Clinical Study With Blinatumomab in Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)
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Purpose
The purpose of this study is to confirm whether the bispecific T cell engager antibody blinatumomab (MT103) is effective and safe in the treatment of patients with relapsed or refractory Acute Lymphoblastic Leukemia (ALL).
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Lymphoblastic Leukemia |
Drug: Blinatumomab |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | An Open Label, Multicenter, Phase II Study to Evaluate Efficacy and Safety of the BiTE Antibody Blinatumomab in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) |
- CR + CRh* rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]rate of complete remission and complete remission with partial hematologic recovery within in the first two treatment cycles
- Proportion of patients eligible for allogeneic hematopoietic stem cell transplantation (HSCT) who undergo the procedure after treatment with blinatumomab [ Time Frame: within 17 months ] [ Designated as safety issue: No ]
- CR rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- CRh* rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- Partial remission (PR) rate [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- Relapse-free survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Number of AEs per patient [ Time Frame: up to 8 months ] [ Designated as safety issue: Yes ]
- 100-day mortality after allogeneic HSCT [ Time Frame: within 4 years ] [ Designated as safety issue: Yes ]
- Steady state concentration of blinatumomab (pharmacokinetics) [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- Serum cytokine concentrations [ Time Frame: up to 2 years ] [ Designated as safety issue: Yes ]
- Rate of MRD response [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- Rate of MRD complete response [ Time Frame: within 10 weeks ] [ Designated as safety issue: No ]
- Time to hematological relapse [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Event-free survival [ Time Frame: up to 4 years ] [ Designated as safety issue: No ]
- Concentration of peripheral blood lymphocyte subsets [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 180 |
| Study Start Date: | November 2011 |
| Estimated Study Completion Date: | June 2017 |
| Estimated Primary Completion Date: | September 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Blinatumomab
Bispecific T cell engager antibody
|
Drug: Blinatumomab
continuous intravenous infusion over four weeks per treatment cycle
Other Names:
|
Detailed Description:
Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prog-nosis. Several studies have reported long term survival to be below 10%. Major prognostic factors are duration of first complete remission (CR1) and age. With current salvage chemotherapy, complete remission (CR) rate is low (20 to 30%) in patients in first salvage with short duration (< one year) of first remission, patients relapsed after first salvage, or patients aged 60 years and older. Duration of CR is usually very short (median disease free survival [DFS]: 2.0-7.5 months). Allogeneic hematopoietic stem cell transplantation (HSCT) may provide a curative treatment option for patients in CR with a satisfactory donor and appropriate clinical status including age, organ function, and remission status. Allogeneic HSCT is not an option in most elderly patients with relapsed ALL. Additional therapeutic approaches are urgently needed.
Blinatumomab (also termed MT 103) is a bispecific single-chain antibody derivative against CD (cluster of differentiation)19 and CD3, designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. In vitro data indicate CD19+ lymphoma and leukemia cell lines to be extremely sensitive to blinatumomab-mediated cytotoxicity.Blinatumomab has the potential to provide meaningful therapeutic benefits to patients compared with existing treatments for this patient population.
The purpose of this study is to confirm whether the bispecific T-cell engager blinatumomab (MT103) is effective and safe in the treatment of patients with relapsed or refractory ALL. Patients will receive up to five 4-week cycles of intravenous blinatumomab treatment.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
- 10% or more blasts in bone marrow
- In case of clinical signs of additional extramedullary disease: measurable disease
- ECOG performance status ≤ 2
- Age ≥ 18 years
Exclusion Criteria:
- Patients with Ph-positive ALL
- Patients with Burkitt's Leukemia according to WHO classification
- History or presence of clinically relevant CNS pathology
- Active ALL in the CNS or testes
- Current autoimmune disease or history of autoimmune disease with potential CNS involvement
- Autologous HSCT within six weeks prior to start of blinatumomab treatment
- Allogeneic HSCT within three months prior to start of blinatumomab treatment
- Any active acute GvHD, or active chronic GvHD Grade 2 - 4
- Any systemic therapy against GvHD within two weeks prior to start of blinatumomab treatment
- Cancer chemotherapy within two weeks prior to start of blinatumomab treatment
- Radiotherapy within two weeks prior to start of blinatumomab treatment
- Immunotherapy (e.g., rituximab) within four weeks prior to start of blinatumomab treat-ment
- Any investigational anti-leukemic product within four weeks prior to start of blinatumomab treatment
- Treatment with any other IMP after signature of informed consent
- Eligibility for allogeneic HSCT at the time of enrollment
- Known hypersensitivity to immunoglobulins or to any other component of the IMP formulation
- Abnormal laboratory values indicative of inadequate renal or liver function
- History of malignancy requiring treatment 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
- Any concurrent disease or medical condition that is deemed to interfere with the conduct of the study
- Infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
- Pregnant or nursing women
- Women of childbearing potential not willing to use an effective form of contraception. Male patients not willing to ensure not to beget a child
- Previous treatment with blinatumomab
Contacts and Locations| Contact: Henry Adewoye, MD | +1805441864 | hadewoye@amgen.com |
| Contact: Birgit Huber, PhD | +49 - 89 - 89 5277 ext 347 | bhuber@amgen.com |
Show 39 Study Locations| Principal Investigator: | Nicola Gökbuget, MD | Klinikum der Goethe Universität Frankfurt |
| Principal Investigator: | Max Topp, MD | Julius-Maximilians-Universität, Medizinische Klinik und Poliklinik II, Würzburg |
| Principal Investigator: | Hagop Kantarjian, MD | MD Anderson Cancer Center, Houston, Texas |
More Information
No publications provided
| Responsible Party: | Amgen Research (Munich) GmbH |
| ClinicalTrials.gov Identifier: | NCT01466179 History of Changes |
| Other Study ID Numbers: | MT103-211, 2011-002257-61 |
| Study First Received: | October 28, 2011 |
| Last Updated: | April 10, 2013 |
| Health Authority: | United States: Food and Drug Administration Germany: Paul-Ehrlich-Institut France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Italy: Ethics Committee Spain: Agencia Española de Medicamentos y Productos Sanitarios United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Amgen Research (Munich) GmbH:
|
B-ALL relapsed ALL refractory ALL adult ALL Leukemia Leukemia, Lymphoid precursor cell lymphoblastic leukemia-lymphoma |
Lymphatic diseases Lymphoproliferative disorders bispecific antibody anti-CD19 Immunotherapeutic treatment immunoproliferative disorders |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases Antibodies Antibodies, Bispecific Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 21, 2013