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

NCT02099539 | Terminated Phase 1 Results DMC

• 2 other identifiers: CA-ALT-803-02-13CA167925
• Study Type: interventional
• Target: 19
• 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 relapsed or refractory multiple myeloma.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (9)

• Characterization of the Pharmacokinetic Profile - Half-life (t½)

  PK timepoint up to 72 hours +/- 6 hours

• Characterization of the Pharmacokinetic Profile - Time of the Observed Maximum Concentration (Tmax)

  PK timepoint up to 72 hours +/- 6 hours

• Characterization of the Pharmacokinetic Profile - Maximum Observed Concentration (Cmax)

  PK timepoint up to 72 hours +/- 6 hours

• Characterization of the Pharmacokinetic Profile - Area Under the Plasma Concentration Curve

  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)

  PK timepoint up to 72 hours +/- 6 hours

Study Arms (6)

Cohort 1: N-803 - IV 1 ug/kg

EXPERIMENTAL

Biological: N-803

Cohort 2: N-803 - IV 3 ug/kg

EXPERIMENTAL

Biological: N-803

Cohort 3: N-803 - IV 6 ug/kg

EXPERIMENTAL

Biological: N-803

Cohort 4: N-803 - IV 10 ug/kg

EXPERIMENTAL

Biological: N-803

Cohort 5: N-803 - SQ 10 ug/kg

EXPERIMENTAL

Biological: N-803

Cohort 6: N-803 - SQ 15 ug/kg

EXPERIMENTAL

Biological: N-803

Interventions

N-803 BIOLOGICAL

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

Cohort 1: N-803 - IV 1 ug/kg; Cohort 2: N-803 - IV 3 ug/kg; Cohort 3: N-803 - IV 6 ug/kg; Cohort 4: N-803 - IV 10 ug/kg; Cohort 5: N-803 - SQ 10 ug/kg; Cohort 6: N-803 - SQ 15 ug/kg

Eligibility Criteria

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

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.

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

Sponsors & Collaborators

• Altor BioScience: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Recurrence; Multiple Myeloma; Neoplasms

Interventions

ALT-803

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

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

Bobby.Reddy@Immunitybio.com

855-797-9277

Study Officials

• Hing C Wong, PhD

  Altor BioScience

  STUDY CHAIR

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 26, 2014
• First Posted: March 31, 2014
• Study Start: October 6, 2014
• Primary Completion: June 19, 2018
• Study Completion: June 19, 2018
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2018-01

Locations

US (4)