Clinical trial NCT02099539: QUILT-3.005: A Study of N-803 in Patients With Relapsed or Refractory Multiple Myeloma
Official title: A Phase I/II Study of N-803 in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: absolute lymphocyte count
antitumor
cancer
immunotherapy
immunochemotherapy
interleukin-15
multiple myeloma
NK cell
refractory
relapsed
T cell
white blood cell count
Lead sponsor: Altor BioScience
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2014-03-31
Enrollment: 19
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 relapsed or refractory multiple myeloma.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: 24 weeks
measure: Disease Response Rate of Treated Patients
timeFrame: Starts at Week 11 - 12 and Week 23 - 24
Secondary outcomes:
measure: Characterization of the Pharmacokinetic Profile - Half-life (t½)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve
timeFrame: 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.
measure: Characterization of the Pharmacokinetic Profile - Clearance (CL)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Characterization of the Pharmacokinetic Profile - Vss Volume of Distribution at Steady State
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Immunogenicity - Anti-drug Antibody (ADA)
timeFrame: From Baseline up to Week 12
measure: Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Clearance (CL/F)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
measure: Characterization of the Pharmacokinetic Profile - Apparent (Extravascular) Volume of Distribution (Vz/F)
timeFrame: PK timepoint up to 72 hours +/- 6 hours
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Cancer Center
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: Altor BioScience
name: Hing C Wong, PhD
role: STUDY_CHAIR
References: