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

February 11, 2021 updated by: Altor BioScience

A Phase 1/2 Study of ALT-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Cancer Center
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine Oncology
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I/II ALT-803 w/rituximab for rel/ref iNHL
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
9 months
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.
36 months
Overall Response Rate
Time Frame: 60 months

For Phase 1 and 2

Complete response plus partial response of treated patients
60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
60 months
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).
60 months
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).
60 months
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.
36 months
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.
36 Months
Immunogenicity
Time Frame: 36 Months

For Phase 1 and 2

Measure the level of anti-ALT-803 neutralizing effects in each patient
36 Months
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.
36 Months
Polymorphism
Time Frame: 36 Months

For Phase 1 and 2

Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes.
36 Months
Mutations
Time Frame: 36 Months

For Phase 1 and 2

Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes.
36 Months
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.
36 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Altor BioScience

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2015

Primary Completion (Actual)

December 31, 2020

Study Completion (Actual)

December 31, 2020

Study Registration Dates

First Submitted

February 19, 2015

First Submitted That Met QC Criteria

March 4, 2015

First Posted (Estimate)

March 10, 2015

Study Record Updates

Last Update Posted (Actual)

February 15, 2021

Last Update Submitted That Met QC Criteria

February 11, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA-ALT-803-02-14

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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