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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

Phase 2
18 Years
Open (Enrolling)
Acute Lymphoblastic Leukemia

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Trial Information

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

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).

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

MRD response rate defined by the incidence of MRD negativity

Outcome Time Frame:

within 24 weeks

Safety Issue:


Principal Investigator

Ralf Bargou, Professor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Julius-Maximilians-Universität Würzburg


Germany: Paul-Ehrlich-Institut

Study ID:




Start Date:

October 2007

Completion Date:

December 2014

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Minimal Residual Disease
  • adult ALL
  • immunotherapeutic treatment
  • anti-CD19 bispecific antibody derivative
  • Blinatumomab
  • MT103
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Neoplasm, Residual