Neoplasms

Blood and Lymph Conditions

All Conditions

Hematologic Neoplasms

Hematologic Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

MEDI-551 will be administered by intravenous infusion at dose of 2, 4 or 8 mg/kg once per week on Days 1 and 8 in the first cycle and then once every 28 days at the start of each subsequent cycle

MEDI-551

The primary objective of this study is to evaluate the safety and tolerability of MEDI-551 in Japanese patients with relapsed or refractory advanced B-cell malignancies.

A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

A Phase 1, Dose-escalation Study of MEDI-551, a Humanized Monoclonal Antibody Directed Against CD19, in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

A MEDI-551 treatment-related AE of any toxicity grade that lead to an inability to receive a full cycle (2 doses) of MEDI-551, or, any Grade 3 or higher toxicity that could not be reasonably ascribed to another cause, such as disease progression or accident.

A dose was considered non-tolerated and dose escalation stopped if ≥2 of up to 6 evaluable patients experienced a DLT at any dose level. MTD is the last dose level before the non-tolerated dose.

Lower limit of quantification for MEDI-551 was 0.1 μg/mL.

Only 1 patient was tested positive for ADA at pre-dose of Cycle 1 Day 1. However, it was considered as false-positive because the titer value was close to the cut point, and this patient was tested negative for ADA at all subsequent cycles post-baseline.

Tumour response is defined as complete remission (CR) or partial remission (PR) (Cheson BD et al 2007).

CR: Nodal Masses: (a) FDG-avid or PET positive prior to therapy; mass of any size permitted if PET negative; (b) Variably FDG-avid or PET negative; regression to normal size on CT; Spleen, Liver: Not palpable, nodules disappeared. Bone Marrow: Infiltrate cleared on repeat biopsy; if indeterminate by morphology, immunohistochemistry should be negative.

PR: Nodal Masses: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses; no increase in size of other nodes; (a) FDG-avid or PET positive prior to therapy; ≥1 PET positive at previously involved site; (b) Variably FDG-avid or PET negative; regression on CT. Spleen, Liver: ≥50% decrease in SPD of nodules (for single nodule in greatest transverse diameter); no increase in size of liver or spleen. Bone Marrow: Irrelevant if positive prior to therapy; cell type should be specified.

Tumour response is defined as complete remission (CR) or partial remission (PR) (Hallek M et al 2008).

CR: all of the following criteria have to be met, and patients have to lack disease-related constitutional symptoms; Lymphadenopathy: None; Hepatomegaly: None; Splenomegaly: None; Blood lymphocytes: \<4000/μL; Marrow: Normocellular, \<30%lymphocytes, no B-lymphoid nodules, hypocellular marrow defines CR with incomplete marrow recovery; Platelet count: \>100000/μL; Hemoglobin: \>11.0 g/dL; Neutrophils: \>1500/μL PR: at least 2 of the criteria of group A plus 1 of the criteria of group B have to be met.

Group A: Lymphadenopathy: Decrease ≥50%; Hepatomegaly: Decrease ≥50%; Splenomegaly: Decrease ≥50%; Blood lymphocytes: Decrease ≥50% from baseline; Marrow: 50% reduction in marrow infiltrate, or B-lymphoid nodules.

Group B: Platelet count: 100000/μL or increase ≥50% over baseline; Hemoglobin: \>11.0 g/dL or increase ≥50% over baseline; Neutrophils: \>1500/μL or \>50% improvement over baseline.

Tumour response is defined as complete response (CR) or partial response (PR) (Durie M et al 2006).

CR: Negative immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas and 5% or less plasma cells in bone marrow PR: ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to \<200mg per 24 h. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was ≥30%. In addition to the above listed criteria, if present at baseline, a ≥50% reduction in the size of soft tissue plasmacytomas is also required.

MedImmune LLC

AstraZeneca

2 mg/kg

4 mg/kg

8 mg/kg

12 mg/kg

Total

Age, Continuous

Sex: Female, Male

DLBCL

Disease Type (CLL: chronic lymphocytic leukemia, DLBCL: diffuse large B-cell lymphoma, FL: follicular lymphoma, MM: multiple myeloma)

Disease Type

All patients who received at least 1 dose of MEDI-551.

Medical Director

At least 1 Adverse Events (AE)

At least 1 AE of CTCAE Grade 3 or higher

At least 1 Serious Adverse Events (SAE)

Number of Participants With Adverse Events

At least 1 Dose Limiting Toxicity

CTCAE Grade 3 or higher non-hematologic toxicity

CTCAE Grade 3 or higher hematologic toxicity

All subjects in the dose escalation phase who have received MEDI-551 at Day 1 and Day 8 and completed the safety follow-up through the dose-limiting toxicity (DLT) evaluation period (28 days), or who experienced a DLT.

Number of Participants With Dose Limiting Toxicities

MEDI-551 2, 4, 8 and 12 mg/kg were evaluated

Maximum Tolerated Dose

Patients who have trough concentration data at Day 0 (pre-dose)

MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose)

Patients who have trough concentration data at Day 7

MEDI-551 Trough Concentration Levels at Day 7

Patients who have trough concentration data at Day 28

MEDI-551 Trough Concentration Levels at Day 28

Patients who have trough concentration data at Day 56

MEDI-551 Trough Concentration Levels at Day 56

Patients who have trough concentration data at Day 84

MEDI-551 Trough Concentration Levels at Day84

Patients who have trough concentration data at Day 112

MEDI-551 Trough Concentration Levels at Day 112

Patients who have trough concentration data at Day 140

MEDI-551 Trough Concentration Levels at Day 140

Patients who have trough concentration data at Day 168

MEDI-551 Trough Concentration Levels at Day 168

positive at least 1 time point

negative at all time points

Patients who have at least one post-baseline sample for Anti-MEDI-551 antibodies.

Anti-MEDI-551 Antibodies

2 mg/kg (FL)

4 mg/kg (FL)

8 mg/kg (FL)

12 mg/kg (FL)

All patients with FL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Number of Participants With Tumour Response in FL Patients

DLBCL patients in MEDI-551 2 mg/kg cohort

2 mg/kg (DLBCL)

DLBCL patients in MEDI-551 4 mg/kg cohort

4 mg/kg (DLBCL)

DLBCL patients in MEDI-551 8 mg/kg cohort

8 mg/kg (DLBCL)

DLBCL patients in MEDI-551 12 mg/kg cohort

12 mg/kg (DLBCL)

All patients with DLBCL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Number of Participants With Tumour Response in DLBCL Patients

2 mg/kg (CLL)

4 mg/kg (CLL)

8 mg/kg (CLL)

12 mg/kg (CLL)

All patients with CLL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Number of Participants With Tumour Response in CLL Patients

2 mg/kg (MM)

4 mg/kg (MM)

8 mg/kg (MM)

12 mg/kg (MM)

All patients with MM who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.

Spots Global Cancer Trial Database for A Phase 1, Dose-escalation Study of MEDI-551 in Japanese Adult Patients With Relapsed or Refractory Advanced B-cell Malignancies

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial