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
- Conditions
- Adult patients with relapsed / refractory B-precursor ALL.MedDRA version: 19.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-002257-61-DE
- Lead Sponsor
- Amgen Research (Munich) GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 220
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 <br>- To evaluate pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab<br>- To evaluate CNS symptoms and explore potential predictive factors for CNS events associated with blinatumomab;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.;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. <br>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
- Secondary Outcome Measures
Name Time Method