QUILT-3.002: ALT-803 in Patients With Relapse/Refractory iNHL in Conjunction With Rituximab
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
| 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:
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.
|
Outcome Measures
Primary Outcome Measures
- Determination of MTD or MED, Phase II Dose Level Designation [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 [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 [60 months]
For Phase 1 and 2 Complete response plus partial response of treated patients
Secondary Outcome Measures
- Progression-free Survival [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 [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 [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 [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 [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 [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 [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 [36 Months]
For Phase 1 and 2 Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes.
- Mutations [36 Months]
For Phase 1 and 2 Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes.
- Lymph node biopsies [36 Months]
For Phase 1 and 2 Determine the impact of study treatment on the immune cell composition within the tumor microenvironment.
Eligibility Criteria
Criteria
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.
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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.
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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.
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Measurable disease:
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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.
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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:
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No anti-lymphoma treatments within 28 days before the start of study treatment.
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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
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Hemoglobin ≥ 8g/dL
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Absolute Lymphocytes ≥800/uL
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ANC/AGC ≥750/uL
Hepatic Function
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Total bilirubin ≤ 2.0 X ULN (unless Gilbert's Syndrome or disease infiltration of liver is present)
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AST, ALT ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver lymphoma is present)
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No positive Hep C serology or active Hep B infection
Cardiovascular
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No congestive heart failure < 6 months
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No unstable angina pectoris < 6 months
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No myocardial infarction < 6 months
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No history of ventricular arrhythmias or severe cardiac dysfunction
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No history of uncontrollable supraventricular arrhythmias
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No NYHA Class > II CHF
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No marked baseline prolongation of QT/QTc interval
Pulmonary
• Normal clinical assessment of pulmonary function
Other
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Negative serum pregnancy test if female and of childbearing potential
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Women who are not pregnant or nursing
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Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
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No known autoimmune disease other than corrected hypothyroidism
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No known prior organ allograft or allogeneic transplantation
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Not HIV positive
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No active CNS involvement with lymphoma
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No psychiatric illness/social situation that would limit compliance
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No other illness that in the opinion of the investigator would exclude the subject from participating in the study
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Must provide informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations
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No active systemic infection requiring parenteral antibiotic therapy
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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.
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No known histologic transformation from iNHL to DLBCL
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Minnesota Cancer Center | Minneapolis | Minnesota | United States | 55455 |
| 2 | Washington University School of Medicine Oncology | Saint Louis | Missouri | United States | 63110 |
| 3 | The Ohio State University | Columbus | Ohio | United States | 43210 |
| 4 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
Sponsors and Collaborators
- Altor BioScience
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CA-ALT-803-02-14