Phase II Study of the BiTE® Blinatumomab (MT103) in Patients With Minimal Residual Disease of B-precursor Acute Lymphoblastic Leukemia (ALL)

Amgen Research (Munich) GmbH21 enrolled

Overview

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.

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 = less than 1 leukemia cell per 10\^4 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 immunoglobulins (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-cluster of differentiation (CD)19 x anti-CD3 antibody derivative blinatumomab (MT103).

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Lymphoblastic Leukemia

Interventions

Blinatumomab (MT103)BIOLOGICAL

Administered by continuous intravenous (CIV) over 4 weeks per cycle

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 German Multicenter Study Group on Adult Acute Lymphoblastic Leukemia (GMALL) standards or at any time outside GMALL standards. * Patients must have a molecular marker for evaluation of minimal residual disease which is either Breakpoint cluster region/gene on human chromosome #9 (Bcr/abl) at any detection level or individual rearrangements of immunoglobulin or T-cell receptor (TCR)-genes measured by an assay with a sensitivity of minimum 10\^-4: At least one individual marker at a quantitative level ≥ 10\^-4. * Eastern Cooperative Oncology Group (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 central nervous system (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 vinca alkaloids, 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 during participation in the study and at least three months thereafter

Locations (6)

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, Germany

Julius-Maximilians-Universität Würzburg

Würzburg, Bavaria, Germany

Klinikum der J.W. Goethe Universität

Frankfurt am Main, Hesse, Germany

Universitätsklinikum Münster

Münster, North Rhine-Westphalia, Germany

Outcomes

Primary Outcomes

Percentage of Participants With a Minimal Residual Disease (MRD) Response Within 4 Cycles of Treatment

MRD Response is defined as: * If Philadelphia Chromosome (Ph) positive (+) or translocation (t) (4;11), response was achieved when Ph or t(4;11) was below detection limit and individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4. * If Ph and t(4;11) negative, response was achieved when individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4.

Time frame: Within 4 treatment cycles, 24 weeks

Secondary Outcomes

Percentage of Participants With an MRD Response After Each Treatment Cycle

MRD Response is defined as: * If Philadelphia Chromosome (Ph)+ or t(4;11), response was achieved when Ph or t(4;11) was below detection limit and individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4. * If Ph and t(4;11) negative, response was achieved when individual rearrangements of immunoglobulin or T-cell receptor genes are below 10\^-4.

Time frame: At the end of each treatment cycle - Weeks 4, 10, 16, and 22.

Time to Hematological Relapse

The time to hematological relapse is defined as the time between start of first infusion of blinatumomab and the first result of hematological relapse. Participants without an event of hematological relapse were censored on their last available date of bone marrow aspiration/biopsy. Hematological relapse is defined as \> 5% leukemia cells in bone marrow. Time to hematological relapse was analyzed using Kaplan-Meier methods.

Time frame: Up to the data cut-off date of 14 January 2010; maximum duration of follow-up was 564 days.

Time to MRD Progression

Time to MRD progression is defined for participants who do not show MRD response at any time during the study as the time from start of first infusion until the first result of MRD progression or hematological relapse, if no MRD progression was diagnosed before hematological relapse. For participants who showed MRD response during the study the time to MRD progression is defined as the time from the date of the first MRD response to the date of MRD relapse. Participants without an event of MRD progression were censored on the day of their last bone marrow aspiration/biopsy. Participants who received a bone marrow transplant were censored on the last day of bone marrow aspiration/biopsy before transplantation. MRD progression is defined as the increase in the MRD level by 1 log as compared to the baseline level (equal to a 10-fold increase in the number of MRD cells), and had to be confirmed within 6 weeks.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.