Ignite Creation Date:
2024-05-06 @ 3:51 PM
Last Modification Date:
2024-10-26 @ 1:58 PM
Study NCT ID:
NCT04785547
Status:
TERMINATED
Last Update Posted:
2024-01-16
First Post:
2021-03-01
Brief Title:
ALL SCTped 2012 FORUM Add-on Study Blina Post HSCT
Sponsor:
Prof Christina Peters
Organization:
St Anna Kinderkrebsforschung
Study Overview
Official Title:
A Phase II Study of Blincyto in Children With CD19 Precursor B-lineage ALL and MRD-Positivity Before andor Following First Allogeneic HSCT
Status:
TERMINATED
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated by Amgen Limited
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
An add-on phase II trial within the ALL SCTped 2012 FORUM with the primary objective to determine whether the use of Blincyto in paediatric patients with B-lineage ALL and pre- andor post-transplant MRD could induce MRD-negativity in patients who were MRD-positive before andor after allogeneic HSCT
The study protocol entitled A Phase II Study of Blincyto Blinatumomab in Children with CD19 B-lineage Acute Lymphoblastic Leukemia ALL and Minimal Residual Disease MRD-Positivity before or following first Allogeneic Hematopoetic Stem Cell Transplantation HSCT in complete remission CR1 CR2 CR3 was included in the ALL SCTped 2012 FORUM Protocol Appendix 1b
According to protocol 15 mcgm2day of Blincyto is given in continuous intravenous infusion over a 28-day cycle Starting day for patients who are MRD-positive before HSCT is between day 60 and day 100 and for patients who become MRD-positive post HSCT it is between day 60 and day 360 post HSCT
Patients are evaluated for response at day 28 4 days bone marrow morphology and MRD analysis - defined by PCRFLOW-techniques after start of Blincyto-treatment at the end of first Blincyto infusion and at regular post-TX-checks according to FORUM days 28 60 100 180 and 360 after HSCT
The protocol was approved in 10 countries Austria Belgium Czech Republic Denmark France Italy Norway Poland Slovakia and Spain participating ALL SCTped 2012 FORUM study Overall 3 patients were treated with Blincyto 2 in Oslo and 1 in Copenhagen
However the Investigator Initiated Research Agreement was terminated by Amgen on 26 April 2022 leading to an early termination of the study which was approved with the last protocol amendment
The study protocol entitled A Phase II Study of Blincyto Blinatumomab in Children with CD19 B-lineage Acute Lymphoblastic Leukemia ALL and Minimal Residual Disease MRD-Positivity before or following first Allogeneic Hematopoetic Stem Cell Transplantation HSCT in complete remission CR1 CR2 CR3 was included in the ALL SCTped 2012 FORUM Protocol Appendix 1b
According to protocol 15 mcgm2day of Blincyto is given in continuous intravenous infusion over a 28-day cycle Starting day for patients who are MRD-positive before HSCT is between day 60 and day 100 and for patients who become MRD-positive post HSCT it is between day 60 and day 360 post HSCT
Patients are evaluated for response at day 28 4 days bone marrow morphology and MRD analysis - defined by PCRFLOW-techniques after start of Blincyto-treatment at the end of first Blincyto infusion and at regular post-TX-checks according to FORUM days 28 60 100 180 and 360 after HSCT
The protocol was approved in 10 countries Austria Belgium Czech Republic Denmark France Italy Norway Poland Slovakia and Spain participating ALL SCTped 2012 FORUM study Overall 3 patients were treated with Blincyto 2 in Oslo and 1 in Copenhagen
However the Investigator Initiated Research Agreement was terminated by Amgen on 26 April 2022 leading to an early termination of the study which was approved with the last protocol amendment
Detailed Description:
621 Screening Pretreatment The screening process begins on the date the subject or legally acceptable representative signs the IRBEC approved ICF and assent form and continues until enrollment Informed consent and assent must be obtained before completing any study-specific procedures After written informed consent and assent have been obtained subjects will be screened in order to assess eligibility for study participation Only eligible subjects who meet the inclusionexclusion criteria listed in Section 4 will be enrolled in the study The total screening window is up to 14 days If a subject has not met all eligibility criteria at the end of the 14-day window the subject will be classified as a screen failure on the subject screening log Subjects who screen fail may be eligible to rescreen one time per Section 622
The following assessmentsprocedures are to be completed during the screening period at time points designated in the Schedule of Assessments
Confirmation that the Informed Consent Form and Assent Form have been signed
Product History Form for subjects who were enrolled in a previous Amgen Blincyto study
Relevant medical history including all data which are documented in FORUM trial
Review of inclusionexclusion criteria
Physical examination
Local laboratory assessments within 7 days prior to treatment start
Chemistry
Coagulation
Hematology CBC with differential
Bone marrow aspirate morphological and MRD assessment
Lumbar puncture
Serious Adverse Event reporting 622 Rescreening Subjects who are unable to complete or meet eligibility at the initial screening will be permitted to rescreen once provided study recruitment has not closed Upon signing a new Informed Consent Form and Assent Form a new 14-day screening window will begin Subjects will retain the same subject identification number assigned at the original screening
After reconsenting all screening procedures including the bone marrow aspirate must be repeated However previous bone marrow aspiratebiopsy taken within 14 days of the planned treatment start of Blincyto can be used to determine eligibility
623 Treatment The following procedures will be completed during day 1 to day 29 at the times designated in the Schedule of Assessments For assessments performed at day 1 all study procedures should be completed prior to the initiation of Blincyto therapy unless noted otherwise
Physical examination D1 of each treatment cycle prior to infusion start
Bone marrow aspiratebiopsy morphological and MRD assessment day 29 not mandatory in case of documented disease progression or relapse
Chemistry Coagulation Hematology Complete blood test CBC with differential
day 1 6h after the first dose of Blincyto
day 2 any time
day 3 any time
In addition hematology only day 29 not mandatory in case of documented disease progression or relapse
Immunoglobulins IgG only
Day 1 prior to infusion start
Day 29 after end of infusion
Vital signs pulse and temperature only at the following time points
Day 1 prior to infusion start
Day 15 and day 29 any time
Any other time as deemed necessary by the investigator per institutional guidelines
Neurological examination eg finger-nose andor writing test as appropriate for age
day 1 prior to infusion start
day 2 and day 3 any time
Any other time as deemed necessary by the investigator per institutional guidelines
Serious Adverse Event reporting 624 Safety Follow-up Visits End of Study Visit
All subjects including subjects who withdraw early should complete a safety follow-up visit 30 days 4 days after the last dose of Blincyto The following procedures will be completed at the visit
Physical examination
Local laboratory assessments
Chemistry
Coagulation
Hematology CBC with differential
Immunoglobulins IgG only
Urine or serum pregnancy test female adolescents of childbearing potential only if applicable
Serious Adverse Event reporting 625 Long-term Follow-up All subjects will be followed in the long-term follow-up portion of the study for OS
Subjects in remission will also be followed for duration of response Following the safety follow-up visit subjects will be followed every 6 months 2 weeks until 14 months after the first dose of Blincyto to assess disease status The following procedures will be completed for subjects who remain in remission
DiseaseSurvival status
Bone marrow aspiratebiopsy morphological and MRD assessment at day 180 post HSCT and day 360 post HSCT
Hematology neutrophils and platelets 626 Lumbar Puncture to Examine Cerebrospinal Fluid In case of clinical signs of CNS-disease a lumbar puncture will be performed as outlined in the Schedule of Assessments to assess for possible leukemic involvement of the CNS CSF cell count glucose and protein will be measured at the local laboratory as part of the examination Additional investigations of the CSF should be performed as clinically appropriate
If an Ommaya reservoir is in place and there is no evidence of blockage of CSF flow in the spinal canal withdrawal of a sample through the Ommaya reservoir is permitted
627 Bone Marrow Biopsy Aspiration
Bone marrow will be used for hematological assessment and for evaluation of MRD The following samples will be obtained for cytomorphological assessment and MRD measurement by a local laboratory
Cytomorphologypercentage of blasts bone marrow aspirates at screening at the end of each treatment cycle and every 6 months during long-term follow-up for subjects in remission only until relapse
MRD Aliquots at screening will be collected and analyzed Aliquots for each subsequent bone marrow assessment may be collected and analyzed if applicable
In case of insufficient quality of the bone marrow material at the end of each treatment cycle a repeat bone marrow assessment should be performed prior to treatment start in the next cycle or at the safety follow-up visit if the subject has not progressed and no further treatment cycles are to be administered
The degree of bone marrow infiltration defined by the percentage of leukemic blasts in bone marrow will be evaluated by local laboratories per cytomorphology and flow cytometry immunophenotyping During screening the B-precursor phenotype with CD19 positivity at least partial should be confirmed for inclusion
628 Laboratory Assessments The analytes for all laboratory tests used throughout this study are listed in the table below All screening and on-study laboratory samples will be collected and processed at the investigators local laboratory and analyzed locally Standard laboratory tests will be performed according to institutional guidelines The date and time of sample collection will be recorded in the source documents at the site Blood draws should not be done via the central venous access Exception If a permanent central line with more than one lumen is used blood draws can be done via the lumen that is not used for drug administration Any additional follow-up laboratory testing should be performed per standard of care for the treatment of ALL and according to ALL SCTped 2012 FORUM-study
Numeration as per protocol
The following assessmentsprocedures are to be completed during the screening period at time points designated in the Schedule of Assessments
Confirmation that the Informed Consent Form and Assent Form have been signed
Product History Form for subjects who were enrolled in a previous Amgen Blincyto study
Relevant medical history including all data which are documented in FORUM trial
Review of inclusionexclusion criteria
Physical examination
Local laboratory assessments within 7 days prior to treatment start
Chemistry
Coagulation
Hematology CBC with differential
Bone marrow aspirate morphological and MRD assessment
Lumbar puncture
Serious Adverse Event reporting 622 Rescreening Subjects who are unable to complete or meet eligibility at the initial screening will be permitted to rescreen once provided study recruitment has not closed Upon signing a new Informed Consent Form and Assent Form a new 14-day screening window will begin Subjects will retain the same subject identification number assigned at the original screening
After reconsenting all screening procedures including the bone marrow aspirate must be repeated However previous bone marrow aspiratebiopsy taken within 14 days of the planned treatment start of Blincyto can be used to determine eligibility
623 Treatment The following procedures will be completed during day 1 to day 29 at the times designated in the Schedule of Assessments For assessments performed at day 1 all study procedures should be completed prior to the initiation of Blincyto therapy unless noted otherwise
Physical examination D1 of each treatment cycle prior to infusion start
Bone marrow aspiratebiopsy morphological and MRD assessment day 29 not mandatory in case of documented disease progression or relapse
Chemistry Coagulation Hematology Complete blood test CBC with differential
day 1 6h after the first dose of Blincyto
day 2 any time
day 3 any time
In addition hematology only day 29 not mandatory in case of documented disease progression or relapse
Immunoglobulins IgG only
Day 1 prior to infusion start
Day 29 after end of infusion
Vital signs pulse and temperature only at the following time points
Day 1 prior to infusion start
Day 15 and day 29 any time
Any other time as deemed necessary by the investigator per institutional guidelines
Neurological examination eg finger-nose andor writing test as appropriate for age
day 1 prior to infusion start
day 2 and day 3 any time
Any other time as deemed necessary by the investigator per institutional guidelines
Serious Adverse Event reporting 624 Safety Follow-up Visits End of Study Visit
All subjects including subjects who withdraw early should complete a safety follow-up visit 30 days 4 days after the last dose of Blincyto The following procedures will be completed at the visit
Physical examination
Local laboratory assessments
Chemistry
Coagulation
Hematology CBC with differential
Immunoglobulins IgG only
Urine or serum pregnancy test female adolescents of childbearing potential only if applicable
Serious Adverse Event reporting 625 Long-term Follow-up All subjects will be followed in the long-term follow-up portion of the study for OS
Subjects in remission will also be followed for duration of response Following the safety follow-up visit subjects will be followed every 6 months 2 weeks until 14 months after the first dose of Blincyto to assess disease status The following procedures will be completed for subjects who remain in remission
DiseaseSurvival status
Bone marrow aspiratebiopsy morphological and MRD assessment at day 180 post HSCT and day 360 post HSCT
Hematology neutrophils and platelets 626 Lumbar Puncture to Examine Cerebrospinal Fluid In case of clinical signs of CNS-disease a lumbar puncture will be performed as outlined in the Schedule of Assessments to assess for possible leukemic involvement of the CNS CSF cell count glucose and protein will be measured at the local laboratory as part of the examination Additional investigations of the CSF should be performed as clinically appropriate
If an Ommaya reservoir is in place and there is no evidence of blockage of CSF flow in the spinal canal withdrawal of a sample through the Ommaya reservoir is permitted
627 Bone Marrow Biopsy Aspiration
Bone marrow will be used for hematological assessment and for evaluation of MRD The following samples will be obtained for cytomorphological assessment and MRD measurement by a local laboratory
Cytomorphologypercentage of blasts bone marrow aspirates at screening at the end of each treatment cycle and every 6 months during long-term follow-up for subjects in remission only until relapse
MRD Aliquots at screening will be collected and analyzed Aliquots for each subsequent bone marrow assessment may be collected and analyzed if applicable
In case of insufficient quality of the bone marrow material at the end of each treatment cycle a repeat bone marrow assessment should be performed prior to treatment start in the next cycle or at the safety follow-up visit if the subject has not progressed and no further treatment cycles are to be administered
The degree of bone marrow infiltration defined by the percentage of leukemic blasts in bone marrow will be evaluated by local laboratories per cytomorphology and flow cytometry immunophenotyping During screening the B-precursor phenotype with CD19 positivity at least partial should be confirmed for inclusion
628 Laboratory Assessments The analytes for all laboratory tests used throughout this study are listed in the table below All screening and on-study laboratory samples will be collected and processed at the investigators local laboratory and analyzed locally Standard laboratory tests will be performed according to institutional guidelines The date and time of sample collection will be recorded in the source documents at the site Blood draws should not be done via the central venous access Exception If a permanent central line with more than one lumen is used blood draws can be done via the lumen that is not used for drug administration Any additional follow-up laboratory testing should be performed per standard of care for the treatment of ALL and according to ALL SCTped 2012 FORUM-study
Numeration as per protocol
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None