Trial Outcomes & Findings for Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma (NCT NCT02592876)
NCT ID: NCT02592876
Last Updated: 2019-05-17
Results Overview
Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
81 participants
Primary outcome timeframe
Up to 4 months
Results posted on
2019-05-17
Participant Flow
Participant milestones
| Measure |
RICE
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Overall Study
STARTED
|
41
|
40
|
|
Overall Study
Received Study Drug
|
40
|
40
|
|
Overall Study
Completed Treatment
|
34
|
32
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
41
|
40
|
Reasons for withdrawal
| Measure |
RICE
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
3
|
3
|
|
Overall Study
Study Termination by Sponsor
|
32
|
27
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Death
|
6
|
9
|
Baseline Characteristics
Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma
Baseline characteristics by cohort
| Measure |
RICE
n=41 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
Total
n=81 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
28 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
13 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Age, Continuous
|
60.0 years
n=5 Participants
|
62.5 years
n=7 Participants
|
61.0 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
37 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
37 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
73 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
41 participants
n=5 Participants
|
40 participants
n=7 Participants
|
81 participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 0
|
17 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 1
|
21 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
42 Participants
n=5 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) Performance Status
Grade 2
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 4 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Complete Remission Rate Per Independent Review Facility
|
18 Participants
|
25 Participants
|
SECONDARY outcome
Timeframe: Up to 4 monthsPopulation: The safety analysis set includes all patients who received any amount of denintuzumab mafodotin or any component of RICE. Treatment group is determined using the actual treatment arm received, regardless of the randomization treatment assignment.
Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. AE severity and seriousness are assessed independently. 'Severity' characterizes the intensity of an AE and is graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. An AE is considered 'serious' if it is life-threatening, fatal, requires hospitalization, or is otherwise considered to be medically significant.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Number of Participants With Adverse Events (AEs)
Treatment-emergent AE (TEAE)
|
39 Participants
|
40 Participants
|
|
Number of Participants With Adverse Events (AEs)
Treatment-related AEs
|
38 Participants
|
40 Participants
|
|
Number of Participants With Adverse Events (AEs)
Grade 3 or Higher TEAEs
|
31 Participants
|
38 Participants
|
|
Number of Participants With Adverse Events (AEs)
Serious AEs (SAEs)
|
13 Participants
|
19 Participants
|
|
Number of Participants With Adverse Events (AEs)
Treatment-related SAEs
|
9 Participants
|
13 Participants
|
|
Number of Participants With Adverse Events (AEs)
AEs Leading to Dose Delay
|
3 Participants
|
8 Participants
|
|
Number of Participants With Adverse Events (AEs)
AEs Leading to Dose Reduction
|
3 Participants
|
5 Participants
|
|
Number of Participants With Adverse Events (AEs)
AEs Leading to Treatment Discontinuation
|
2 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 4 monthsPopulation: The safety analysis set includes all patients who received any amount of denintuzumab mafodotin or any component of RICE. Treatment group is determined using the actual treatment arm received, regardless of the randomization treatment assignment.
Number of participants who experienced a maximum post-baseline laboratory toxicity of Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03).
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Number of Participants With Laboratory Abnormalities
Any Hematology Test
|
37 Participants
|
37 Participants
|
|
Number of Participants With Laboratory Abnormalities
Hemoglobin Low
|
19 Participants
|
18 Participants
|
|
Number of Participants With Laboratory Abnormalities
Leukocytes High
|
1 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities
Leukocytes Low
|
23 Participants
|
24 Participants
|
|
Number of Participants With Laboratory Abnormalities
Lymphocytes High
|
2 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities
Lymphocytes Low
|
34 Participants
|
31 Participants
|
|
Number of Participants With Laboratory Abnormalities
Neutrophils Low
|
22 Participants
|
22 Participants
|
|
Number of Participants With Laboratory Abnormalities
Platelets Low
|
26 Participants
|
35 Participants
|
|
Number of Participants With Laboratory Abnormalities
Any Chemistry Test
|
18 Participants
|
16 Participants
|
|
Number of Participants With Laboratory Abnormalities
Alanine Aminotransferase High
|
3 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Abnormalities
Aspartate Aminotransferase High
|
1 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities
Calcium High
|
4 Participants
|
0 Participants
|
|
Number of Participants With Laboratory Abnormalities
Calcium Low
|
0 Participants
|
2 Participants
|
|
Number of Participants With Laboratory Abnormalities
Creatinine High
|
0 Participants
|
1 Participants
|
|
Number of Participants With Laboratory Abnormalities
Glucose High
|
4 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Abnormalities
Phosphate Low
|
9 Participants
|
8 Participants
|
|
Number of Participants With Laboratory Abnormalities
Potassium Low
|
3 Participants
|
5 Participants
|
|
Number of Participants With Laboratory Abnormalities
Sodium Low
|
4 Participants
|
3 Participants
|
|
Number of Participants With Laboratory Abnormalities
Urate High
|
2 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 4 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
ORR is defined as the proportion of patients with complete remission (CR) or partial remission (PR) per independent review facility (IRF) at the end of treatment.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Objective Response Rate (ORR)
|
30 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: Up to 27.9 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
Defined as the time from the start of the first radiographic documentation of CR per investigator to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Duration of Complete Response (CR)
|
NA months
Insufficient number of events observed
|
NA months
Insufficient number of events observed
|
SECONDARY outcome
Timeframe: Up to 27.9 monthsDuration of OR is defined as the time from the start of the first radiographic documentation of OR per investigator to the first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Duration of Objective Response (OR)
|
NA months
Interval 8.15 to
Insufficient number of events observed
|
NA months
Insufficient number of events observed
|
SECONDARY outcome
Timeframe: Up to 30 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
PFS is defined as the time from randomization to first documentation of disease progression per investigator, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Progression-free Survival (PFS)
|
NA months
Interval 2.86 to
Insufficient number of events observed
|
NA months
Interval 5.82 to
Insufficient number of events observed
|
SECONDARY outcome
Timeframe: Up to 30 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Overall Survival (OS)
|
NA months
Insufficient number of events observed
|
NA months
Interval 10.97 to
Insufficient number of events observed
|
SECONDARY outcome
Timeframe: Up to 30 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
Defined as the number of patients who are able to adequately mobilize PBSC per investigator assessment on or after completion of study treatment, prior to subsequent anticancer therapy.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization
Patients with sufficient stem cell collection
|
26 Participants
|
21 Participants
|
|
Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization
Patients with attempted stem cell collection(s)
|
28 Participants
|
24 Participants
|
SECONDARY outcome
Timeframe: Up to 30 monthsPopulation: The modified Intent-to-Treat (mITT) analysis set includes all patients who were randomized to the recommended dose level of 19A+RICE or RICE and received at least 1 cycle of study treatment.
Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy.
Outcome measures
| Measure |
RICE
n=40 Participants
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 Participants
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)
Patients planned to receive ASCT at EOT
|
28 Participants
|
25 Participants
|
|
Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)
Patients who received ASCT at EOT
|
25 Participants
|
22 Participants
|
Adverse Events
RICE
Serious events: 13 serious events
Other events: 40 other events
Deaths: 6 deaths
19A+RICE
Serious events: 19 serious events
Other events: 40 other events
Deaths: 9 deaths
Serious adverse events
| Measure |
RICE
n=40 participants at risk
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 participants at risk
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
15.0%
6/40 • Up to 30 months
|
20.0%
8/40 • Up to 30 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.5%
1/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Cardiac disorders
Tachycardia
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Intestinal fistula
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Pancreatitis acute
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
General disorders
Pyrexia
|
2.5%
1/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Infections and infestations
External ear cellulitis
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Infections and infestations
Lung infection
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Infections and infestations
Otitis externa
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Infections and infestations
Pneumonia
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Infections and infestations
Rhinovirus infection
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Infections and infestations
Sepsis
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Infections and infestations
Septic shock
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Gastrointestinal stoma complication
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Hip fracture
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Transfusion reaction
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Investigations
Hepatic enzyme increased
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Investigations
Platelet count decreased
|
0.00%
0/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Investigations
White blood cell count decreased
|
0.00%
0/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant pleural effusion
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Nervous system disorders
Depressed level of consciousness
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Nervous system disorders
Headache
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Nervous system disorders
Neurotoxicity
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Nervous system disorders
Syncope
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Renal and urinary disorders
Acute kidney injury
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal mass
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Vascular disorders
Hypotension
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Vascular disorders
Vena cava thrombosis
|
2.5%
1/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
Other adverse events
| Measure |
RICE
n=40 participants at risk
Rituximab, ifosfamide, carboplatin, and etoposide
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
19A+RICE
n=40 participants at risk
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
denintuzumab mafodotin: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
rituximab: 375 mg/m2 by IV infusion, every 3 weeks for up to 3 cycles
ifosfamide: 5000 mg/m2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
carboplatin: AUC 5 by IV infusion, every 3 weeks for up to 3 cycles
etoposide: 100 mg/m2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
57.5%
23/40 • Up to 30 months
|
47.5%
19/40 • Up to 30 months
|
|
Blood and lymphatic system disorders
Neutropenia
|
7.5%
3/40 • Up to 30 months
|
22.5%
9/40 • Up to 30 months
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
37.5%
15/40 • Up to 30 months
|
57.5%
23/40 • Up to 30 months
|
|
Eye disorders
Dry eye
|
10.0%
4/40 • Up to 30 months
|
25.0%
10/40 • Up to 30 months
|
|
Eye disorders
Foreign body sensation in eyes
|
0.00%
0/40 • Up to 30 months
|
10.0%
4/40 • Up to 30 months
|
|
Eye disorders
Keratitis
|
0.00%
0/40 • Up to 30 months
|
10.0%
4/40 • Up to 30 months
|
|
Eye disorders
Keratopathy
|
7.5%
3/40 • Up to 30 months
|
67.5%
27/40 • Up to 30 months
|
|
Eye disorders
Photophobia
|
2.5%
1/40 • Up to 30 months
|
20.0%
8/40 • Up to 30 months
|
|
Eye disorders
Vision blurred
|
12.5%
5/40 • Up to 30 months
|
65.0%
26/40 • Up to 30 months
|
|
Gastrointestinal disorders
Abdominal pain
|
2.5%
1/40 • Up to 30 months
|
12.5%
5/40 • Up to 30 months
|
|
Gastrointestinal disorders
Constipation
|
27.5%
11/40 • Up to 30 months
|
30.0%
12/40 • Up to 30 months
|
|
Gastrointestinal disorders
Diarrhoea
|
12.5%
5/40 • Up to 30 months
|
22.5%
9/40 • Up to 30 months
|
|
Gastrointestinal disorders
Dry mouth
|
7.5%
3/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Dyspepsia
|
7.5%
3/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
7.5%
3/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Gastrointestinal disorders
Nausea
|
62.5%
25/40 • Up to 30 months
|
65.0%
26/40 • Up to 30 months
|
|
Gastrointestinal disorders
Stomatitis
|
5.0%
2/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Gastrointestinal disorders
Vomiting
|
27.5%
11/40 • Up to 30 months
|
30.0%
12/40 • Up to 30 months
|
|
General disorders
Asthenia
|
5.0%
2/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
General disorders
Chills
|
12.5%
5/40 • Up to 30 months
|
12.5%
5/40 • Up to 30 months
|
|
General disorders
Fatigue
|
52.5%
21/40 • Up to 30 months
|
47.5%
19/40 • Up to 30 months
|
|
General disorders
Oedema peripheral
|
17.5%
7/40 • Up to 30 months
|
12.5%
5/40 • Up to 30 months
|
|
General disorders
Pyrexia
|
10.0%
4/40 • Up to 30 months
|
10.0%
4/40 • Up to 30 months
|
|
Injury, poisoning and procedural complications
Contusion
|
5.0%
2/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Investigations
Alanine aminotransferase increased
|
5.0%
2/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
2/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Investigations
Blood creatinine increased
|
7.5%
3/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Investigations
Platelet count decreased
|
0.00%
0/40 • Up to 30 months
|
15.0%
6/40 • Up to 30 months
|
|
Investigations
Weight decreased
|
5.0%
2/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.0%
8/40 • Up to 30 months
|
17.5%
7/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Dehydration
|
7.5%
3/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.5%
3/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
15.0%
6/40 • Up to 30 months
|
17.5%
7/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
20.0%
8/40 • Up to 30 months
|
17.5%
7/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.5%
1/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
7.5%
3/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.5%
1/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
10.0%
4/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.5%
1/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Nervous system disorders
Dizziness
|
12.5%
5/40 • Up to 30 months
|
15.0%
6/40 • Up to 30 months
|
|
Nervous system disorders
Dysgeusia
|
7.5%
3/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Nervous system disorders
Headache
|
17.5%
7/40 • Up to 30 months
|
22.5%
9/40 • Up to 30 months
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/40 • Up to 30 months
|
10.0%
4/40 • Up to 30 months
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
10.0%
4/40 • Up to 30 months
|
0.00%
0/40 • Up to 30 months
|
|
Nervous system disorders
Syncope
|
7.5%
3/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
|
Psychiatric disorders
Insomnia
|
7.5%
3/40 • Up to 30 months
|
15.0%
6/40 • Up to 30 months
|
|
Renal and urinary disorders
Dysuria
|
7.5%
3/40 • Up to 30 months
|
2.5%
1/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
2/40 • Up to 30 months
|
15.0%
6/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.5%
7/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
7.5%
3/40 • Up to 30 months
|
10.0%
4/40 • Up to 30 months
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
10.0%
4/40 • Up to 30 months
|
15.0%
6/40 • Up to 30 months
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
12.5%
5/40 • Up to 30 months
|
17.5%
7/40 • Up to 30 months
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.0%
2/40 • Up to 30 months
|
7.5%
3/40 • Up to 30 months
|
|
Vascular disorders
Hypotension
|
5.0%
2/40 • Up to 30 months
|
5.0%
2/40 • Up to 30 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place