Diffuse, Large B-Cell, Lymphoma, Follicular Lymphoma, Grade 3b, Transformed Lymphoma / DLBCL
Conditions
Keywords
Antibodies, Monoclonal, SGN-19A, Denintuzumab Mafodotin, DLBCL, Antibody-Drug Conjugate, Antigens, CD19, Hematologic Diseases, Immune System Diseases, Immunoproliferative Disorders, Immunotherapy, Lymphatic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Monomethyl auristatin F, Neoplasms, Neoplasms by Histologic Type, Transformed Lymphoma / DLBCL, Cyclophosphamide, Doxorubicin, Liposomal doxorubicin, Prednisone, Rituximab, Vincristine, Alkylating Agents, Anti-Inflammatory Agents, Antibiotic, Antineoplastic, Antimitotic Agents, Antineoplastic Agents, Alkylating, Antineoplastic Agents, Phytogenic Antirheumatic Agents, Glucocorticoids, Drug Therapy, Follicular Lymphoma Grade 3b, immunosuppressive agents
Brief summary
This is a Phase 2 study to evaluate the combination of denintuzumab mafodotin in combination with RCHOP or RCHP compared with RCHOP alone as front-line therapy in patients with diffuse large B-cell lymphoma or follicular lymphoma Grade 3b.
Detailed description
In Part A of the study, patients will be randomized 1:1 to receive denintuzumab mafodotin plus RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or denintuzumab mafodotin plus RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) to assess the safety of these 2 combination regimens. Part B of the study is designed to evaluate the antitumor activity and safety of denintuzumab mafodotin in combination with either RCHOP or RCHP (Experimental Arm) compared with RCHOP alone (Comparator Arm).
Interventions
SGN-CD19A at 3 mg/kg will be administered every 6 weeks via intravenous (IV) infusion, up to a maximum of three (3) doses, on Day 1 of Cycles 1, 3, and 5 of 21-day cycles
DRUGrituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
DRUGcyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
DRUGdoxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
DRUGvincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
DRUGprednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
Sponsors
Seagen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Treatment-naive patients with histologically confirmed systemic de novo or transformed diffuse large B-cell lymphoma (DLBCL) (from follicular or marginal zone lymphoma), or follicular lymphoma (FL) Grade 3b; * patients must have high intermediate or high risk disease * Tumor tissue available from most recent biopsy to determine cell of origin * Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease greater than 1.5cm diameter * Eastern Cooperative Oncology Group performance status ≤2 * Age 18 years or older * Adequate study baseline laboratory parameters
Exclusion criteria
* Previous history of treated indolent lymphoma * History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years * History of progressive multifocal leukoencephalopathy * Cerebral/meningeal disease related to the underlying malignancy * Patients with the following ocular conditions: corneal disorders, monocular vision (ie. best corrected visual acuity greater than or equal to 20/200 in one eye), or active ocular disorders requiring treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B Outcome Measure: Complete Response Rate (CR) | N/A - Endpoint not assessed | Study did not progress to Part B. |
| Part A and Part B Outcome Measure: Incidence of Adverse Events | 54.7 weeks | Part A data only; study did not progress to Part B. |
| Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Up to 183 days | Part A data reported; study did not progress to Part B. Laboratory abnormalities Grade 1+ are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) at End Of Treatment (EOT) Between Study Arms in Part B | N/A - Endpoint not assessed | Study did not progress to Part B. |
| Event-free Survival (EFS) Between Study Arms in Part B | N/A - Endpoint not assessed | Study did not progress to Part B |
| Duration of Objective Response and of Complete Response (CR) Between Study Arms in Part B | N/A - Endpoint not assessed | Study did not progress to Part B. |
| Progression-free Survival (PFS) Between Study Arms in Part B | N/A - Endpoint not assessed | Study did not progress to Part B. |
| Overall Survival (OS) Between Study Arms in Part B | N/A - Endpoint not assessed | Study did not progress to Part B. |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Denintuzumab Mafodotin + RCHP Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin: SGN-CD19A at 3 mg/kg will be administered every 6 weeks via intravenous (IV) infusion, up to a maximum of three (3) doses, on Day 1 of Cycles 1, 3, and 5 of 21-day cycles
rituximab: 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
cyclophosphamide: 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
doxorubicin: 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
prednisone: 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles | 11 |
| Denintuzumab Mafodotin + RCHOP Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin: SGN-CD19A at 3 mg/kg will be administered every 6 weeks via intravenous (IV) infusion, up to a maximum of three (3) doses, on Day 1 of Cycles 1, 3, and 5 of 21-day cycles
rituximab: 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
cyclophosphamide: 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
doxorubicin: 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
vincristine: 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
prednisone: 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles | 13 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 2 | 2 | 0 | 0 |
| Overall Study | Study Termination by Sponsor | 9 | 11 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Denintuzumab Mafodotin + RCHOP | Denintuzumab Mafodotin + RCHP |
|---|---|---|---|
| Age, Continuous | 69 years | 72 years | 67 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0: Normal activity | 5 Participants | 3 Participants | 2 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1: Symptoms, but ambulatory | 13 Participants | 5 Participants | 8 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2: In bed less than 50% of the time | 6 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 13 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 22 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Female | 9 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 15 Participants | 9 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 11 | 2 / 13 |
| other Total, other adverse events | 11 / 11 | 13 / 13 |
| serious Total, serious adverse events | 5 / 11 | 4 / 13 |
Outcome results
Primary
Part A and Part B Outcome Measure: Incidence of Adverse Events
Part A data only; study did not progress to Part B.
Time frame: 54.7 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any AE with Outcome of Death | 2 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-emergent adverse event (TEAE) | 11 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-Related SAE | 4 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Grade 3-5 TEAE | 11 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Serious Adverse Event (SAE) | 5 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-related Adverse Event (AE) | 10 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any DM Treatment-Related SAE | 2 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any DM treatment-related AE | 9 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any RCHOP/RCHP treatment-related AE | 10 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any DM treatment-related AE | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any RCHOP/RCHP treatment-related AE | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any AE with Outcome of Death | 1 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Serious Adverse Event (SAE) | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-Related SAE | 3 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any DM Treatment-Related SAE | 2 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-emergent adverse event (TEAE) | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Grade 3-5 TEAE | 12 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Adverse Events | Any Treatment-related Adverse Event (AE) | 13 Participants |
Primary
Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities
Part A data reported; study did not progress to Part B. Laboratory abnormalities Grade 1+ are reported.
Time frame: Up to 183 days
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Alanine aminotransferase increased | 3 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypoalbuminemia | 3 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Alkaline phosphatase increased | 5 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Aspartate aminotransferase increased | 5 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Blood bilirubin increased | 0 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypercalcemia | 3 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyperglycemia | 8 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypoglycemia | 1 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypomagnesemia | 4 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypophosphatemia | 5 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypokalemia | 6 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypernatremia | 1 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyponatremia | 4 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyperuricemia | 0 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Anemia | 10 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Leukopenia | 10 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Lymphopenia | 9 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Neutropenia | 9 Participants |
| Denintuzumab Mafodotin + RCHP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Thrombocytopenia | 10 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypomagnesemia | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Alanine aminotransferase increased | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Lymphopenia | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypoalbuminemia | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypophosphatemia | 5 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Alkaline phosphatase increased | 8 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Anemia | 12 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Aspartate aminotransferase increased | 9 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypokalemia | 7 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Blood bilirubin increased | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Thrombocytopenia | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypernatremia | 1 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Leukopenia | 13 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyperglycemia | 11 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyponatremia | 12 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypoglycemia | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Neutropenia | 11 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hypermagnesemia | 4 Participants |
| Denintuzumab Mafodotin + RCHOP | Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities | Hyperuricemia | 1 Participants |
Primary
Part B Outcome Measure: Complete Response Rate (CR)
Study did not progress to Part B.
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.
Secondary
Duration of Objective Response and of Complete Response (CR) Between Study Arms in Part B
Study did not progress to Part B.
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.
Secondary
Event-free Survival (EFS) Between Study Arms in Part B
Study did not progress to Part B
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.
Secondary
Objective Response Rate (ORR) at End Of Treatment (EOT) Between Study Arms in Part B
Study did not progress to Part B.
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.
Secondary
Overall Survival (OS) Between Study Arms in Part B
Study did not progress to Part B.
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.
Secondary
Progression-free Survival (PFS) Between Study Arms in Part B
Study did not progress to Part B.
Time frame: N/A - Endpoint not assessed
Population: Endpoint not assessed; study did not progress to Part B.