Ignite Creation Date:
2024-05-06 @ 9:37 AM
Last Modification Date:
2024-10-26 @ 12:16 PM
Study NCT ID:
NCT03023527
Status:
TERMINATED
Last Update Posted:
2018-05-23
First Post:
2017-01-11
Brief Title:
Nivolumab Role in the Treatment of Patients With Refractory or Relapse Multiple Myeloma
Sponsor:
PETHEMA Foundation
Organization:
PETHEMA Foundation
Study Overview
Official Title:
None
Status:
TERMINATED
Status Verified Date:
2018-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Safety
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open-label non-randomized Phase 1 study evaluating the role of two regimens
A Nivolumab in combination with Pomalidomide and low dose dexamethasone and B Nivolumab Elotuzumab Pomalidomide dexamethasone in the treatment of relapse or refractory multiple myeloma patients
The study will be performed in 10 sites in Spain First the MTD for the Nivo-Pom-Dex combination will be determined using a 33 scheme Once the MTD has been determined both Regimes A and B will be open for full accrual and patients will be included in an alternating way in both regimes simultaneously In the case that an unacceptable toxicity was seen in the Lead-in phase Nivolumab Pomalidomide low dose dexamethasone the other phase would not be open
A safety analysis by an internal review committee will be performed once the first six patients included in the regimen B have completed the first two cycles
The main purpose of the study is to analyze the proportion of subjects with refractory or relapsed multiple myeloma receiving the combination Nivo-Pom-dex or Nivo-Pom-dex-Elo experience one or more haematological and non haematological SAE grade 3 or higher
Additionally other
Research Hypothesis
The combination of nivolumab with pomalidomide and dexamethasone will demonstrate adequate safety and tolerability to permit further testing of these combinations in subjects with multiple myeloma The addition of elotuzumab to nivolumab pomalidomide and dexamethasone will not change the safety profile
Duration of Study
The study will remain open for enrolment for 15 months estimated or until the planned total number of 40 subjects is reached if this happens first
The follow-up of the last recruited patient will be up to 3 years being the Final analyses performed 15 years after the last patient is included
Study Population
Male and female adult patients with Multiple Myeloma in first or subsequent relapses previously exposed to both a proteasome inhibitor and a IMID Lenalidomide Patients may be exposed relapsed or refractory to Lenalidomide
A Nivolumab in combination with Pomalidomide and low dose dexamethasone and B Nivolumab Elotuzumab Pomalidomide dexamethasone in the treatment of relapse or refractory multiple myeloma patients
The study will be performed in 10 sites in Spain First the MTD for the Nivo-Pom-Dex combination will be determined using a 33 scheme Once the MTD has been determined both Regimes A and B will be open for full accrual and patients will be included in an alternating way in both regimes simultaneously In the case that an unacceptable toxicity was seen in the Lead-in phase Nivolumab Pomalidomide low dose dexamethasone the other phase would not be open
A safety analysis by an internal review committee will be performed once the first six patients included in the regimen B have completed the first two cycles
The main purpose of the study is to analyze the proportion of subjects with refractory or relapsed multiple myeloma receiving the combination Nivo-Pom-dex or Nivo-Pom-dex-Elo experience one or more haematological and non haematological SAE grade 3 or higher
Additionally other
Research Hypothesis
The combination of nivolumab with pomalidomide and dexamethasone will demonstrate adequate safety and tolerability to permit further testing of these combinations in subjects with multiple myeloma The addition of elotuzumab to nivolumab pomalidomide and dexamethasone will not change the safety profile
Duration of Study
The study will remain open for enrolment for 15 months estimated or until the planned total number of 40 subjects is reached if this happens first
The follow-up of the last recruited patient will be up to 3 years being the Final analyses performed 15 years after the last patient is included
Study Population
Male and female adult patients with Multiple Myeloma in first or subsequent relapses previously exposed to both a proteasome inhibitor and a IMID Lenalidomide Patients may be exposed relapsed or refractory to Lenalidomide
Detailed Description:
Test Product Dose and Mode of Administration Duration of Treatment
The study is using a modified 33 design and has 2 parts First Lead-In phase the MTD for the Nivo-Pom-dex combination will be determined
Regimen A The treatment regimen will include Pomalidomide Nivolumab and low dose dexamethasone There will be three different dose levels
First dose level DL1 Nivolumab 240mg intravenous infusion every other week Pomalidomide at the standard dose of 4 mgday from day 1 to 21 in a 28-day cycle and Dexamethasone 40mg weekly except for patients older than 75 or with comorbidities who will received 20 mg weekly
Initially 3 patients will be enrolled and treated If not DLT 3 additional patients will be included at the same dose level
In the case there is DLT the dose level will be de-escalated
If the DLT is haematological or non-hematological attributable to Pomalidomide the dose level will be DL-1P Pomalidomide 2 mgd from day 1-21 Nivolumab 240mg every other week and Dexamethasone 40mg weekly or 20 weekly in patients older than 75 or with comorbidities
In the case the DLT is non-hematological and attributable to Nivolumab this combination arm will be stopped No Nivolumab dose reductions are allowed in the trial
Once the MTD has been determined both regimens A and B will be open for full accrual and patients will be included in an alternating way in both regimens simultaneously
Regimen B The treatment regimen will include Pomalidomide and Nivolumab at the selected dose level from the previous arm of the study Dexamethasone will be given in the standard dose of 40mg weekly on days 1 8 15 and 22 of each 28-day cycle and could be reduced to 20mg weekly in case of age above 75 year-old or comorbidities Elotuzumab will be given at the standard dose of 10mgkg weekly for the first two cycles and then on days 1 and 15 for the subsequent cycles
Treatment will be maintained until disease progression
Criteria for Evaluation
Safety Adverse events will be assessed continuously during the study and for 100 days after the last treatment Adverse events will be coded using the most current version of MedDRA and reviewed for potential significance and importance Adverse events will be evaluated according to the NCI CTCAE Version 40 Subjects should be followed until all treatment related adverse events have recovered to grade 1 or baseline or are deemed irreversible by the investigator Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements ECGs physical examinations and clinical laboratory tests
Efficacy Disease assessment will be performed with serum and urine myeloma lab tests bone marrow assessment and computed tomography CT andor magnetic resonance imaging MRI as appropriate Myeloma responses will be based on investigator assessment and determined as defined by IMWG criteria Any initial assessment will be confirmed by a repeat evaluation every 4 weeks
Biomarker Assessments Peripheral blood and bone marrow samples will be collected from subjects to assess mechanisms of primary resistance cell surface protein analyses and transcriptome analyses and mechanisms of chemosensitivity to NivoPomDex combination 10-colour flow cytometry TCR clonality by NGS
The study is using a modified 33 design and has 2 parts First Lead-In phase the MTD for the Nivo-Pom-dex combination will be determined
Regimen A The treatment regimen will include Pomalidomide Nivolumab and low dose dexamethasone There will be three different dose levels
First dose level DL1 Nivolumab 240mg intravenous infusion every other week Pomalidomide at the standard dose of 4 mgday from day 1 to 21 in a 28-day cycle and Dexamethasone 40mg weekly except for patients older than 75 or with comorbidities who will received 20 mg weekly
Initially 3 patients will be enrolled and treated If not DLT 3 additional patients will be included at the same dose level
In the case there is DLT the dose level will be de-escalated
If the DLT is haematological or non-hematological attributable to Pomalidomide the dose level will be DL-1P Pomalidomide 2 mgd from day 1-21 Nivolumab 240mg every other week and Dexamethasone 40mg weekly or 20 weekly in patients older than 75 or with comorbidities
In the case the DLT is non-hematological and attributable to Nivolumab this combination arm will be stopped No Nivolumab dose reductions are allowed in the trial
Once the MTD has been determined both regimens A and B will be open for full accrual and patients will be included in an alternating way in both regimens simultaneously
Regimen B The treatment regimen will include Pomalidomide and Nivolumab at the selected dose level from the previous arm of the study Dexamethasone will be given in the standard dose of 40mg weekly on days 1 8 15 and 22 of each 28-day cycle and could be reduced to 20mg weekly in case of age above 75 year-old or comorbidities Elotuzumab will be given at the standard dose of 10mgkg weekly for the first two cycles and then on days 1 and 15 for the subsequent cycles
Treatment will be maintained until disease progression
Criteria for Evaluation
Safety Adverse events will be assessed continuously during the study and for 100 days after the last treatment Adverse events will be coded using the most current version of MedDRA and reviewed for potential significance and importance Adverse events will be evaluated according to the NCI CTCAE Version 40 Subjects should be followed until all treatment related adverse events have recovered to grade 1 or baseline or are deemed irreversible by the investigator Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements ECGs physical examinations and clinical laboratory tests
Efficacy Disease assessment will be performed with serum and urine myeloma lab tests bone marrow assessment and computed tomography CT andor magnetic resonance imaging MRI as appropriate Myeloma responses will be based on investigator assessment and determined as defined by IMWG criteria Any initial assessment will be confirmed by a repeat evaluation every 4 weeks
Biomarker Assessments Peripheral blood and bone marrow samples will be collected from subjects to assess mechanisms of primary resistance cell surface protein analyses and transcriptome analyses and mechanisms of chemosensitivity to NivoPomDex combination 10-colour flow cytometry TCR clonality by NGS
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