Clinical trial NCT02384954: QUILT-3.002: N-803 in Patients With Relapse/Refractory iNHL in Conjunction With Rituximab
Official title: A Phase 1/2 Study of N-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma
Keywords: Lymphoma
indolent B Cell
non-Hodgkin Lymphoma
Cancer
Immunotherapy
Relapsed
Refractory
Rituximab
Interleukin-15
Absolute Lymphocyte Count
White Blood Cell
Follicular Lymphoma
Marginal Zone Lymphoma
Small Lymphocytic Lymphoma
Lymphoplasmacytic Lymphoma
anti-CD20
Lead sponsor: Altor BioScience
Sponsor class: INDUSTRY
First posted: 2015-03-10
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of N-803 in patients with relapse/refractory indolent B cell non-Hodgkin lymphoma in conjunction with rituximab.

Detailed description: The purpose of this study is to evaluate the safety and tolerability, identify the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and designate a dose level for Phase 2. Also characterize the immunogenicity, pharmacokinetic profile, and biomarker serum levels of N-803 in treated patients.

The effect of N-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number, phenotype and repertoire of peripheral blood T (total and subsets) and NK cells will be evaluated. In addition, a subset of patients will be evaluated for changes in lymph node immune composition. Anti-tumor responses and survival data will also be collected in this trial.

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

Primary outcomes:
measure: MTD or MED of N-803: IV 1, 3, 6 μg/kg, SQ 6, 10, 15, 20 μg/kg
timeFrame: 9 months
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 30 days after last dose, up to 40 weeks
measure: Overall Response Rate
timeFrame: 60 months
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine Oncology
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
References:
citation: 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.