Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoproliferative Disorders

Lymphatic Diseases

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Immunoproliferative Disorders

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Bispecific

Immunoglobulins

Blinatumomab

Participants received blinatumomab 15 μg/m²/day as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.

Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, followed by 15 μg/m²/day starting from Week 2 of treatment.

Participants received blinatumomab by continuous intravenous infusion over 4 weeks followed by a treatment-free interval of 2 weeks for up to 5 consecutive cycles. The initial dose was 5 μg/m²/day for the first seven days of treatment, a dose of 15 μg/m²/day in the subsequent 7 days, followed by 30 μg/m²/day starting from Week 3 of treatment.

Continuous intravenous infusion over four weeks per treatment cycle

Max Topp, MD

The purpose of this study is to determine whether the bispecific T-cell engager blinatumomab is effective, safe and tolerable in the treatment of patients with relapsed/refractory B-precursor ALL.

Relapsed/refractory B-precursor ALL in adult patients is an aggressive malignant disease with dismal prognosis and unmet medical need. Additional therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. The purpose of this study is to investigate the efficacy, safety and tolerability of different doses of the bispecific T-cell engager blinatumomab in adult patients with relapsed/refractory B-precursor ALL. Patrticipants will receive up to five 4-week cycles of intravenous blinatumomab treatment.

Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

An Open Label, Multicenter, Exploratory Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of the BiTE® Antibody Blinatumomab in Adult Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL)

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Hematological remissions were defined by the following criteria:

Complete Response/Remission (CR):

* Less than or equal to 5% blasts in the bone marrow
* No evidence of circulating blasts or extramedullar disease
* Full recovery of peripheral blood counts:

  * Platelets \> 100,000/μL
  * Hemoglobin ≥ 11 g/dL
  * Absolute neutrophil count (ANC) \> 1,500/μL

Complete Remission with only Partial Hematological Recovery (CRh\*):

* Less than or equal to 5% blasts in the bone marrow
* No evidence of circulating blasts or extramedullar disease
* Partial recovery of peripheral blood counts:

  * Platelets \> 50,000/μL
  * Hemoglobin ≥ 7 g/dL
  * ANC \> 500/μL.

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Complete Response/Remission (CR) was defined by the following criteria:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of circulating blasts or extramedullar disease
* Full recovery of peripheral blood counts:

  * Platelets \> 100,000/μL
  * Hemoglobin ≥ 11 g/dL
  * Absolute neutrophil count (ANC) \> 1,500/μL

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Complete remission with only partial hematological recovery (CRh\*) was defined by the following criteria:

* Less than or equal to 5% blasts in the bone marrow
* No evidence of circulating blasts or extramedullar disease
* Partial recovery of peripheral blood counts:

  * Platelets \> 50,000/μL
  * Hemoglobin ≥ 7 g/dL
  * ANC \> 500/μL.

At the end of each infusion period, a bone marrow aspiration/biopsy was performed to evaluate the efficacy of blinatumomab. All hematological assessments of bone marrow were reviewed in a central reference laboratory. Partial remission was defined by the following criteria:

• Bone marrow blasts ≤ 25%

A minimal residual disease (MRD) response is defined as MRD \< 10\^-4 blasts/nucleated cells based on polymerase chain reaction (PCR) evaluation of individual rearrangements of immunoglobulin or T cell receptor genes.

The percentage of participants who underwent immediate allogeneic HSCT (defined as those in remission who undergo HSCT without receiving any other treatments) after having discontinued or completed the core study.

Time to hematological relapse was measured for participants who achieved a CR or CRh\* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to disease progression. Participants without a documented relapse (hematological or extramedullary) and who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Participants who died without having reported hematological relapse or without showing any clinical sign of disease progression were censored on their day of death.

Hematological Relapse was defined as:

* Proportion of blasts in bone marrow \> 5%
* Extramedullary relapse.

Time to hematological relapse was analyzed by Kaplan-Meier methods.

Relapse-free survival was measured only for participants who achieved a CR or CRh\* during the core study and was measured from the time the participant first achieved remission until first documented relapse or death due to any cause. Participants without a documented relapse (hematological or extramedullary) or who did not die were censored at the time of their last bone marrow assessment or their last survival follow-up visit confirming remission. Relapse-free survival was estimated using Kaplan-Meier methods.

Overall survival was measured for all participants from the date of first infusion of blinatumomab until the date of death due to any cause. Participants who did not die were censored on the last documented visit date. Overall survival was estimated using Kaplan-Meier methods.

Adverse events were evaluated for severity according to the grading scale provided in the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 and according to the following:

Grade I (mild); Grade 2 (moderate); Grade 3 (severe - significantly limits the patient's ability to perform routine activities despite symptomatic therapy; Grade 4 (life-threatening); Grade 5 (death).

The investigator used medical judgment to determine if there was a causal relationship (ie, certain, probable, possible, unlikely, not related) between an adverse event and blinatumomab.

A serious adverse event is any untoward medical occurrence or effect, that at any dose:

resulted in death, was life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability or incapacity, is a congenital anomaly or birth defect or is a medically important condition.

The steady state concentration of blinatumomab was summarized as the observed concentrations collected at least 10 hours after the intravenous infusion was started for cycle 1 and cycle 2, respectively. Actual doses administered were used in the analysis.

Concentrations below the limit of detection (3 pg/mL) were set to zero before data analysis and concentrations below the lower limit of quantitation (50 pg/mL) were excluded from analysis.

Clearance was calculated as R0/Css; where R0 is the infusion rate (μg/m\^2/hr) and Css is the steady state concentration.

The activation of immune effector cells was monitored by the measurement of peripheral blood cytokine levels including interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon gamma (IFN-γ) using multiplex cytometric bead assays. The lower limit of quantification (LLOQ) is 125 pg/mL and the limit of detection (LOD) is 20 pg/mL.

Amgen Research (Munich) GmbH

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Blinatumomab 15 μg

Blinatumomab 5/15 μg

Blinatumomab 5/15/30 μg

All participants who received blinatumomab by continuous intravenous infusion during the core study.

Blinatumomab Overall

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Number of Prior Relapses

Primary Refractory

Relapsed

Relapsed / refractory Status

Yes, Sibling

Yes, Unrelated

Yes, Haploidentical (mother/father)

No prior allogeneic HSCT

Prior Allogeneic Hematopoietic Stem cell Transplantation (HSCT)

Study Director

Participants received blinatumomab as a continuous intravenous infusion at a constant flow rate over 4 weeks followed by a 2-week treatment-free interval for up to 5 consecutive cycles.

Full analysis set (FAS), defined as participants who received any infusion of the assigned study medication, who completed at least the first treatment cycle and for whom at least one response assessment was available after the start of treatment.

Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

ABlinatumomab 5/15/30 μg

Percentage of Participants With a Best Response of Complete Remission Within 2 Cycles of Treatment

Percentage of Participants With a Best Response of Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment

Percentage of Participants With a Best Response of Partial Remission Within 2 Cycles of Treatment

Percentage of Participants With a Minimal Residual Disease (MRD) Response During the Core Study

Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab

Blinatumimab Overall

Participants who reached complete remission or complete remission with partial hematological recovery during the core study.

Time to Hematological Relapse

Relapse-free Survival

Overall Survival

Any adverse event (AE)

Adverse events of at least CTC grade 3

Treatment-related adverse events

Related adverse events of at least CTC grade 3

Serious adverse events

Serious adverse events of at least CTC grade 3

Serious related adverse events

AEs leading to interruption of blinatumomab

AEs leading to discontinuation of blinatumomab

AEs leading to death

Safety analysis set, defined as all participants who received any infusion of blinatumomab.

Number of Participants With Treatment-emergent Adverse Events

Participants receiving blinatumomab 5 μg/m²/day.

Blinatumomab 5 μg

Participants receiving blinatumomab 15 μg/m²/day.

Participants receiving blinatumomab 30 μg/m²/day.

Blinatumomab 30 μg

Participants who received blinatumomab and who had available pharmacokinetic data.

Steady State Blinatumomab Concentration

All participants who received blinatumomab.

Clearance of Blinatumomab

IL-6: Cycle 1 (N=35)

IL-6: Cycle 2 (N=22)

IL-6: Cycle 3 (N=11)

IL-10: Cycle 1 (N=35)

IL-10: Cycle 2 (N=22)

IL-10: Cycle 3 (N=11)

IFN-Ɣ: Cycle 1 (N=35)

IFN-Ɣ: Cycle 2 (N=22)

IFN-Ɣ: Cycle 3 (N=11)

IL-2: Cycle 1 (N=35)

IL-2: Cycle 2 (N=22)

IL-2: Cycle 3 (N=11)

TNF-α: Cycle 1 (N=35)

TNF-α: Cycle 2 (N=22)

TNF-α: Cycle 3 (N=11)

Participants who received blinatumomab and who had evaluable pharmacodynamic data.

Spots Global Cancer Trial Database for Study of the BiTE® Blinatumomab (MT103) in Adult Patients With Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia (ALL)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial