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

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01957579
Collaborator
MedImmune LLC (Industry)
32
Enrollment
3
Locations
1
Arm
51.7
Actual Duration (Months)
10.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
May 25, 2011
Actual Primary Completion Date :
Sep 15, 2015
Actual Study Completion Date :
Sep 15, 2015

Arms and Interventions

ArmIntervention/Treatment
Experimental: MEDI-551

Drug: MEDI-551
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

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Adverse Events [From baseline to 30 days after the last dose of study drug]

Secondary Outcome Measures

  1. Number of Participants With Dose Limiting Toxicities [From baseline to 28 days after the first dose of study drug]

    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.

  2. Maximum Tolerated Dose [From baseline to 28 days after the first dose of study drug]

    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.

  3. MEDI-551 Trough Concentration Levels at Day 0 (Pre-dose) [Day 0 (pre-dose)]

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

  4. MEDI-551 Trough Concentration Levels at Day 7 [Day 7]

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

  5. MEDI-551 Trough Concentration Levels at Day 28 [Day 28]

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

  6. MEDI-551 Trough Concentration Levels at Day 56 [Day 56]

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

  7. MEDI-551 Trough Concentration Levels at Day84 [Day 84]

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

  8. MEDI-551 Trough Concentration Levels at Day 112 [Day 112]

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

  9. MEDI-551 Trough Concentration Levels at Day 140 [Day 140]

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

  10. MEDI-551 Trough Concentration Levels at Day 168 [Day 168]

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

  11. Anti-MEDI-551 Antibodies [From baseline to 30 days after the last dose of study drug]

    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.

  12. Number of Participants With Tumour Response in FL Patients [From the baseline to 30 days after the last dose of study drug]

    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.

  13. Number of Participants With Tumour Response in DLBCL Patients [From the baseline to 30 days after the last dose of study drug]

    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.

  14. Number of Participants With Tumour Response in CLL Patients [From the baseline to 30 days after the last dose of study drug]

    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.

  15. Number of Participants With Tumour Response in MM Patients [From the baseline to30 days after the last dose of study drug]

    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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
20 Years to 130 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Japanese men or women at least 20 years of age

  • Histologically confirmed CLL (excluding small lymphocytic lymphoma (SLL)), DLBCL, FL, or MM.

  • Karnofsky Performance Status ≥70;

  • Life expectancy of ≥12 weeks

Exclusion Criteria:
  • Any available standard line of therapy known to be life-prolonging or life-saving

  • Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic or hormonal therapy for treatment of cancer

  • Previous therapy directed against CD19, such as monoclonal antibodies or MAb conjugates

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Research SiteFukuoka-shiJapan
2Research SiteIsehara-shiJapan
3Research SiteNagoya-shiJapan

Sponsors and Collaborators

  • AstraZeneca
  • MedImmune LLC

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01957579
Other Study ID Numbers:
  • D2850C00001
  • NCT01377116
First Posted:
Oct 8, 2013
Last Update Posted:
Jun 12, 2017
Last Verified:
May 1, 2017
Keywords provided by AstraZeneca
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsFirst patient enrolled on 25 May 2011. Last patient last visit on 15 September 2015.
Pre-assignment DetailA total of 32 patients were enrolled into the study. Twelve patients were screen failures, thus 20 patients received MEDI-551.
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Period Title: Overall Study
STARTED3746
COMPLETED3626
NOT COMPLETED0120

Baseline Characteristics

Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kgTotal
Arm/Group DescriptionMEDI-551 2mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kgTotal of all reporting groups
Overall Participants374620
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
50.3
(8.1)
57.4
(10.5)
67.0
(8.7)
67.3
(11.4)
61.3
(11.4)
Sex: Female, Male (Count of Participants)
Female
2
66.7%
5
71.4%
0
0%
3
50%
10
50%
Male
1
33.3%
2
28.6%
4
100%
3
50%
10
50%
Disease Type (Number) [Number]
CLL
1
33.3%
0
0%
0
0%
1
16.7%
2
10%
DLBCL
0
0%
2
28.6%
2
50%
2
33.3%
6
30%
FL
2
66.7%
4
57.1%
2
50%
3
50%
11
55%
MM
0
0%
1
14.3%
0
0%
0
0%
1
5%

Outcome Measures

1. Primary Outcome
TitleNumber of Participants With Adverse Events
Description
Time FrameFrom baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
All patients who received at least 1 dose of MEDI-551.
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3746
At least 1 Adverse Events (AE)
3
100%
6
85.7%
4
100%
6
100%
At least 1 AE of CTCAE Grade 3 or higher
2
66.7%
2
28.6%
1
25%
3
50%
At least 1 Serious Adverse Events (SAE)
1
33.3%
0
0%
0
0%
0
0%
2. Secondary Outcome
TitleNumber of Participants With Dose Limiting Toxicities
DescriptionA 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.
Time FrameFrom baseline to 28 days after the first dose of study drug

Outcome Measure Data

Analysis Population Description
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.
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3636
At least 1 Dose Limiting Toxicity
0
0%
1
14.3%
0
0%
2
33.3%
CTCAE Grade 3 or higher non-hematologic toxicity
0
0%
1
14.3%
0
0%
1
16.7%
CTCAE Grade 3 or higher hematologic toxicity
0
0%
0
0%
0
0%
1
16.7%
3. Secondary Outcome
TitleMaximum Tolerated Dose
DescriptionA 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.
Time FrameFrom baseline to 28 days after the first dose of study drug

Outcome Measure Data

Analysis Population Description
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.
Arm/Group TitleMEDI-551
Arm/Group DescriptionMEDI-551 2, 4, 8 and 12 mg/kg were evaluated
Measure Participants18
Number [mg/kg]
8
4. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 0 (Pre-dose)
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 0 (pre-dose)

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 0 (pre-dose)
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3746
Mean (Standard Deviation) [μg/mL]
NA
(NA)
NA
(NA)
NA
(NA)
NA
(NA)
5. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 7
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 7

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 7
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3644
Mean (Standard Deviation) [μg/mL]
21.3
(8.65)
39.2
(9.13)
91.9
(31.1)
104
(29.0)
6. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 28
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 28

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 28
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3534
Mean (Standard Deviation) [μg/mL]
23.2
(5.82)
36.2
(5.34)
103
(29.0)
115
(21.3)
7. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 56
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 56

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 56
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3534
Mean (Standard Deviation) [μg/mL]
22.0
(4.92)
33.2
(6.92)
89.5
(13.9)
114
(33.1)
8. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day84
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 84

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 84
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3434
Mean (Standard Deviation) [μg/mL]
21.7
(4.40)
33.7
(4.24)
91.6
(9.25)
103
(26.3)
9. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 112
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 112

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 112
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3424
Mean (Standard Deviation) [μg/mL]
22.9
(3.10)
35.3
(5.07)
85.5
(NA)
114
(64.4)
10. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 140
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 140

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 140
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants2424
Mean (Standard Deviation) [μg/mL]
22.1
(NA)
36.3
(10.5)
86.1
(NA)
117
(62.0)
11. Secondary Outcome
TitleMEDI-551 Trough Concentration Levels at Day 168
DescriptionLower limit of quantification for MEDI-551 was 0.1 μg/mL.
Time FrameDay 168

Outcome Measure Data

Analysis Population Description
Patients who have trough concentration data at Day 168
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants2322
Mean (Standard Deviation) [μg/mL]
20.0
(NA)
31.4
(8.30)
94.1
(NA)
82.1
(NA)
12. Secondary Outcome
TitleAnti-MEDI-551 Antibodies
DescriptionOnly 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.
Time FrameFrom baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
Patients who have at least one post-baseline sample for Anti-MEDI-551 antibodies.
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2 mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
Measure Participants3746
positive at least 1 time point
0
0%
0
0%
1
25%
0
0%
negative at all time points
3
100%
7
100%
3
75%
6
100%
13. Secondary Outcome
TitleNumber of Participants With Tumour Response in FL Patients
DescriptionTumour 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.
Time FrameFrom the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
All patients with FL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.
Arm/Group Title2 mg/kg (FL)4 mg/kg (FL)8 mg/kg (FL)12 mg/kg (FL)
Arm/Group DescriptionFL patients in MEDI-551 2 mg/kg cohortFL patients in MEDI-551 4 mg/kg cohortFL patients in MEDI-551 8 mg/kg cohortFL patients in MEDI-551 12 mg/kg cohort
Measure Participants2423
Number [Participants]
2
66.7%
3
42.9%
2
50%
2
33.3%
14. Secondary Outcome
TitleNumber of Participants With Tumour Response in DLBCL Patients
DescriptionTumour 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.
Time FrameFrom the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
All patients with DLBCL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.
Arm/Group Title2 mg/kg (DLBCL)4 mg/kg (DLBCL)8 mg/kg (DLBCL)12 mg/kg (DLBCL)
Arm/Group DescriptionDLBCL patients in MEDI-551 2 mg/kg cohortDLBCL patients in MEDI-551 4 mg/kg cohortDLBCL patients in MEDI-551 8 mg/kg cohortDLBCL patients in MEDI-551 12 mg/kg cohort
Measure Participants0222
Number [Participants]
0
0%
1
14.3%
2
50%
15. Secondary Outcome
TitleNumber of Participants With Tumour Response in CLL Patients
DescriptionTumour 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.
Time FrameFrom the baseline to 30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
All patients with CLL who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.
Arm/Group Title2 mg/kg (CLL)4 mg/kg (CLL)8 mg/kg (CLL)12 mg/kg (CLL)
Arm/Group DescriptionCLL patients in MEDI-551 2 mg/kg cohortCLL patients in MEDI-551 4 mg/kg cohortCLL patients in MEDI-551 8 mg/kg cohortCLL patients in MEDI-551 12 mg/kg cohort
Measure Participants1001
Number [Participants]
1
33.3%
0
0%
16. Secondary Outcome
TitleNumber of Participants With Tumour Response in MM Patients
DescriptionTumour 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.
Time FrameFrom the baseline to30 days after the last dose of study drug

Outcome Measure Data

Analysis Population Description
All patients with MM who received at least 1 dose of MEDI-551 and completed at least 1 post-baseline disease assessment.
Arm/Group Title2 mg/kg (MM)4 mg/kg (MM)8 mg/kg (MM)12 mg/kg (MM)
Arm/Group DescriptionMM patients in MEDI-551 2 mg/kg cohortMM patients in MEDI-551 4 mg/kg cohortMM patients in MEDI-551 8 mg/kg cohortMM patients in MEDI-551 12 mg/kg cohort
Measure Participants0100
Number [Participants]
0
0%

Adverse Events

Time FrameAEs were collected throughout the study, from informed consent until the end of 30 days after study treatment. The follow-up period is defined as 3 months after study treatment is discontinued.
Adverse Event Reporting Description
Arm/Group Title2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Arm/Group DescriptionMEDI-551 2mg/kgMEDI-551 4 mg/kgMEDI-551 8 mg/kgMEDI-551 12 mg/kg
All Cause Mortality
2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total/ (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Infections and infestations
Epiglottitis1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Other (Not Including Serious) Adverse Events
2 mg/kg4 mg/kg8 mg/kg12 mg/kg
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total3/3 (100%) 6/7 (85.7%) 4/4 (100%) 6/6 (100%)
Blood and lymphatic system disorders
Leukopenia0/3 (0%) 1/7 (14.3%) 1/4 (25%) 1/6 (16.7%)
Neutropenia0/3 (0%) 1/7 (14.3%) 0/4 (0%) 1/6 (16.7%)
Febrile neutropenia0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Lymphadenitis1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Eye disorders
Conjunctivitis allergic0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Eyelid oedema0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Gastrointestinal disorders
Constipation0/3 (0%) 1/7 (14.3%) 0/4 (0%) 1/6 (16.7%)
Abdominal pain upper0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Diarrhoea0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Dry mouth0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Proctalgia0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Stomatitis0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
General disorders
Fatigue1/3 (33.3%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Influenza like illness1/3 (33.3%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Pyrexia0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Hepatobiliary disorders
Hepatic function abnormal0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Infections and infestations
Nasopharyngitis1/3 (33.3%) 0/7 (0%) 1/4 (25%) 1/6 (16.7%)
Upper respiratory tract infection1/3 (33.3%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Bronchitis0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Oral candidiasis0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Injury, poisoning and procedural complications
Infusion related reaction2/3 (66.7%) 1/7 (14.3%) 3/4 (75%) 3/6 (50%)
Investigations
White blood cell count decreased2/3 (66.7%) 2/7 (28.6%) 0/4 (0%) 0/6 (0%)
Lymphocyte count decreased1/3 (33.3%) 2/7 (28.6%) 0/4 (0%) 0/6 (0%)
Neutrophil count decreased1/3 (33.3%) 2/7 (28.6%) 0/4 (0%) 0/6 (0%)
Platelet count decreased0/3 (0%) 1/7 (14.3%) 1/4 (25%) 0/6 (0%)
Aspartate aminotransferase increased1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Blood cholesterol increased0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Blood creatine phosphokinase increased0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Blood creatinine increased0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Blood lactate dehydrogenase increased1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Blood triglycerides increased1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Metabolism and nutrition disorders
Hypertriglyceridaemia1/3 (33.3%) 1/7 (14.3%) 4/4 (100%) 0/6 (0%)
Musculoskeletal and connective tissue disorders
Monarthritis0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Myalgia0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Spinal osteoarthritis0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Musculoskeletal chest pain0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Musculoskeletal stiffness0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholesteatoma0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Sebaceous adenoma0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Nervous system disorders
Headache0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Peripheral sensory neuropathy0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Psychiatric disorders
Insomnia0/3 (0%) 1/7 (14.3%) 0/4 (0%) 1/6 (16.7%)
Renal and urinary disorders
Calculus ureteric1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Haematuria1/3 (33.3%) 0/7 (0%) 0/4 (0%) 0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Upper respiratory tract inflammation0/3 (0%) 0/7 (0%) 0/4 (0%) 1/6 (16.7%)
Skin and subcutaneous tissue disorders
Rash1/3 (33.3%) 2/7 (28.6%) 0/4 (0%) 0/6 (0%)
Drug eruption0/3 (0%) 0/7 (0%) 1/4 (25%) 0/6 (0%)
Eczema0/3 (0%) 1/7 (14.3%) 0/4 (0%) 0/6 (0%)
Vascular disorders
Hypertension0/3 (0%) 2/7 (28.6%) 0/4 (0%) 0/6 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleMedical Director
OrganizationMedImmune, LLC
Phone
EmailClinicalTrialTransparency@astrazeneca.com
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01957579
Other Study ID Numbers:
  • D2850C00001
  • NCT01377116
First Posted:
Oct 8, 2013
Last Update Posted:
Jun 12, 2017
Last Verified:
May 1, 2017