Clinical phase II study to evaluate the efficacy and safety of the bispecific antibody blinatumomab (MT103) in adult patients with acute lymphoblastic leukemia (ALL) that did not respond to previous therapy or that relapsed after initially successful previous therapy

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2011-002257-61-DE
• Date of registration: 01/08/2011
• Prospective Registration: Yes
• Primary sponsor: Amgen Research (Munich) GmbH
• Public title: Clinical phase II study to evaluate the efficacy and safety of the bispecific antibody blinatumomab (MT103) in adult patients with acute lymphoblastic leukemia (ALL) that did not respond to previous therapy or that relapsed after initially successful previous therapy
• Scientific title: An open label, multicenter, phase II study to evaluate efficacy and safety of the BiTE antibody blinatumomab in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL)
• Date of first enrolment: 15/11/2011
• Target sample size: 220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002257-61
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

• Name: IHQ medical Info-Clinical Trials
• Affiliation: Amgen (EUROPE) GmbH

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with Ph-negative B-precursor ALL, with any of the following:
- relapsed or refractory with first remission duration less than or equal to 12 months in first salvage or
- relapsed or refractory after first salvage therapy or
- relapsed or refractory within 12 months of allogeneic HSCT
2. 10% or more blasts in bone marrow
3. In case of clinical signs of additional extramedullary disease: measurable disease (at least one lesion = 1.5 cm)
4. Eastern Cooperative Oncology Group (ECOG) performance status = 2
5. Age = 18 years
6. Ability to understand and willingness to sign a written informed consent
7. Signed and dated written informed consent is available

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 176
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

Exclusion criteria:
1. Patients with Ph-positive ALL
2. Patients with Burkitt´s Leukemia according to WHO classification
3. History or presence of clinically relevant CNS pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis
4. Active ALL in the CNS or testes
5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
6. Autologous HSCT within six weeks prior to start of blinatumomab treatment
7. Allogeneic HSCT within three months prior to start of blinatumomab treatment
8. Any active acute Graft-versus-Host Disease (GvHD), or active chronic GvHD Grade 2 – 4
9. Any systemic therapy against GvHD within two weeks prior to start of blinatumomab treatment
10. Cancer chemotherapy within two weeks prior to start of blinatumomab treatment (intrathecal chemotherapy and dexamethasone are allowed until start of blinatumomab treatment)
11. Radiotherapy within two weeks prior to start of blinatumomab treatment
12. Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment
13. Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment
14. Treatment with any other investigational medicinal product (IMP) after signature of informed consent
15. Eligibility for allogeneic HSCT at the time of enrollment (as defined by disease status, performance status and availability of donor)
16. Known hypersensitivity to immunoglobulins or to any other component of the IMP formulation
17. Abnormal laboratory values as defined below:
a. AST (SGOT) and/or ALT (SGPT) and/or AP = 5 x upper limit of normal (ULN)
b. Total bilirubin = 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease)
c. Creatinine = 1.5 ULN or Creatinine clearance < 50 ml/min (calculated)
d. Hemoglobin (Hb) = 9 g/dl (transfusion allowed)
18. History of malignancy other than ALL within five years prior to start of blinatumomab treatment with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix
19. Active uncontrolled infection, any other concurrent disease or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator
20. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
21. Pregnant or nursing women
22. Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Male patients not willing to ensure not to beget a child during participation in the study and at least three months thereafter
23. Previous treatment with blinatumomab



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Adult patients with relapsed / refractory B-precursor ALL.
MedDRA version: 19.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Blinatumomab
Product Code: MT103, AMG103
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Blinatumomab
CAS Number: 853426-35-4
Current Sponsor code: MT103
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 30.3 (clinical)-38.5 (commercial)

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: At screening and at the end of each treatment cycle a bone marrow aspiration/biopsy will be performed to evaluate the efficacy of blinatumomab.
Following the last treatment cycle, there will be efficacy follow-up visits at three, six, nine, 12, 18 and 24 months after treatment start for patients who did not undergo allogeneic HSCT

Primary end point(s): CR (Complete response/remission) + CRh* (Complete response/remission with partial recovery of peripheral blood counts) rate within two cycles of treatment with blinatumomab.

Main Objective: To evaluate efficacy of blinatumomab in patients with relapsed/refractory B-precursor ALL.

Secondary Objective: - To evaluate safety of blinatumomab in patients with relapsed/refractory B-precursor ALL
- To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab
- To evaluate CNS symptoms and explore potential predictive factors for CNS events associated with blinatumomab

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Assessment at the end of each treatment cycle (and optionally at day 15 of the first cycle) and during efficacy follow up (until 24 months after treatment start at most)
2. Until patient´s last follow up (until 3 years after treatment start at most)
3.-5. At the end of the first and second treatment cycle and optionally at day 15 of the first cycle
6.-8. Throughout entire study, until three years after treatment start at most
9. 100 days after HSCT, if applicable
10.-11. At baseline and during the first two treatment cycles

Exploratory endpoints
1.-2. At the end of each treatment cycle (and optionally at day 15 of the first cycle)
3. At baseline, during the first two treatment cycles, and during efficacy follow-up (2 years after treatment start at most)
4. Stage 4 of study

Secondary end point(s): 1. Time to hematological relapse (duration of response)
2. Proportion of patients eligible for allogeneic HSCT who undergo the procedure after treatment with blinatumomab
3. CR rate within two cycles of treatment with blinatumomab
4. CRh* rate within two cycles of treatment with blinatumomab
5. PR rate within two cycles of treatment with blinatumomab
6. Relapse-free survival
7. Event-free survival
8. Overall survival
9. Overall incidence and severity of AEs
10. 100-day mortality after allogeneic HSCT
11. Pharmacokinetic parameters: steady state concentration of blinatumomab
12. Serum cytokine concentrations

Exploratory endpoints
1. Rate of MRD response within two cycles of treatment with blinatumomab
2. Rate of MRD complete response within two cycles of treatment with blinatumomab
3. Quantification and characterization of peripheral blood lymphocyte subsets
4. Neurological exam abnormalities and changes from baseline

Secondary ID(s)

MT103-211

Source(s) of Monetary Support

Amgen Research (Munich) GmbH