Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL

Study Overview
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Brief Summary
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This is an open-label extension study enrolling participants experiencing clinical benefit following 6 cycles of DI-Leu16-IL2 while enrolled in the Alopexx Oncology Dose-Escalation AO-101 study (NCT01874288). Participants will be permitted to continue to receive DI-Leu16-IL2 at the same dose, schedule, and route of administration they received during Study AO-101 (Main Study). Prior pre-treatment (for example, Rituximab) will continue as before.

Official Title
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An Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Patients With B-cell Non-Hodgkin Lymphoma (NHL)

Conditions
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B-cell Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: DI-Leu16-IL2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants currently entered on Alopexx Oncology Study AO-101 Participants who received 6 cycles of DI-Leu16-IL2 on Study AO-101. Documented clinical benefit following 6th cycle of DI-Leu16-IL2 Able to begin extension study within 8 weeks of receiving 6th cycle of DI-Leu16-IL2 Participants must have received prior Rituximab-containing therapy. Participants in this extension study are to use adequate birth control measures (abstinence, oral contraceptives, barrier method with spermicide or surgical sterilization) during the study. Females of childbearing potential must have a negative serum pregnancy test on the days of dosing. A female of childbearing potential: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (that is, has had menses at any time in the preceding 24 consecutive months. Provide written informed consent prior to any study procedures. Exclusion Criteria: Pregnant or lactating female An immediate need for palliative radiotherapy or systemic corticosteroid therapy. Actively infected with or chronic carriers of hepatitis B virus (HBV) as demonstrated by positive hepatitis B core antibody (HbcAb) or hepatitis B surface antigen (HbsAg). Participants who are sero-positive only, that is, surface antibody positive [HbsAb], are permitted. Other significant active infection Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1 Uncontrolled hypertension (diastolic ≥ 100 millimeters of mercury [mmHg]) or hypotension (systolic ≤ 90 mmHg) History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DI-Leu16-IL2 1.0 mg/m^2<br>Participants will receive DI-Leu16-IL2 1.0 milligrams per square meter (mg/m^2) subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle). Participants will continue to receive therapy through the duration of the study as long as they will have clinical benefit and will not experience any untoward side effects. | Drug: DI-Leu16-IL2<br>* DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.<br>|
| Experimental: DI-Leu16-IL2 2.0 mg/m^2<br>Participants will receive DI-Leu16-IL2 2.0 mg/m^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants will continue to receive therapy through the duration of the study as long as they will have clinical benefit and will not experience any untoward side effects. | Drug: DI-Leu16-IL2<br>* DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria | BOR included complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD), and progressive disease (PD). CR: 1)Disappearance of all detectable clinical and radiological evidence of disease; 2)lymph nodes (LN) regressed to normal size; 3)other organs (spleen, liver, kidneys) that were enlarged before therapy must have decreased in size; 4)clear bone marrow(BM) infiltrate. CRu: must meet CR criteria 1 and 3, as well as ≥1 of following: residual LN mass >1.5 centimeters (cm) in greatest transverse diameter; individual nodes that were previously confluent regressed by >75% in sum of product diameters (SPD); or indeterminate BM. PR: 6 largest dominant nodes or nodal masses decreased by ≤50% in SPD; no increase in size of other nodes; liver or spleen; splenic and hepatic nodules regressed ≥50% in SPD; and no new disease. SD: less than a PR but not PD. PD: 50% increase from nadir in SPD of any abnormal node for PR or nonresponders and appearance of any new lesion. | First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months) | 
| Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study | Sum of product diameters sums the product of the 2 tumor measurements on each lesion. If only 1 measurement was available, it was used as the longest length and the product of the lengths in the sum. Baseline value is the last non-missing measurement prior to receiving study drug injection in the Main Study AO-101. | Baseline, end of study (EOS) (up to approximately 32 months) | 
| Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study | Sum of longest diameters is the sum of the longest measured length of each tumor lesion. Baseline value is the last non-missing measurement prior to receiving study drug injection in the Main Study AO-101. None of the participants were considered evaluable in 'DI-Leu16-IL2 2.0 mg/m^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm | Baseline, EOS (up to approximately 32 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAEs were defined as AEs with onset at the time of or following the start of treatment with study drug, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. | First dose of study drug up to EOS (up to 20 months) | 
| Number of Participants With a TEAE That Was Considered Related to a Clinically Significant Hematology or Serum Chemistry Abnormality | TEAEs were defined as AEs with onset at the time of or following the start of treatment with study drug, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Clinically significant hematology and serum chemistry abnormalities were identified at the Investigator's discretion. | First dose of study drug up to EOS (up to 20 months) | 
| Number of Participants With a Clinically Significant Abnormal Physical Exam | Clinically significant abnormal physical exams included extremities, head, ears, eyes, nose, throat, abdomen, respiratory system, lymphatic system, and integumentary system. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section. Clinically significant abnormal physical exams were identified at the Investigator's discretion. | First dose of study drug up to EOS (up to 20 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)