QUILT-3.002: N-803 in Patients With Relapse/Refractory iNHL in Conjunction With Rituximab

NCT02384954 | Terminated Phase 1 Results DMC

• 1 other identifier: CA-ALT-803-02-14
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

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.

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

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (9)

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

Biological: Rituximab; Biological: N-803

Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg

EXPERIMENTAL

Biological: Rituximab; Biological: N-803

Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg

EXPERIMENTAL

Biological: Rituximab; Biological: N-803

Interventions

Rituximab BIOLOGICAL

Intravenous infusion 375 mg/m\^2.

Also known as: Rituxin

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; Phase 1 Cohort 4: N-803 - SQ 6 ug/kg; Phase 1 Cohort 5: N-803 - SQ 10 ug/kg; Phase 1 Cohort 6: N-803 - SQ 15 ug/kg; Phase 1 Cohort 7: N-803 - SQ 20 ug/kg; Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg; Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg

N-803 BIOLOGICAL

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.

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; Phase 1 Cohort 4: N-803 - SQ 6 ug/kg; Phase 1 Cohort 5: N-803 - SQ 10 ug/kg; Phase 1 Cohort 6: N-803 - SQ 15 ug/kg; Phase 1 Cohort 7: N-803 - SQ 20 ug/kg; Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg; Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Altor BioScience: lead

Study Sites (4)

University of Minnesota Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine Oncology

St Louis, Missouri, 63110, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (1)

• 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.

  PMID: 33832946 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Recurrence; Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximab; ALT-803

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@Immunitybio.com

855-797-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 19, 2015
• First Posted: March 10, 2015
• Study Start: April 17, 2015
• Primary Completion: December 13, 2020
• Study Completion: December 13, 2020
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2024-07

Locations

US (4)