QUILT-3.002: N-803 in Patients With Relapse/Refractory iN... | NCT02384954

NCT02384954

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Intervention Names
Phase 1 Cohort 1: N-803 - IV 1 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 2: N-803 - IV 3 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 3: N-803 - IV 6 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 4: N-803 - SQ 6 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 5: N-803 - SQ 10 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 6: N-803 - SQ 15 ug/kg	Experimental	Biological: Rituximab Biological: N-803
Phase 1 Cohort 7: N-803 - SQ 20 ug/kg	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rituximab	Biological	Intravenous infusion 375 mg/m^2.	Phase 1 Cohort 1: N-803 - IV 1 ug/kg Phase 1 Cohort 2: N-803 - IV 3 ug/kg Phase 1 Cohort 3: N-803 - IV 6 ug/kg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
MTD or MED of N-803: IV 1, 3, 6 μg/kg, SQ 6, 10, 15, 20 μg/kg	Maximum Tolerated Dose level (MTD) is defined as a dose level at which <2 out of 6 patients experienced Dose Limiting Toxicity (DLT) and that is one level below a dose that was not tolerated. Minimal Efficacious Dose (MED) is defined as a dose level which produces an Absolute Lymphocyte Count (ALC) ≥25,000/μL sustained for 14 days or a total WBC ≥35,000/μL sustained for 14 days among 2/3 or 4/6 of patients. The elevated ALC cannot be attributed to circulating lymphoma cells. Dose levels for N-803 1, 3, 6 μg/kg IV, and 6, 10, 15, 20 μg/kg subcutaneous (SQ) were used to determine the MTD or MED.	9 months
Number of Participants With Treatment Emergent Adverse Events	Treatment Emergent Adverse Event is defined as any AE that begins or worsens in grade after the start of study treatment until 30 days after the last dose of study treatment or end of study period, whichever is later.	30 days after last dose, up to 40 weeks
Overall Response Rate	For Phase 1 and 2, overall response rate (ORR) will be calculated as the ratio of the number of patients who demonstrated response (CR+PR) divided by the number of patients in the Evaluable population. Response and disease progression criteria were defined by the 2007 IHP response assessments for malignant lymphoma.	60 months

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of iNHL (Follicular lymphoma grade 1, 2, 3a; marginal zone lymphoma; small lymphocytic lymphoma or lymphoplasmacytic lymphoma) after treatment with at least 1 or more prior rituximab-containing regimens.
- Anti-CD20 mAb-refractory disease is defined as progressive disease while on rituximab (or another treatment of an anti-CD20 monoclonal antibody) or progression within 6 months of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
- Anti-CD20 mAb-sensitive disease is defined by a response to a prior rituximab-containing (or another treatment of an anti-CD20 monoclonal antibody) regimen, and relapse more than 6 months from the last administration of rituximab-containing (or another treatment of an anti-CD20 antibody-containing) therapy.
Measurable disease:
- At least one lymph node group ≥ 1.5 cm in longest transverse dimension. Patients with cutaneous only disease may be enrolled if they have a clearly measurable skin lesion.
- Relapsed or Refractory iNHL that has progressed during or following 1 or more prior systemic rituximab-containing (or another treatment of an anti-CD20 antibody-containing) regimens for lymphoma

PRIOR/CONCURRENT THERAPY:

No anti-lymphoma treatments within 28 days before the start of study treatment.
Must have recovered from side effects of prior treatments.

PATIENT CHARACTERISTICS:

Performance Status

• ECOG 0, 1, or 2

Renal Function • Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ≤ 1.5 X ULN

Bone Marrow Reserve

Platelets ≥30,000/uL
Hemoglobin ≥ 8g/dL
Absolute Lymphocytes ≥800/uL
ANC/AGC ≥750/uL

Hepatic Function

Total bilirubin ≤ 2.0 X ULN (unless Gilbert's Syndrome or disease infiltration of liver is present)
AST, ALT ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver lymphoma is present)
No positive Hep C serology or active Hep B infection

Cardiovascular

No congestive heart failure < 6 months
No unstable angina pectoris < 6 months
No myocardial infarction < 6 months
No history of ventricular arrhythmias or severe cardiac dysfunction
No history of uncontrollable supraventricular arrhythmias
No NYHA Class > II CHF
No marked baseline prolongation of QT/QTc interval

Pulmonary

• Normal clinical assessment of pulmonary function

Other

Negative serum pregnancy test if female and of childbearing potential
Women who are not pregnant or nursing
Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
No known autoimmune disease other than corrected hypothyroidism
No known prior organ allograft or allogeneic transplantation
Not HIV positive
No active CNS involvement with lymphoma
No psychiatric illness/social situation that would limit compliance
No other illness that in the opinion of the investigator would exclude the subject from participating in the study
Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
No active systemic infection requiring parenteral antibiotic therapy
No disease requiring systemic immunosuppressive therapy (inhaled or topical steroids are allowed). Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
No known histologic transformation from iNHL to DLBCL

Facility	Status	City	State	ZIP	Country	Contacts
University of Minnesota Cancer Center		Minneapolis	Minnesota	55455	United States
Washington University School of Medicine Oncology

PubMed Identifier	Type	Citation	Retractions
33832946	Derived	Foltz JA, Hess BT, Bachanova V, Bartlett NL, Berrien-Elliott MM, McClain E, Becker-Hapak M, Foster M, Schappe T, Kahl B, Mehta-Shah N, Cashen AF, Marin ND, McDaniels K, Moreno C, Mosior M, Gao F, Griffith OL, Griffith M, Wagner JA, Epperla N, Rock AD, Lee J, Petti AA, Soon-Shiong P, Fehniger TA. Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma. Clin Cancer Res. 2021 Jun 15;27(12):3339-3350. doi: 10.1158/1078-0432.CCR-20-4575. Epub 2021 Apr 8.

Label	URL
Related Info	View source

Arm/Group Information

ID	Title	Description
FG000	Phase 1 Cohort 1: N-803 - IV 1 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG001	Phase 1 Cohort 2: N-803 - IV 3 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG002	Phase 1 Cohort 3: N-803 - IV 6 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG003	Phase 1 Cohort 4: N-803 - SQ 6 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG004	Phase 1 Cohort 5: N-803 - SQ 10 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG005	Phase 1 Cohort 6: N-803 - SQ 15 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG006	Phase 1 Cohort 7: N-803 - SQ 20 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG007	Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
FG008	Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Phase 1 Cohort 1: N-803 - IV 1 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.
BG001	Phase 1 Cohort 2: N-803 - IV 3 ug/kg

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous		3 subjects from Phase 1 cohort 7 rolled over to the Phase 2 portion of the study. All other participants in Phase 2 only enrolled in the Phase 2 portion of the study.

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

MTD or MED of N-803: IV 1, 3, 6 μg/kg, SQ 6, 10, 15, 20 μg/kg

Maximum Tolerated Dose level (MTD) is defined as a dose level at which <2 out of 6 patients experienced Dose Limiting Toxicity (DLT) and that is one level below a dose that was not tolerated. Minimal Efficacious Dose (MED) is defined as a dose level which produces an Absolute Lymphocyte Count (ALC) ≥25,000/μL sustained for 14 days or a total WBC ≥35,000/μL sustained for 14 days among 2/3 or 4/6 of patients. The elevated ALC cannot be attributed to circulating lymphoma cells. Dose levels for N-803 1, 3, 6 μg/kg IV, and 6, 10, 15, 20 μg/kg subcutaneous (SQ) were used to determine the MTD or MED.

Posted

Number

SQ μg/kg

9 months

ID	Title	Description
OG000	Phase 1 Cohort 7: N-803 - SQ 20 μg/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Phase 1 Cohort 1: N-803 - IV 1 ug/kg	Rituximab: Intravenous infusion 375 mg/m^2. N-803: Intravenous infusion for Phase 1 cohort 1, 2 and 3; subcutaneous injection for Phase 1 cohort 4, 5, 6 and 7. Phase 2 dosing was based off of the MTD determined in Phase 1.

ID	Term
D012008	Recurrence
D008223	Lymphoma
D008228	Lymphoma, Non-Hodgkin
D009369	Neoplasms
D008224	Lymphoma, Follicular
D018442	Lymphoma, B-Cell, Marginal Zone
D015451	Leukemia, Lymphocytic, Chronic, B-Cell

ID	Term
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009370	Neoplasms by Histologic Type

ID	Term
D000069283	Rituximab
C582303	ALT-803

ID	Term
D058846	Antibodies, Monoclonal, Murine-Derived
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins