dexamethasone(VRD) Combination as induction therapy.The investigators gave patients subcutaneous bortezomib on days 1, 8,15, and 22; oral lenalidomide on days 1 to 21; and oral dexamethasone on days 1, 8, 15 and 12 of a 28-day cycle.Patients are allowed to interrupt therapy for collection of stem cells at any time after three cycles of induction, and to proceed to stem-cell transplantation after four cycles of induction at the discretion of the treating physician.Two months after hematologic recovery, nonprogressive patients are to receive consolidation therapy comprising two 4-week cycles of VRD or the second autologous hematopoietic stem cell transplantation (determined by the attending physician according to the patient's physical condition, willingness and the number of CD34 + cells collected).Patients who do not proceed to stem-cell transplantation receive a total of 12 courses of VRD induction therapy(dexamethasone dosage will be reduced to 20mg from the 9th course of treatment). Responding patients could receive maintenance therapy comprising 4-week cycles of bortezomib on days 1 and 15 at the dose level of 1.3mg/m2 and lenalidomide on days 1 to 21 at the dose level of 10mg.Participants discontinued treatment if participants had progressive disease or unacceptable toxic eff ects not controlled with dose modifications.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myeloma, Newly Diagnosed, High Risk
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
VRD for Followed by VR
Arm Type
Experimental
Arm Description
The investigators gave patients subcutaneous bortezomib 1.3mg/m2 on days 1, 8,15, and 22; oral lenalidomide 25mg on days 1 to 21; and oral dexamethasone 40mg on days 1, 8, 15 and 12 of a 28-day cycle.Patients are allowed to proceed to stem-cell transplantation after four cycles of VRD at the discretion of the treating physician.Two months after hematologic recovery, nonprogressive patients are to receive consolidation therapy comprising two cycles of VRD.Patients who do not proceed to stem-cell transplantation receive more two induction cycles after obtaining maximum response but no less than six cycles totally. Responding patients could receive maintenance therapy comprising 4-week cycles of bortezomib 1.3mg/m2 on days 1 and 15 and lenalidomide on days 1 to 21 at the dose level of 10mg.
Intervention Type
Drug
Intervention Name(s)
bortezomib
Other Intervention Name(s)
Velcade
Intervention Description
The investigators gave patients subcutaneous bortezomib 1.3mg/m2 on days 1, 8,15, and 22 of a 28-day cycle. More two induction cycles after obtaining maximum response but no less than six cycles totally.Responding patients could receive maintenance therapy comprising 4-week cycles of bortezomib on days 1 and 15 at the dose level of 1.3mg/m2. Patients discontinued treatment if they had progressive disease or or unacceptable toxic effects not controlled with dose modifications.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
The investigators gave patients oral lenalidomide 25mg on days 1 to 21 of a 28-day cycle. More two induction cycles after obtaining maximum response but no less than six cycles totally.Responding patients could receive maintenance therapy comprising 4-week cycles of lenalidomide on days 1 to 21 at the dose level of 10mg. Patients discontinued treatment if they had progressive disease or unacceptable toxic effects not controlled with dose modifications.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Dexamethasone Acetate
Intervention Description
The investigators gave patients oral dexamethasone 40mg on days 1, 8, 15 and 22 of a 28-day cycle. More two induction cycles after obtaining maximum response but no less than six cycles totally.
Primary Outcome Measure Information:
Title
Very good partial response or better by International Myeloma Working Group criteria
Description
Number of participants with very good partial response or better as Assessed by International Myeloma Working Group criteria，change from baseline.
Time Frame
up to end of follow-up-phase (approximately 3 years)
Secondary Outcome Measure Information:
Title
progression free survival
Description
Duration from start of the treatment to disease progression or death (regardless of cause of death), whichever comes first.
Time Frame
up to end of follow-up-phase (approximately 3 years)
Title
overall survival
Description
Duration from start of the treatment to death (regardless of cause of death).
Time Frame
up to end of follow-up-phase (approximately 3 years)
Title
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v 4.0
Description
Number of participants with Treatment-Emergent Adverse Events as Assessed by CTCAE v 4.0，change from baseline
Time Frame
up to end of follow-up-phase (approximately 3 years)
Title
complete response rate by International Myeloma Working Group criteria
Description
Number of participants with complete response as Assessed by International Myeloma Working Group criteria，change from baseline.
Time Frame
up to end of follow-up-phase (approximately 3 years)
Title
overall response rate by International Myeloma Working Group criteria
Description
Number of participants with response (CR+VGPR+PR) as Assessed by International Myeloma Working Group criteria，change from baseline.
Time Frame
up to end of follow-up-phase (approximately 3 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient has a newly diagnosis of multiple myeloma
Patient requires treatment for multiple myeloma
Subject have high-risk characteristics.Our definition for high risk multiple myeloma :(1) with cytogenetic abnormalities including del(17p),t(4;14),t(14;16),and/or t(14;20) ;(2) R-ISS III；(3) ISS III and no complete remission is achieved before maintenance therapy.
Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI
Subject has a Karnofsky performance status ≥60%
Subject has a life expectancy ≥ 3 months
Subjects must meet the following laboratory parameters:
Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Hemoglobin ≥ 7 g/dL Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration) Serum SGOT/AST <3.0 x upper limits of normal (ULN) Serum SGPT/ALT <3.0 x upper limits of normal (ULN) Serum total bilirubin <2.0 mg/dL (34 µmol/L) Creatinine clearance ≥ 30 cc/min
Exclusion Criteria:
Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning)
Subject has a prior history of other malignancies unless disease-free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels
Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI), Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Female subject who is pregnant or lactating
Subject has known HIV infection
Subject has known active hepatitis B or hepatitis C infection
Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program
Subject is unable to reliably take oral medications
Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment
Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hua wang, MD.
Phone
020-87342462
Email
wanghua@sysucc.org.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hua Wang, MD.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hua Wang, MD.
Organizational Affiliation
Sun Yat-sen University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sun Yat-sen University Cancer Center
City
GuangZhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhongjun Xia, MD.
Phone
0086-02087342438
Email
zhongjunxia_64@sina.com
12. IPD Sharing Statement
Learn more about this trial
VRD as Induction Followed by VR Maintenance in Patients With Newly Diagnosed High Risk Multiple Myeloma
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