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-ES
• Date of registration: 03/10/2011
• Prospective Registration: Yes
• Primary sponsor: Micromet AG
• 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: 23/11/2011
• Target sample size: 61
• 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, Switzerland, United Kingdom, United States

Contacts

• Name: Clinical Development Department
• Affiliation: Micromet AG

• Name: Clinical Development Department
• Affiliation: Micromet AG

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 or
- if age 60 years or older: relapsed or refractory disease in first or later salvage independent of first remission duration
2. 10% or more blasts in bone marrow
3. In case of clinical signs of additional extramedullary disease: measurable disease (at least one lesion major or equal to 1.5 cm)
4. Eastern Cooperative Oncology Group (ECOG) performance status minor or equal to 2
5. Age major or equal to 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 46
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion criteria:
1. Patients with Ph-positive ALL
2. History or presence of clinically relevant CNS pathology as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, organic brain syndrome, psychosis
3. Active ALL in the CNS or testes
4. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
5. Autologous HSCT within six weeks prior to start of blinatumomab treatment
6. Allogeneic HSCT within three months prior to start of blinatumomab treatment
7. Any active acute Graft-versus-Host Disease (GvHD), or active chronic GvHD Grade 2 to 4
8. Immunosuppressive therapy against GvHD within two weeks prior to start of blinatumomab treatment
9. Cancer chemotherapy within two weeks prior to start of blinatumomab treatment (intrathecal prophylaxis and pre-phase with dexamethasone are allowed until start of blinatumomab treatment)
10. Radiotherapy within four weeks prior to start of blinatumomab treatment
11. Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treatment
12. Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment
13. Treatment with any other investigational medicinal product (IMP) after signature of informed consent
14. Known hypersensitivity to immunoglobulins or to any other component of the IMP formulation
15. Abnormal laboratory values as defined below:
a. AST (SGOT) and/or ALT (SGPT) and/or AP major or equal to 5 x upper limit of normal (ULN)
b. Total bilirubin major or equal to 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease)
c. Creatinine major or equal to 1.5 ULN or Creatinine clearance < 50 ml/min (calculated)
d. Hemoglobin (Hb) minor or equal to 9 g/dl (transfusion allowed)
16. Active malignancy requiring treatment other than ALL within two 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
17. 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
18. Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive)
19. Pregnant or nursing women
20. 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
21. Previous treatment with blinatumomab


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

Health Condition(s) or Problem(s) studied

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

Adult patients with relapsed / refractory B-precursor ALL.
MedDRA version: 14.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Product Name: Blinatumomab
Product Code: MT103
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: 33-

Primary Outcome(s)

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

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.

Secondary Objective: - To evaluate safety of blinatumomab in patients with relapsed/refractory B-precursor ALL
- To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab

Secondary Outcome(s)

Secondary end point(s): 1. Duration of CR and CRh*
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. Overall survival
8. Overall incidence and severity of AEs
9. 100-day mortality after allogeneic HSCT
10. Pharmacokinetic parameters: steady state concentration of blinatumomab
11. 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

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)

Secondary ID(s)

2011-002257-61-DE

MT103-211

Source(s) of Monetary Support

Micromet AG