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

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ClinicalTrials.gov Identifier: NCT02384954
Recruitment Status : Terminated (Change in drug product development strategy.)
First Posted : March 10, 2015
Last Update Posted : February 15, 2021
Sponsor:
Information provided by (Responsible Party):
Altor BioScience

Tracking Information
First Submitted Date  ICMJE February 19, 2015
First Posted Date  ICMJE March 10, 2015
Last Update Posted Date February 15, 2021
Actual Study Start Date  ICMJE April 2015
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2015)
  • Determination of MTD or MED, Phase II Dose Level Designation [ Time Frame: 9 months ]
    For Phase I Determine the maximum tolerated dose (MTD) level or minimum efficacious dose (MED) and designate the dose level for phase II.
  • Number of treatment related adverse events as a measure of safety [ Time Frame: 36 months ]
    For Phase 1 and 2 Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment will be collected.
  • Overall Response Rate [ Time Frame: 60 months ]
    For Phase 1 and 2 Complete response plus partial response of treated patients
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 14, 2017)
  • Progression-free Survival [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Overall Survival [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Duration of Response [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Blood Cell Counts [ Time Frame: 36 months ]
    For Phase 1 and 2 Evaluation of the effect of ALT-803 on the peripheral ALC and WBC counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells in treated patients.
  • Levels of specific biomarkers as a predictive measure of efficacy [ Time Frame: 36 Months ]
    For Phase 1 and 2 Measures the serum levels of including but not limited to IL-2, IL-4, IL-6, IL-10, IFN-gamma, MCP-1 and TNF-alpha in treated patients.
  • Immunogenicity [ Time Frame: 36 Months ]
    For Phase 1 and 2 Measure the level of anti-ALT-803 neutralizing effects in each patient
  • Pharmacokinetics as a measure of drug persistence [ Time Frame: 36 Months ]
    For Phase 1 and 2 Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803 collected from treated patients.
  • Polymorphism [ Time Frame: 36 Months ]
    For Phase 1 and 2 Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes.
  • Mutations [ Time Frame: 36 Months ]
    For Phase 1 and 2 Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes.
  • Lymph node biopsies [ Time Frame: 36 Months ]
    For Phase 1 and 2 Determine the impact of study treatment on the immune cell composition within the tumor microenvironment.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2015)
  • Progression-free Survival [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Overall Survival [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Duration of Response [ Time Frame: 60 months ]
    For Phase 1 and 2 Of all treated patients will be assessed at least every three months during years 1 and 2, every 4 months during year 3, and then every 6 months (+/- 2 months) during years 4 and 5 from the start of study treatment, or through the point designated as the end of the study follow up (5 years).
  • Blood Cell Counts [ Time Frame: 36 months ]
    For Phase 1 and 2 Evaluation of the effect of ALT-803 on the peripheral ALC and WBC counts, the number and phenotype of peripheral blood T (total and subsets) and NK cells in treated patients.
  • Levels of specific biomarkers as a predictive measure of efficacy [ Time Frame: 36 Months ]
    For Phase 1 and 2 Measures the serum levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha in treated patients.
  • Immunogenicity [ Time Frame: 36 Months ]
    For Phase 1 and 2 Measure the level of anti-ALT-803 neutralizing effects in each patient
  • Pharmacokinetics as a measure of drug persistence [ Time Frame: 36 Months ]
    For Phase 1 and 2 Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803 collected from treated patients.
  • Polymorphism [ Time Frame: 36 Months ]
    For Phase I and 2 Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes.
  • Mutations [ Time Frame: 36 Months ]
    For Phase I and 2 Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE QUILT-3.002: ALT-803 in Patients With Relapse/Refractory iNHL in Conjunction With Rituximab
Official Title  ICMJE A Phase 1/2 Study of ALT-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab
Brief Summary This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of ALT-803 in patients with relapse/refractory indolent B cell non-Hodgkin lymphoma in conjunction with rituximab.
Detailed Description

The purpose of this study is to evaluate the safety and tolerability, identify the Maximum Tolerated Dose (MTD) or the Minimum Efficacious Dose (MED) and designate a dose level for Phase 2. Also characterize the immunogenicity, pharmacokinetic profile, and biomarker serum levels of ALT-803 in treated patients.

The effect of ALT-803 on the peripheral absolute lymphocyte counts and white blood cell counts, the number, phenotype and repertoire of peripheral blood T (total and subsets) and NK cells will be evaluated. In addition, a subset of patients will be evaluated for changes in lymph node immune composition. Anti-tumor responses and survival data will also be collected in this trial.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma
Intervention  ICMJE
  • Biological: Rituximab
    Intravenous infusion; Patients will receive a 4-week induction cycle consisting of Rituximab given on Day 1, 8, 15, 22. Eligible patients will receive a consolidation treatment consisting of Rituximab given on Day 78, 134, 190, 246.
    Other Name: Rituxin
  • Biological: ALT-803
    Intravenous infusion for cohort 1, 2 and 3; subcutaneous injection for cohort 4, 5, 6 and 7; Patients will receive a 4-week induction cycle consisting of ALT-803 given on Day 2, 8, 15, 22 for patients in cohort 1, 2, 3, 4 and Day 1, 8, 15 and 22 for patients in cohort 5, 6, 7. Eligible patients will receive a consolidation treatment consisting of ALT-803 given on Day 78, 134, 190, 246.
Study Arms  ICMJE Experimental: Phase I/II ALT-803 w/rituximab for rel/ref iNHL
Interventions:
  • Biological: Rituximab
  • Biological: ALT-803
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: February 11, 2021)
43
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2015)
75
Actual Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02384954
Other Study ID Numbers  ICMJE CA-ALT-803-02-14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Altor BioScience
Study Sponsor  ICMJE Altor BioScience
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Altor BioScience
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP