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NCT02384954

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

Terminated Phase 1, PHASE2 Results posted Last updated 3 July 2024
What this trial tests

Phase 1, PHASE2 trial testing Rituximab in Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma in 43 participants. Terminated before completion.

Timeline
17 April 2015
Primary endpoint
13 December 2020
13 December 2020

Quick facts

Lead sponsorAltor BioScience
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment43
Start date17 April 2015
Primary completion13 December 2020
Estimated completion13 December 2020
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Altor BioScience — full company profile →

Who can join

18 and older, any sex, with Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

MTD or MED of N-803: IV 1, 3, 6 μg/kg, SQ 6, 10, 15, 20 μg/kg Primary · 9 months

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

GroupValue95% CI
Phase 1 Cohort 7: N-803 - SQ 20 μg/kg20
Number of Participants With Treatment Emergent Adverse Events Primary · 30 days after last dose, up to 40 weeks

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.

Phase 1
GroupValue95% CI
Phase 1 Cohort 1: N-803 - IV 1 ug/kg3
Phase 1 Cohort 2: N-803 - IV 3 ug/kg3
Phase 1 Cohort 3: N-803 - IV 6 ug/kg3
Phase 1 Cohort 4: N-803 - SQ 6 ug/kg3
Phase 1 Cohort 5: N-803 - SQ 10 ug/kg3
Phase 1 Cohort 6: N-803 - SQ 15 ug/kg3
Phase 1 Cohort 7: N-803 - SQ 20 ug/kg3
Phase 2
GroupValue95% CI
Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg16
Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg9
Overall Response Rate Primary · 60 months

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.

Phase 1
GroupValue95% CI
Phase 1 Cohort 1: N-803 - IV 1 ug/kg330.8 – 90.6
Phase 1 Cohort 2: N-803 - IV 3 ug/kg330.8 – 90.6
Phase 1 Cohort 3: N-803 - IV 6 ug/kg679.4 – 99.2
Phase 1 Cohort 4: N-803 - SQ 6 ug/kg330.8 – 90.6
Phase 1 Cohort 5: N-803 - SQ 10 ug/kg679.4 – 99.2
Phase 1 Cohort 6: N-803 - SQ 15 ug/kg679.4 – 99.2
Phase 1 Cohort 7: N-803 - SQ 20 ug/kg10029.2 – 100
Phase 2
GroupValue95% CI
Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg8051.9 – 95.7
Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg337.5 – 70.1

Adverse events — posted to ClinicalTrials.gov

Time frame: All AEs and SAEs were to be reported within 30 days of the last dose of study treatment, regardless of attribution, up to 40 weeks. All deaths were followed during the disease progression and survival follow-up period, up to 42 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1 Cohort 1: N-803 - IV 1 ug/kg
Serious: 0/3 (0%)
Deaths: 0/3
Phase 1 Cohort 2: N-803 - IV 3 ug/kg
Serious: 0/3 (0%)
Deaths: 0/3
Phase 1 Cohort 3: N-803 - IV 6 ug/kg
Serious: 1/3 (33%)
Deaths: 0/3
Phase 1 Cohort 4: N-803 - SQ 6 ug/kg
Serious: 1/3 (33%)
Deaths: 0/3
Phase 1 Cohort 5: N-803 - SQ 10 ug/kg
Serious: 0/3 (0%)
Deaths: 0/3
Phase 1 Cohort 6: N-803 - SQ 15 ug/kg
Serious: 0/3 (0%)
Deaths: 0/3
Phase 1 Cohort 7: N-803 - SQ 20 ug/kg
Serious: 1/3 (33%)
Deaths: 0/3
Phase 2 Cohort 1: Anti-CD20 mAb-sensitive N-803 - SQ 20 ug/kg
Serious: 3/16 (19%)
Deaths: 0/16
Phase 2 Cohort 2: Anti-CD20 mAb-refractory N-803 - SQ 20 ug/kg
Serious: 2/9 (22%)
Deaths: 0/9

Serious adverse events (9 terms)

ReactionSystemPhase 1 Cohort 1: N-803 - …Phase 1 Cohort 2: N-803 - …Phase 1 Cohort 3: N-803 - …Phase 1 Cohort 4: N-803 - …Phase 1 Cohort 5: N-803 - …Phase 1 Cohort 6: N-803 - …Phase 1 Cohort 7: N-803 - …Phase 2 Cohort 1: Anti-CD2…Phase 2 Cohort 2: Anti-CD2…
Small intestinal obstructionGastrointestinal disorders
Cerebrovascular accidentNervous system disorders
Urinary tract infectionInfections and infestations
Acute respiratory distress syndromeRespiratory, thoracic and mediastinal disorders
Sinus node dysfunctionCardiac disorders
AscitesGastrointestinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Other adverse events (150 terms — click to expand)

ReactionSystemPhase 1 Cohort 1: N-803 - …Phase 1 Cohort 2: N-803 - …Phase 1 Cohort 3: N-803 - …Phase 1 Cohort 4: N-803 - …Phase 1 Cohort 5: N-803 - …Phase 1 Cohort 6: N-803 - …Phase 1 Cohort 7: N-803 - …Phase 2 Cohort 1: Anti-CD2…Phase 2 Cohort 2: Anti-CD2…
Injection site reactionGeneral disorders
PyrexiaGeneral disorders
ChillsGeneral disorders
FatigueGeneral disorders
Infusion related reactionInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
PainGeneral disorders
HeadacheNervous system disorders
Abdominal distensionGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
VomitingGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Night sweatsSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
StomatitisGastrointestinal disorders
Localised oedemaGeneral disorders
MalaiseGeneral disorders
Oedema peripheralGeneral disorders
SinusitisInfections and infestations
Urinary tract infectionInfections and infestations
DizzinessNervous system disorders
Alanine aminotransferase increasedInvestigations
Blood alkaline phosphatase increasedInvestigations
Lymphocyte count decreasedInvestigations
Neutrophil count decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
Lymph node painBlood and lymphatic system disorders
DepressionPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
HypertensionVascular disorders
HypotensionVascular disorders
AnaemiaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders

Most-reported serious reactions: Small intestinal obstruction, Cerebrovascular accident, Urinary tract infection, Acute respiratory distress syndrome, Sinus node dysfunction, Ascites, Pleural effusion, Neutropenia.

Data from ClinicalTrials.gov NCT02384954 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Exploring the NK cell platform for cancer immunotherapy.
    Myers JA, Miller JS. · · 2021 · cited 977× · PMID 32934330 · DOI 10.1038/s41571-020-0426-7
  2. Cytokines in clinical cancer immunotherapy.
    Berraondo P, Sanmamed MF, Ochoa MC, Etxeberria I, et al · · 2019 · cited 834× · PMID 30413827 · DOI 10.1038/s41416-018-0328-y
  3. NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity in Cancer Immunotherapy.
    Wang W, Erbe AK, Hank JA, Morris ZS, et al · · 2015 · cited 421× · PMID 26284063 · DOI 10.3389/fimmu.2015.00368
  4. The NK cell-cancer cycle: advances and new challenges in NK cell-based immunotherapies.
    Bald T, Krummel MF, Smyth MJ, Barry KC. · · 2020 · cited 388× · PMID 32690952 · DOI 10.1038/s41590-020-0728-z
  5. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation.
    Romee R, Cooley S, Berrien-Elliott MM, Westervelt P, et al · · 2018 · cited 318× · PMID 29463563 · DOI 10.1182/blood-2017-12-823757
  6. Cancer Immunotherapy Based on Natural Killer Cells: Current Progress and New Opportunities.
    Hu W, Wang G, Huang D, Sui M, et al · · 2019 · cited 279× · PMID 31214177 · DOI 10.3389/fimmu.2019.01205
  7. Continuous treatment with IL-15 exhausts human NK cells via a metabolic defect.
    Felices M, Lenvik AJ, McElmurry R, Chu S, et al · · 2018 · cited 210× · PMID 29415897 · DOI 10.1172/jci.insight.96219
  8. Harnessing IL-15 signaling to potentiate NK cell-mediated cancer immunotherapy.
    Ma S, Caligiuri MA, Yu J. · · 2022 · cited 163× · PMID 36058806 · DOI 10.1016/j.it.2022.08.004

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