Relapsed/Refractory Indolent B Cell Non-Hodgkin Lymphoma Clinical Trial
Official title:
A Phase 1/2 Study of ALT-803 in Patients With Relapse/Refractory Indolent B Cell Non-Hodgkin Lymphoma in Conjunction With Rituximab
| Verified date | February 2021 |
| Source | Altor BioScience |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Terminated |
| Enrollment | 43 |
| Est. completion date | December 31, 2020 |
| Est. primary completion date | December 31, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | The Ohio State University | Columbus | Ohio |
| United States | University of Minnesota Cancer Center | Minneapolis | Minnesota |
| United States | Washington University School of Medicine Oncology | Saint Louis | Missouri |
| Lead Sponsor | Collaborator |
|---|---|
| Altor BioScience |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Determination of MTD or MED, Phase II Dose Level Designation | 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 | |
| Primary | Number of treatment related adverse events as a measure of safety | 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 | |
| Primary | Overall Response Rate | For Phase 1 and 2
Complete response plus partial response of treated patients |
60 months | |
| Secondary | Progression-free Survival | 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 | |
| Secondary | Overall Survival | 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 | |
| Secondary | Duration of Response | 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 | |
| Secondary | Blood Cell Counts | 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 | |
| Secondary | Levels of specific biomarkers as a predictive measure of efficacy | 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 | |
| Secondary | Immunogenicity | For Phase 1 and 2
Measure the level of anti-ALT-803 neutralizing effects in each patient |
36 Months | |
| Secondary | Pharmacokinetics as a measure of drug persistence | 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 | |
| Secondary | Polymorphism | For Phase 1 and 2
Determine the fcgr3a polymorphism status in each patient to correlate with clinical outcomes. |
36 Months | |
| Secondary | Mutations | For Phase 1 and 2
Test the recurrent lymphoma mutations in each patient to correlate with clinical outcomes. |
36 Months | |
| Secondary | Lymph node biopsies | For Phase 1 and 2
Determine the impact of study treatment on the immune cell composition within the tumor microenvironment. |
36 Months |