Ignite Creation Date:
2024-10-26 @ 3:37 PM
Last Modification Date:
2024-10-26 @ 3:37 PM
Study NCT ID:
NCT06547866
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-30
Brief Title:
Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Open Label Phase 2 Study Evaluating the Efficacy and Tolerance of a Zanubrutinib and BGB-11417 Combination in Patients Previously Treated for Waldenström Macroglobulinemia
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
WAZABI
Brief Summary:
This is a French multicenter open label non-randomized Phase II trial evaluating the efficacy and tolerance of a combination of oral zanubrutinib and BGB-11417 in subjects aged 18 years and older with previously treated Waldenström macroglobulinemia WM who require therapy according to the consensus panel criteria from the Second International Workshop on Waldenströms macroglobulinemia
population Patients with previously treated Waldenstrom macroglobulinemia
The investigational medicinal products IMP are Zanubrutinib BGB- 3111 and BGB-11417Treatment will be administered for a total of twenty 28 day cycles
Cycle 1 with zanubrutinib only
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
cycle 2 day 1 10mg
cycle 2 day 2 20 mg
cycle 2 day 3 40mg
cycle 2 day 4-7 80md daily
cycle 2 day 8 and beyond 160 mg daily
Cycles 3-20 with zanubrutinib plus BGB-11417 full dose
population Patients with previously treated Waldenstrom macroglobulinemia
The investigational medicinal products IMP are Zanubrutinib BGB- 3111 and BGB-11417Treatment will be administered for a total of twenty 28 day cycles
Cycle 1 with zanubrutinib only
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
cycle 2 day 1 10mg
cycle 2 day 2 20 mg
cycle 2 day 3 40mg
cycle 2 day 4-7 80md daily
cycle 2 day 8 and beyond 160 mg daily
Cycles 3-20 with zanubrutinib plus BGB-11417 full dose
Detailed Description:
study design Open label multicenter phase 2 trial
population Patients with previously treated Waldenstrom macroglobulinemia
Primary objective
To evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RefractoryRelapsing RR WM by the proportion of subjects achieving either a Complete Response CR or Very Good Partial Responses VGPRduration of time in Refractoryrelapsing RR Waldenstrom macroglobulinemia WM
Secondary objectives
To further evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RR WM
To determine the incidence and severity of serum M-protein monoclonal IgM rebound after planned cessation of the combination of zanubrutinib and BGB-11417-101 in RR WM
To evaluate the safety and tolerability of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RR WM
Sample size 102 patients Length of study Inclusion period 24 months Treatment duration 18 months twenty 28-days cycles Follow-up period 3 years
Study treatment
The investigational medicinal products IMP are Zanubrutinib BGB- 3111 and BGB-11417Treatment will be administered for a total of twenty 28 day cycles
Cycle 1 with zanubrutinib only
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
cycle 2 day 1 10mg
cycle 2 day 2 20 mg
cycle 2 day 3 40mg
cycle 2 day 4-7 80md daily
cycle 2 day 8 and beyond 160 mg daily
Cycles 3-20 with zanubrutinib plus BGB-11417 full dose
All patient will receive both drugs
Study procedures
Screening period
Assessments may be done up to 28 days before the treatment start and will include
Clinical assessments
- Medical history WM history including prior treatment lines previous IPSS WM score histology known cytogenetics and molecular features including MYD88 CXCR4 and TP53 mutational status
Concomitant therapies
Complete physical examination including weight height vital signs ECOG performance status B symptoms detailed evaluation of lymph nodes liver and spleen and infection monitoring including COVID-19 nasal test
IPSS WM score
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood coagulation tests including prothrombin time activated cephalin time fibrinogen von Willebrand factor vWF including vWF antigen vWFAg and vWFActivity WFAct evaluation according to ABO blood group and FVIII If acquired Willebrand syndrome according to hemorrhagic risk assessment further analysis is encouraged
Blood chemistry tests including sodium potassium chloride bicarbonate fasting glucose phosphate blood urea nitrogen BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin alanine aminotransferase ALAT aspartate aminotransferase ASAT lactate dehydrogenase LDH alkaline phosphatase PAL uric acid C-reactive protein CRP beta2microglobulin and pregnancy test
Troponin NT-proBNP will be performed on blood
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 immunofixation nephelometry free light chains kappa and lambda cryoglobulinemia
IgG IgA and IgM levels
Serologies for HBV HCV and HIV
Cardiovascular assessments
Cardiovascular evaluation by investigator
o 12-lead ECG and QTc calculation
o blood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
Cardiovascular evaluation by cardiologist
12-lead ECG with QTc calculation
echocardiography
24h Holter ECG monitoring
24h Ambulatory blood pressure monitoring ABPM
Imaging assessments
-Whole-Body CT scan neck thorax abdomen pelvis with tumor measurements
Specific assessments
BM biopsy local laboratory
This can be omitted if already done within the past 3 months
BM aspirate for oLocal laboratory for Cytogenetic analysis and FISH for 17p oFILOthèque central laboratory storage for future analysis unsorted and CD19 sorted cells for mutational profile
Blood MRD assessment on plasmatic cell-free tumor DNA FILOthèque central laboratory
Treatment period
Clinical assessment
Concomitant therapies and adverse events severe adverse events and adverse events of special interest AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator after 1 3 6 9 12 15 and 18 cycles o12-lead ECG and QTc calculation oblood pressure after a 5 minute rest average of 3 measurements separated by 1 minute
The 12-lead ECG by investigator is not mandatory if already done or planned during the cardiology consultation within one month at cycle 3 6 12 and 18
-Cardiovascular evaluation by cardiologist after 3 6 12 and 18 cycles ocardiology consultation o24h Holter ECG monitoring o24h ABPM oEchocardiography
24h Holter ECG will be repeated only at cycles 3 6 and 18 only risk patient
24h ABMP will be repeated only at cycles 3 12 and 18
Echocardiography will be repeated at cycle 18
Biological assessments at day 1 - 7 days of each cycle
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry including sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP and pregnancy test
During ramp up period serum creatinine sodium potassium chloride bicarbonate calcemia phosphoremia LDH is mandatory before initiation of any ramp up dose of BGB-11417 and 8 and 24 hours after drug intake
Troponin and NT-proBNP at cycles 1 3 6 9 12 15 and 18
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm CR
IgG IgA and IgM levels
Imaging assessments
-Whole-body CT scan neck thorax abdomen pelvis every 24 weeks 6 cycles ie after cycles 3 6 12 and 18 in all subjects who had measurable nodalextranodal disease at screening
Specific assessments
-FILOthèque central laboratory Blood on specific tube for MRD assessment on plasmatic cell-free tumor DNA at cycles 3 6 12 and 18 storage
Response evaluation
Throughout the treatment period especially before end of treatment EOT 3 months EVAL 2 evaluation
if a CR is suspected negative IF an unscheduled CT scan should be done followed by biological evaluations including BM biopsy local laboratory to confirm CR
If a VGPR is suspected 90 reduction in serum M-protein monoclonal IgM level from baseline but still detectable and decreased lymphadenopathy splenomegaly if present at baseline an unscheduled CT scan should be done to confirm VGPR
Evaluation 1 EVAL 1 1 month after the end of treatment This evaluation takes place 1 month after EOT either after completion of cycle 20 or after the last cycle in case of early discontinuation This evaluation may detect M-protein rebound with or without other features of early progression
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oBlood pressure after a 5 minute rest average of 3 measurements separated by 1 minute
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP and pregnancy test
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Evaluation 2 EVAL 2 3 months after the end of treatment This evaluation takes place 3 months after EOT either after completion of cycle 20 or after the last cycle in case of early discontinuation This evaluation may detect M-protein rebound with or without other features of early progression
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oBlood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
-Cardiovascular evaluation by a cardiologist oCardiology consultation o24h Ambulatory blood pressure monitoring ABPM oEchocardiography
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP
NT-proBNP
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Imaging and BM assessments
Whole body CT scan
BM biopsy local laboratory if not performed during the treatment period for CR or progression
BM aspirate FILOthèque central laboratory for storage and analysis for molecular studies without CD19 sorting
Blood collected on specific tube FILOthèque central laboratory for assessment of plasmatic cell-free tumor DNA
Evaluation in case of suspected CR At any time throughout the study especially before EOT evaluation when a CR is suspected based on a negative immunofixation an additional evaluation should be realized in order to confirm the CR
This additional evaluation includes primarily
Repeated screening for cryoglobulinemia in patients known to have significant cryoglobulinemia at screening
CT scan
Then if both immunofixation and CT scan are consistent with CR a biological assessment should be scheduled with
-BM biopsy local laboratory
Evaluation in case of suspected VGPR At any time throughout the study especially before EOT evaluation when a VGPR is suspected based on 90 reduction in M-protein monoclonal IgM level from baseline but still detectable and decreased lymphadenopathysplenomegaly if present at baseline an additional evaluation should be realized in order to confirm the VGPR
This additional evaluation includes
Repeated screening for cryoglobulinemia in patients known to have significant cryoglobulinemia at screening
CT scan to confirm the reduction of deep-seated lymphadenopathy and splenomegaly if present at baseline
Evaluation in case of progression during treatment and follow-up period
BM biopsy optional local laboratory
BM aspirate indicated according to study only in case of progression for
local laboratory cytogenetics and FISH for 17p
FILOthèque central laboratory storage of unsorted and CD19 sorted cells for molecular analyzes
Blood collected on specific tube for assessment of plasmatic cell-free tumor DNA FILOthèque central laboratory
Post-treatment follow-up period after EVAL 2 Two follow-up evaluations scheduled at 1 month EVAL 1 and at 3 months EVAL 2 have been already detailed above Thereafter all patients enrolled in the study will be followed until progression or death every 3 months the first year FU6 FU9 and FU12 then every 6 months for a total follow up period of three years FU18 FU24 FU30 and FU36
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination evaluation of lymph nodes liver and spleen
Cardiovascular assessments
Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oblood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
Cardiovascular evaluation by a cardiologist only at FU36 ocardiology consultation o24h ABPM oEchocardiography
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP
NT-proBNP only FU36
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Imaging and BM assessments
Whole body CT scan if clinically indicated especially in case of progression
BM biopsy local laboratory
BM aspirate indicated according to study only in case of progression
Premature end of treatment PEOT A visit will be performed 4 weeks EVAL 1 and 3 months EVAL 2 after the last treatment day for patients who discontinue treatment prematurely and for patients withdrawing their consent if possible
In case of PEOT for disease progression patients will be evaluated
End of study EOS The end of study becomes effective after the end of the last study visit of the last patient enrolled once the FU36 visit has been achieved The end of study visit corresponds to the last follow-up visit FU36 For patients withdrawing consent during the follow up period no end of study visit is required
Observational study For all patients if they consent the survival data will be collected every year for an observational study in the e-CRF Survival date andor event date until death for OS analysis
population Patients with previously treated Waldenstrom macroglobulinemia
Primary objective
To evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RefractoryRelapsing RR WM by the proportion of subjects achieving either a Complete Response CR or Very Good Partial Responses VGPRduration of time in Refractoryrelapsing RR Waldenstrom macroglobulinemia WM
Secondary objectives
To further evaluate the efficacy of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RR WM
To determine the incidence and severity of serum M-protein monoclonal IgM rebound after planned cessation of the combination of zanubrutinib and BGB-11417-101 in RR WM
To evaluate the safety and tolerability of a combination of zanubrutinib and BGB-11417 given for a limited duration of time in RR WM
Sample size 102 patients Length of study Inclusion period 24 months Treatment duration 18 months twenty 28-days cycles Follow-up period 3 years
Study treatment
The investigational medicinal products IMP are Zanubrutinib BGB- 3111 and BGB-11417Treatment will be administered for a total of twenty 28 day cycles
Cycle 1 with zanubrutinib only
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
Cycle 2 with zanubrutinib plus BGB-11417 ramp-up
cycle 2 day 1 10mg
cycle 2 day 2 20 mg
cycle 2 day 3 40mg
cycle 2 day 4-7 80md daily
cycle 2 day 8 and beyond 160 mg daily
Cycles 3-20 with zanubrutinib plus BGB-11417 full dose
All patient will receive both drugs
Study procedures
Screening period
Assessments may be done up to 28 days before the treatment start and will include
Clinical assessments
- Medical history WM history including prior treatment lines previous IPSS WM score histology known cytogenetics and molecular features including MYD88 CXCR4 and TP53 mutational status
Concomitant therapies
Complete physical examination including weight height vital signs ECOG performance status B symptoms detailed evaluation of lymph nodes liver and spleen and infection monitoring including COVID-19 nasal test
IPSS WM score
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood coagulation tests including prothrombin time activated cephalin time fibrinogen von Willebrand factor vWF including vWF antigen vWFAg and vWFActivity WFAct evaluation according to ABO blood group and FVIII If acquired Willebrand syndrome according to hemorrhagic risk assessment further analysis is encouraged
Blood chemistry tests including sodium potassium chloride bicarbonate fasting glucose phosphate blood urea nitrogen BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin alanine aminotransferase ALAT aspartate aminotransferase ASAT lactate dehydrogenase LDH alkaline phosphatase PAL uric acid C-reactive protein CRP beta2microglobulin and pregnancy test
Troponin NT-proBNP will be performed on blood
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 immunofixation nephelometry free light chains kappa and lambda cryoglobulinemia
IgG IgA and IgM levels
Serologies for HBV HCV and HIV
Cardiovascular assessments
Cardiovascular evaluation by investigator
o 12-lead ECG and QTc calculation
o blood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
Cardiovascular evaluation by cardiologist
12-lead ECG with QTc calculation
echocardiography
24h Holter ECG monitoring
24h Ambulatory blood pressure monitoring ABPM
Imaging assessments
-Whole-Body CT scan neck thorax abdomen pelvis with tumor measurements
Specific assessments
BM biopsy local laboratory
This can be omitted if already done within the past 3 months
BM aspirate for oLocal laboratory for Cytogenetic analysis and FISH for 17p oFILOthèque central laboratory storage for future analysis unsorted and CD19 sorted cells for mutational profile
Blood MRD assessment on plasmatic cell-free tumor DNA FILOthèque central laboratory
Treatment period
Clinical assessment
Concomitant therapies and adverse events severe adverse events and adverse events of special interest AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator after 1 3 6 9 12 15 and 18 cycles o12-lead ECG and QTc calculation oblood pressure after a 5 minute rest average of 3 measurements separated by 1 minute
The 12-lead ECG by investigator is not mandatory if already done or planned during the cardiology consultation within one month at cycle 3 6 12 and 18
-Cardiovascular evaluation by cardiologist after 3 6 12 and 18 cycles ocardiology consultation o24h Holter ECG monitoring o24h ABPM oEchocardiography
24h Holter ECG will be repeated only at cycles 3 6 and 18 only risk patient
24h ABMP will be repeated only at cycles 3 12 and 18
Echocardiography will be repeated at cycle 18
Biological assessments at day 1 - 7 days of each cycle
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry including sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP and pregnancy test
During ramp up period serum creatinine sodium potassium chloride bicarbonate calcemia phosphoremia LDH is mandatory before initiation of any ramp up dose of BGB-11417 and 8 and 24 hours after drug intake
Troponin and NT-proBNP at cycles 1 3 6 9 12 15 and 18
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm CR
IgG IgA and IgM levels
Imaging assessments
-Whole-body CT scan neck thorax abdomen pelvis every 24 weeks 6 cycles ie after cycles 3 6 12 and 18 in all subjects who had measurable nodalextranodal disease at screening
Specific assessments
-FILOthèque central laboratory Blood on specific tube for MRD assessment on plasmatic cell-free tumor DNA at cycles 3 6 12 and 18 storage
Response evaluation
Throughout the treatment period especially before end of treatment EOT 3 months EVAL 2 evaluation
if a CR is suspected negative IF an unscheduled CT scan should be done followed by biological evaluations including BM biopsy local laboratory to confirm CR
If a VGPR is suspected 90 reduction in serum M-protein monoclonal IgM level from baseline but still detectable and decreased lymphadenopathy splenomegaly if present at baseline an unscheduled CT scan should be done to confirm VGPR
Evaluation 1 EVAL 1 1 month after the end of treatment This evaluation takes place 1 month after EOT either after completion of cycle 20 or after the last cycle in case of early discontinuation This evaluation may detect M-protein rebound with or without other features of early progression
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oBlood pressure after a 5 minute rest average of 3 measurements separated by 1 minute
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP and pregnancy test
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Evaluation 2 EVAL 2 3 months after the end of treatment This evaluation takes place 3 months after EOT either after completion of cycle 20 or after the last cycle in case of early discontinuation This evaluation may detect M-protein rebound with or without other features of early progression
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination including evaluation of lymph nodes liver and spleen
Cardiovascular assessments
-Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oBlood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
-Cardiovascular evaluation by a cardiologist oCardiology consultation o24h Ambulatory blood pressure monitoring ABPM oEchocardiography
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP
NT-proBNP
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Imaging and BM assessments
Whole body CT scan
BM biopsy local laboratory if not performed during the treatment period for CR or progression
BM aspirate FILOthèque central laboratory for storage and analysis for molecular studies without CD19 sorting
Blood collected on specific tube FILOthèque central laboratory for assessment of plasmatic cell-free tumor DNA
Evaluation in case of suspected CR At any time throughout the study especially before EOT evaluation when a CR is suspected based on a negative immunofixation an additional evaluation should be realized in order to confirm the CR
This additional evaluation includes primarily
Repeated screening for cryoglobulinemia in patients known to have significant cryoglobulinemia at screening
CT scan
Then if both immunofixation and CT scan are consistent with CR a biological assessment should be scheduled with
-BM biopsy local laboratory
Evaluation in case of suspected VGPR At any time throughout the study especially before EOT evaluation when a VGPR is suspected based on 90 reduction in M-protein monoclonal IgM level from baseline but still detectable and decreased lymphadenopathysplenomegaly if present at baseline an additional evaluation should be realized in order to confirm the VGPR
This additional evaluation includes
Repeated screening for cryoglobulinemia in patients known to have significant cryoglobulinemia at screening
CT scan to confirm the reduction of deep-seated lymphadenopathy and splenomegaly if present at baseline
Evaluation in case of progression during treatment and follow-up period
BM biopsy optional local laboratory
BM aspirate indicated according to study only in case of progression for
local laboratory cytogenetics and FISH for 17p
FILOthèque central laboratory storage of unsorted and CD19 sorted cells for molecular analyzes
Blood collected on specific tube for assessment of plasmatic cell-free tumor DNA FILOthèque central laboratory
Post-treatment follow-up period after EVAL 2 Two follow-up evaluations scheduled at 1 month EVAL 1 and at 3 months EVAL 2 have been already detailed above Thereafter all patients enrolled in the study will be followed until progression or death every 3 months the first year FU6 FU9 and FU12 then every 6 months for a total follow up period of three years FU18 FU24 FU30 and FU36
Clinical assessments
Concomitant therapies
AE SAE and AESI
Complete physical examination evaluation of lymph nodes liver and spleen
Cardiovascular assessments
Cardiovascular evaluation by investigator o12-lead ECG and QTc calculation oblood pressure after 5 minutes rest average of 3 measurements separated by 1 minute
Cardiovascular evaluation by a cardiologist only at FU36 ocardiology consultation o24h ABPM oEchocardiography
Biological assessments
Standard hematology tests including CBC hemoglobin WBC count absolute differential count platelet count
Blood chemistry sodium potassium chloride bicarbonate fasting glucose phosphate BUN creatinine calcium phosphate magnesium total direct and indirect bilirubin total protein albumin ALAT ASAT LDH PAL uric acid CRP
NT-proBNP only FU36
Serum M-protein monoclonal IgM quantification based on protein electrophoresis or alternate methods according to appendix 3 with additional immunofixation to confirm a CR
IgG IgA and IgM levels
Imaging and BM assessments
Whole body CT scan if clinically indicated especially in case of progression
BM biopsy local laboratory
BM aspirate indicated according to study only in case of progression
Premature end of treatment PEOT A visit will be performed 4 weeks EVAL 1 and 3 months EVAL 2 after the last treatment day for patients who discontinue treatment prematurely and for patients withdrawing their consent if possible
In case of PEOT for disease progression patients will be evaluated
End of study EOS The end of study becomes effective after the end of the last study visit of the last patient enrolled once the FU36 visit has been achieved The end of study visit corresponds to the last follow-up visit FU36 For patients withdrawing consent during the follow up period no end of study visit is required
Observational study For all patients if they consent the survival data will be collected every year for an observational study in the e-CRF Survival date andor event date until death for OS analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None