QUILT-3.005: A Study of N-803 in Patients With Relapsed or Refractory Multiple Myeloma

A Phase I/II Study of N-803 in Patients With Relapsed or Refractory Multiple Myeloma

This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of N-803 in patients with relapsed or refractory multiple myeloma.

Study Overview

• Status: Terminated
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Biological: N-803

Detailed Description

The purpose of this study is to evaluate the safety, determine the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and characterize the immunogenicity and pharmacokinetic profile of N-803 in treated patients. The effect of N-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells will be evaluated. The anti-tumor responses of N-803 will also be assessed in this trial.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at least two different previous regimens.

  • Refractory disease is defined as progressive disease while on therapy or progression within 60 days of therapy.
  • Progressive disease is defined by a 25% increase from the lowest response value in specified tests.

• Measurable disease as defined by at least one of the following:

  • Serum M-protein ≥ 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA)
  • Urine M-protein ≥ 200mg/24hours
  • Serum free light chains ≥ 10 mg/dL and abnormal kappa/lambda ratio

PRIOR/CONCURRENT THERAPY:

• No anti-myeloma treatments within 14 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

Bone Marrow Reserve

• Absolute neutrophil count (AGC/ANC) ≥ 1000/uL
• Platelets ≥ 30,000/uL
• Hemoglobin ≥ 8g/dL
• Absolute lymphocytes ≥ 800/uL
• Leukocytes ≥ 3,000/uL

Renal Function

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

Hepatic Function

• Total bilirubin ≤ 2.0 X ULN
• AST, ALT, ALP ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver metastases exist)
• 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
• No history of 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 history or evidence of uncontrollable CNS disease
• No psychiatric illness/social situation
• 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 on-going chronic systemic corticosteroid (>10 mg daily prednisone equivalent) use or other immunosuppressive therapy (a history of mild asthma not requiring therapy is eligible). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: N-803 - IV 1 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Experimental: Cohort 2: N-803 - IV 3 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Experimental: Cohort 3: N-803 - IV 6 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Experimental: Cohort 4: N-803 - IV 10 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Experimental: Cohort 5: N-803 - SQ 10 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles
Experimental: Cohort 6: N-803 - SQ 15 ug/kg	Biological: N-803; Intravenous infusion for cohort 1, 2, 3 and 4; subcutaneous injection for cohort 5, 6 and 7; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events	For phase I - Number of Participants with Treatment Emergent Adverse Events that occur or worsen after the first dose of study treatment.	24 weeks
Disease Response Rate of Treated Patients	CR- negative SIFE and UIFE, disappearance of any soft tissue plasmacytomas, and < or = to 5% plasma cells in bone marrow VGPR - either + SIFE and UIFE and - SPEP and UPEP or reduction in serum M-protein > or = to 90% and urine m-protein level <100mg per 24h PR - if measurable serum an urine m-protein them reduction of serum m-protein by >=50% and reduction in 24h urinary m protein by >=90% or to <200mg per 24h if unmeasurable serum and urine m-protein then >= 50% decrease in the difference between involve and uninvolved FLC levels If unmeasurable serum and urine m-protein and serum FLC assay then >= 50% reduction in plasma cells, provide baseline bone marrow plasma cell percentage was >=30% In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size of soft tissue plasmacytomas is also required PD - defined via International Myeloma Working Group uniform response criteria: disease progression SD - not meeting criteria for CR, VGPR, PR or PD	Starts at Week 11 - 12 and Week 23 - 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterization of the Pharmacokinetic Profile - Half-life (t½)	Half-life (t½) - The period of time required for the concentration or amount of drug in the body to be reduced by one-half.	PK timepoint up to 72 hours +/- 6 hours
Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax)	time of the observed maximum concentration (Tmax)	PK timepoint up to 72 hours +/- 6 hours
Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax)	maximum observed concentration (Cmax)	PK timepoint up to 72 hours +/- 6 hours
Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve	Area under the plasma concentration curve from time 0 through the last measurable concentration (AUC0-t). PK samples were obtained from the start of treatment until 72 hours. The AUC0-168 and AUC0-inf were calculated with noncompartmental pharmacokinetic analysis equations.	Samples were collected and the AUC was determined at 24 hours and at time t (last measurable concentration). The AUC was calculated for 168 hours and time to infinity.
Characterization of the Pharmacokinetic Profile - Clearance (CL)	Clearance (CL)	PK timepoint up to 72 hours +/- 6 hours
Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State	Vss Volume of distribution at steady state is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration	PK timepoint up to 72 hours +/- 6 hours
Immunogenicity - Anti-drug Antibody (ADA)	Number of patients with a positive Anti-drug Antibody (ADA) result	From Baseline up to Week 12
Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Clearance (CL/F)	Apparent (Extravascular) Clearance (CL/F)	PK timepoint up to 72 hours +/- 6 hours
Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Volume of Distribution (Vz/F)	Apparent volume of distribution is a ratio of the total amount of drug in the body to the plasma concentration of the drugs such that Vd = amount of drug in body/plasma drug concentration	PK timepoint up to 72 hours +/- 6 hours

Collaborators and Investigators

• Sponsor: Altor BioScience
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Hing C Wong, PhD, Altor BioScience

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2014
• Primary Completion (Actual): June 19, 2018
• Study Completion (Actual): June 19, 2018

Study Registration Dates

• First Submitted: February 26, 2014
• First Submitted That Met QC Criteria: March 26, 2014
• First Posted (Estimated): March 31, 2014

Study Record Updates

• Last Update Posted (Actual): September 26, 2024
• Last Update Submitted That Met QC Criteria: September 20, 2024
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; immunochemotherapy; antitumor; relapsed; refractory; T cell; absolute lymphocyte count; interleukin-15; multiple myeloma; NK cell; white blood cell count
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CA-ALT-803-02-13; CA167925 (Other Identifier: NIH)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No