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Clinical Phase 2 Study to evaluate the efficacy of the bispecific antibody blinatumomab in adult subjects with Philadelphia Positive Acute Lymphoblastic Leukemia (PH+ ALL) that did not respond to previous therapy or that relapsed after initially successful previous therapy.

Phase 1
Conditions
Adult patients with relapsed and/or refractory Philadelphia Chromosome- positive B-precursor ALL
MedDRA version: 19.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
MedDRA version: 19.0Level: LLTClassification code 10063625Term: Acute lymphoblastic leukemia recurrentSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2013-000706-36-GB
Lead Sponsor
Amgen Inc.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
45
Inclusion Criteria

1. Patients with Ph+ B-precursor ALL, with any of the following:
• Relapsed or refractory to at least one second generation TKI (dasatinib, nilotinib, bosutinib, ponatinib)
OR intolerant to second generation TKI and intolerant or refractory to imatinib mesylate
2. Greater than 5% blasts in bone marrow
3. Eastern Cooperative Oncology Group (ECOG) performance status = 2
4. Age = 18 years of age, at the time of informed consent
5. Subject has provided informed consent or subject’s legally acceptable representative has provided informed consent when the subject has any kind of condition that, in the opinion of the Investigator, may compromise the ability of the subject to give written informed consent.
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 28
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

1. History of malignancy other than ALL within 5 years prior to start of protocol-required therapy with the exception of:
- Malignancy treated with curative intent and with no known active disease present for 5 years before enrollment and felt to be at low risk for recurrence by the treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Adequately treated breast ductal carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
2. History or presence of clinically relevant CNS pathology as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis
- With the exception of CNS leukemia that is well controlled with intrathecal therapy
3. Active ALL in the CNS (confirmed by CSF analysis) or testes (no clinical sign thereof)
4. Isolated extramedullary disease
5. Current autoimmune disease or history of autoimmune disease with potential CNS involvement
6. Allogeneic HSCT within 12 weeks prior to start of blinatumomab
7. Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade 4 according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment
8. Any systemic therapy against GvHD within 2 weeks prior to start of blinatumomab
9. Cancer chemotherapy within 2 weeks prior to start of blinatumomab (exceptions: prior TKI therapy is allowed but must be completed prior to start of blinatumomab; prophylactic intrathecal chemotherapy and prephase dexamethasone are allowed until start of blinatumomab). In addition, any subject whose organ toxicity (excluding hematologic) from prior ALL treatment has not resolved to no more than CTCAE grade 1.
10. Immunotherapy (eg, rituximab) within 4 weeks prior to start of blinatumomab
11. Subject received prior anti-CD19 therapy
12. Eligibility for alloHSCT at the time of enrollment (as defined by disease status, performance status and availability of donor)
13. Abnormal screening laboratory values as defined below:
- AST (SGOT) and/or ALT (SGPT) and/or alkaline phosphatase = 5 x upper limit of normal (ULN)
- Total bilirubin = 1.5 x ULN (unless related to Gilbert´s or Meulengracht disease)
- Creatinine = 1.5 ULN or creatinine clearance < 60 mL/min (calculated)
14. Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive).
15. Subject is pregnant or breast feeding, or might become pregnant within 3 months after the last dose of protocol-specified therapy
16. Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving blinatumomab and for an additional 3 months after the last dose of protocol-specified therapy
17. Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception for at least an additional 3 months after the last dose of protocol-specified therapy
18. Male who has a pregnant partner, and is not willing to use a condom during sexual activity for 3 months after the last dose of protocol-specified therapy
19. Currently receiving treatment in another investigational device or drug study or less than 30 days s

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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