Primary objective(s)• To evaluate the efficacy of blinatumomab to induce complete MRD responseKey secondary objective for patients with Ph-negative ALL • To evaluate the effect of blinatumomab on hematological relapseOther Secondary objectives• To…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study endpoints
Primary endpoint
• Proportion of patients who achieve complete MRD response defined by absence
of MRD after one cy-cle of treatment with blinatumomab
Key secondary endpoint in patients with Ph-negative ALL
• Hematological relapse-free survival rate at 18 months following initiation of
blinatumomab
Secondary outcome
Secondary endpoints
• Overall Survival
• Mortality rate within 100 days after allogeneic HSCT
• Time to hematological relapse
• Duration of complete MRD response
• Effect on MRD level
• Overall incidence and severity of adverse events
• Patient*s quality of life during and after therapy
• Resource utilization
Background summary
Study rationale
The detection of minimal residual disease (MRD) after induction therapy and/or
consolidation therapy is an inde-pendent prognostic factor for poor outcome of
adult ALL. No standard treatments are available for patients with MRD-positive
B-precursor ALL. Blinatumomab (MT103) is a bispecific single-chain antibody
construct designed to link B cells and T cells resulting in T-cell activation
and a cytotoxic T-cell response against CD19 expressing cells. In vitro and ex
vivo data indicate CD19 positive lymphoma and leukemia cell lines to be
extremely sensitive to blinatumomab mediated cytotoxicity.
The recent Phase II clinical study MT103-202 treated adult patients with
B-precursor ALL with persistent or recur-rent MRD with up to 7 cycles of a
4-week treatment course of blinatumomab at a dose of 15µg/m²/day. A com-plete
MRD response was seen in 16 out of 20 evaluable patients. The majority of the
patients remained in hema-tological CR up to 15+ months without any further
treatment.
Blinatumomab has also been administered in 3 pediatric patients with ALL at a
dose of 15µg/m²/day as *named patient use*. These patients had relapsed ALL
without further treatment option. All three patients showed com-plete MRD
response to blinatumomab. After end of treatment with blinatumomab one patient
has relapsed, the other two patients are in ongoing remission.
This study is designed to confirm the efficacy, safety, and tolerability of
blinatumomab in patients with MRD of B precursor ALL in complete hematological
remission.
Study objective
Primary objective(s)
• To evaluate the efficacy of blinatumomab to induce complete MRD response
Key secondary objective for patients with Ph-negative ALL
• To evaluate the effect of blinatumomab on hematological relapse
Other Secondary objectives
• To evaluate overall survival in patients with ALL treated with blinatumomab
• To evaluate the effect of blinatumomab on the 100d mortality rate associated
with allogeneic HSCT
• To evaluate the safety and tolerability of blinatumomab
• To evaluate the effect of blinatumomab on duration of MRD negativity
• To evaluate the effect of blinatumomab on the kinetics of MRD
• To evaluate patient*s quality of life during and after therapy
• To evaluate resource utilization
Exploratory objectives
• To assess potential biologic predictors of response to blinatumomab
Study design
Study design
Confirmatory multicenter, single-arm study to assess the efficacy, safety and
tolerability of blinatumomab in pa-tients with MRD-positive B-precursor ALL.
All enrolled patients will be statistically evaluated for the primary endpoint
complete MRD response rate.
The key secondary endpoint of *hematological relapse-free survival rate at 18
months* - will be assessed in at least 50 patients with Ph-negative B-precursor
ALL, not having undergone allogeneic HSCT during the 18-month observation
period.
Intervention
4 cycles of continue infusion. One cyle consists of of 4 weeks of 15 µg/m2/d
Blinatumomab and after that 2 weeks rest for the treatment of patients with
minimal residual disease of B-precursor acute lymfoblastic leukemia.
Study burden and risks
A central vene catheter is needed for the continous IV infusion. This means
that there is a risk for infection at the injection spot, inside the cathether
or at the tip of the catheter. A coagulated mass can be formed. Nevertheless,
these catheters are standardly usd in the treatment of leukemia and not just
only in this trial.
Taking bloodsamples can cause faint, illness or onconfortable feelings or
hematogenesis. In rare cases trombosis appears or an infection at the spot
where the bloodsample has been taken. When the bloodpressure is being taken,
hematogenesis can appear on the arm as the manchet can be too tight.
Staffelseestr. 2
Munich 81477
DE
Staffelseestr. 2
Munich 81477
DE
Listed location countries
Age
Inclusion criteria
1. Patients with B-precursor ALL in complete hematological remission defined as less than 5% blasts in bone marrow after at least three intense chemotherapy blocks (e.g., GMALL induction I-II/consolidation I, induc-tion/intensification/consolidation or three blocks of Hyper CVAD)
2. Presence of minimal residual disease at a level of >=10-3 (molecular failure or molecular relapse) in an assay with a minimum sensitivity of 10-4 documented after an interval of at least 2 weeks from last systemic chemotherapy
3. For evaluation of minimal residual disease, patients must have at least one molecular marker based on indi-vidual rearrangements of immunoglobulin or TCR-genes or a flow cytometric marker profile, evaluated by a national or local reference lab approved by the sponsor
4. Bone marrow specimen or peripheral blood from primary diagnosis (a sufficient amount of DNA (30µg) or a respective amount of cell material) for clone-specific MRD assessment must be received by central MRD lab and lab must con-firm that the sample is available
5. Bone marrow function as defined in the protocol
6.Renal and hepatic function as defined in the protocol
7. Negative HIV test, negative hepatitis B (HbsAg) and hepatitis C virus (anti-HCV) test.
8. Negative pregnancy test in women of childbearing potential.
9. ECOG Performance Status 0 or 1
10. equal or older 18 years
11. Ability to understand and willingness to sign a written informed consent
12. Signed and dated written informed consent is available
Exclusion criteria
1. Presence of circulating blasts or current extra-medullary involvement by ALL
2. History of relevant CNS pathology or current relevant CNS pathology (e.g. seizure, paresis, aphasia, cere-brovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson*s disease, cerebellar disease, organic brain syndrome, psychosis, coordination or movement disorder)
3. Current infiltration of cerebro-spinal fluid by ALL
4. History of or active relevant autoimmune disease
5. Prior allogeneic HSCT
6. Eligibility for treatment with TKIs (i.e., Philadelphia chromosome-positive (Ph) patients with no documented treatment failure of or intolerance/contraindication to at least 2 TKIs)
7. Systemic cancer chemotherapy within 2 weeks prior to study treatment, (except for intrathecal prophylaxis)
8. Radiotherapy within 4 weeks prior to study treatment
9. Autologous hematopoietic stem cell transplantation (HSCT) within six weeks prior to study treatment
10. Therapy with monoclonal antibodies (rituximab, alemtuzumab) within 4 weeks prior to study treatment
11. Treatment with any investigational product within four weeks prior to study treatment
12. Previous treatment with blinatumomab
13. Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation
14. Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix
15. Active infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator
16. Nursing women or women of childbearing potential not willing to use an effective form of contraception dur-ing participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-018314-75-NL |
| ClinicalTrials.gov | NCT01207388 |
| CCMO | NL37170.078.11 |