Overview

This trial is active, not recruiting.

Condition acute lymphoblastic leukemia
Treatment blinatumomab (mt103)
Phase phase 2
Sponsor Amgen Research (Munich) GmbH
Start date October 2007
End date December 2009
Trial size 21 participants
Trial identifier NCT00560794, MT103-202

Summary

The purpose of this study is to determine whether the bispecific T-cell engager (BiTE®) Blinatumomab (MT103) is effective in the treatment of ALL patients with minimal residual disease.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients will receive Blinatumomab (MT103) as continuous intravenous infusion at constant flow rate over 4 weeks followed by a 2 weeks treatment free period, defined as one treatment cycle (up to a maximum of 10 cycles)
blinatumomab (mt103) Blinatumomab
15µg/m2/24h,30µg/m2/24h, or 60µg/m2/24h continuous intravenous (CIV) over 4 weeks, up to 10 cycles or progression or unacceptable toxicity

Primary Outcomes

Measure
MRD response rate defined by the incidence of MRD negativity
time frame: within 24 weeks

Secondary Outcomes

Measure
Time to hematological relapse
time frame: until hematological relapse
Change in MRD level
time frame: until End of Study (EoS)
Time to molecular relapse
time frame: until molecular relapse
Incidence and severity of adverse events
time frame: until EoS
Quantification and characterization of peripheral blood lymphocytes
time frame: until EoS
Cytokine serum concentrations
time frame: until EoS
Pharmacokinetic parameters
time frame: until EoS

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - B-precursor ALL patients in complete hematological remission with molecular failure or molecular relapse starting at any time after consolidation I of front-line therapy within GMALL standards or at any time outside GMALL standards. - Patients must have a molecular marker for evaluation of minimal residual disease which is either Bcr/abl at any detection level or individual rearrangements of immunoglobulin or TCR-genes measured by an assay with a sensitivity of minimum 10-4: At least one individual marker at a quantitative level ³10-4. - ECOG Performance Status < 2 - Ability to understand and willingness to sign a written informed consent - Signed and dated written informed consent is available Exclusion Criteria: - Current extra medullar involvement - History of or current relevant CNS pathology (except migraine/headache and/or previous infiltration of cerebrospinal fluid (CSF) by ALL) - Current infiltration of cerebrospinal fluid by ALL - History of or current autoimmune disease - Autologous stem cell transplantation within 6 weeks prior to study entry - Any prior allogeneic stem cell transplantation - Cancer chemotherapy within 4 weeks prior to study treatment (except for intrathecal prophylaxis and/or low dose maintenance therapy such as vincalkaloids, mercaptopurine, methotrexate, steroids) - Radiotherapy within 4 weeks prior to study treatment - Therapy with monoclonal antibodies (Rituximab, MabCampath) within 6 weeks prior to study treatment - Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation - Presence of human anti-murine antibodies (HAMA) - Abnormal bone marrow, renal or hepatic function - Indication for a hypercoagulative state - History of malignancy other than ALL within 5 years prior to study entry, with the exception of basal cell carcinoma of the skin or cervix carcinoma in situ - Active severe infection, any other concurrent disease or medical condition that are deemed to interfere with the conduct of the study as judged by the investigator - Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HbsAg positive) or hepatitis C virus (anti-HCV positive - Pregnant or nursing women - Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception dur-ing participation in the study and at least three months thereafter

Additional Information

Official title Open-label, Multicenter Phase II Study to Investigate the Efficacy, Safety, and Tolerability of the Bispecific T-cell Engager (BiTE®) MT103 in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia
Principal investigator Ralf Bargou, Professor
Description The presence of leukemia cells below the cytological detection limit (5% leukemic cells) is defined as minimal residual disease (MRD). If no MRD is detectable (<10-4 =< 1 leukemia cell per 104 bone marrow cells) a complete molecular remission is reached. In the last years a series of retrospective studies has shown that MRD in adult ALL is an independent prognostic factor as already demonstrated for childhood leukemia. Diagnostic tools for MRD are polymerase chain reaction (PCR) and/or flow cytometry. PCR analysis can detect fusion transcripts such as bcr/abl and individual clonal rearrangements of immu-noglobulins (IgH) and/or T-cell receptor genes (TCR). About 25% of patients with MRD defined by rearrangement comprise a high-risk group with a 94% relapse rate within 3 years. In general for patients with MRD, who are not eligible for allogenic stem cell transplantation, curative treatment is not available. This accounts for MRD defined by the Philadelphia chromosome translocation as well as for MRD defined by rearrangement. The current study is set up to address the question of treating MRD positive ALL with the bispecific anti-CD19 x anti-CD3 antibody derivative Blinatumomab (MT103).
Trial information was received from ClinicalTrials.gov and was last updated in November 2012.
Information provided to ClinicalTrials.gov by Amgen Research (Munich) GmbH.