Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT04785547 |
| Other study ID # |
FORUM Add-on Blina post TX |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
December 17, 2020 |
| Est. completion date |
January 22, 2022 |
Study information
| Verified date |
January 2024 |
| Source |
St. Anna Kinderkrebsforschung |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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-
and/or post-transplant MRD could induce MRD-negativity in patients who were MRD-positive
before and/or 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 mcg/m2/day 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 PCR/FLOW-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.
Description:
6.2.1 Screening / Pretreatment* The screening process begins on the date the subject (or
legally acceptable representative) signs the IRB/EC 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 inclusion/exclusion 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 6.2.2.
The following assessments/procedures 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 inclusion/exclusion 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 6.2.2 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 aspirate/biopsy taken within 14 days of the planned
treatment start of Blincyto can be used to determine eligibility.
6.2.3 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 aspirate/biopsy (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 and/or 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 6.2.4 Safety Follow-up Visit(s) / 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 6.2.5 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:
- Disease/Survival status
- Bone marrow aspirate/biopsy (morphological and MRD assessment) at day +180 post HSCT and
day 360 post HSCT.
- Hematology (neutrophils and platelets) 6.2.6 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.
6.2.7 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:
- Cytomorphology/percentage 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.
6.2.8 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 investigator's 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
