Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

B-cell Lymphoma

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.

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.

DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.

DI-Leu16-IL2

Daniel Vlock, MD

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.

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

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

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.

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.

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

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.

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.

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.

Alopexx Oncology, LLC

Safety population included all enrolled participants who received at least 1 dose of study drug.

Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.

DI-Leu16-IL2 1.0 mg/m^2

Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle). Participants continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.

DI-Leu16-IL2 2.0 mg/m^2

Total

Age, Categorical

Sex: Female, Male

Clinical benefit was noted before the scheduled completion of the trial, hence; the study was terminated early.

Chief Medical Officer

Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria

Safety population included all enrolled participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. 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.

Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study

Safety population included all enrolled participants who received at least 1 dose of study drug. Here, 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study

Any TEAEs

SAEs

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Number of Participants With a TEAE That Was Considered Related to a Clinically Significant Hematology or Serum Chemistry Abnormality

Number of Participants With a Clinically Significant Abnormal Physical Exam

Participants received 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 continued to receive therapy through the duration of the study as long as they were having clinical benefit and not experiencing any untoward side effects.

Overall Study

Participants will receive DI-Leu16-IL2 0.5 mg/m\^2 subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Participants will receive DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Participants will receive DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Participants will receive DI-Leu16-IL2 4.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles

Participants will receive DI-Leu16-IL2 6.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

This dose-escalation study is designed for determining the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to participants with cluster of differentiation 20 (CD20) positive NHL that have failed standard rituximab-containing therapy.

The participants will be enrolled during dose escalation and during 2 expansion cohorts of up to 12 participants each.

The dose escalation portion of the trial will incorporate a modified accelerated titration design. Therefore, the trial will enroll 3 participants per dose level with a doubling of the dose at each level during the accelerated stage of the study (skipping every other dose level). Once the first instance of any Grade 3 or higher treatment related toxicity (with some notable exceptions) is observed on the first cycle, the accelerated stage will end and the trial will revert to a conventional design using cohorts of 3 or 6 participants (standard 3+3 design), with single step 2 milligrams (mg)/square meter (m\^2) increments.

To further explore the clinical efficacy, additional participants (up to 12 per cohort) may be enrolled at the optimal biologic dose (OBD) or maximum tolerated dose (MTD).

At the end of the study, participants may be enrolled into an open-label extension study (AO-101-EXT \[NCT02151903\]), at the discretion of the investigator.

A Study of De-immunized DI-Leu16-IL2 Administered Subcutaneously in Participants With B-cell NHL

A Phase I/II Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered Subcutaneously in Patients With B-cell Non-Hodgkin Lymphoma (NHL)

The MTD was determined based on toxicities from the first 2 cycles of treatment. The MTD was the highest dose tested with no more than 1 participant out of 6 experienced a dose-limiting toxicity (DLT). All non-hematologic adverse events (AEs) and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included absolute lymphocyte count (ALC) Grade 3 and 4 (if ALC does not resolve to baseline grade according to Common Terminology Criteria for Adverse Events (CTCAE) v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and absolute neutrophil count (ANC) Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).

All non-hematologic AEs and all hematologic AEs of greater than Grade 3 were considered relevant to determining DLTs. DLTs included ALC Grade 3 and 4 (if ALC does not resolve to baseline grade according to CTCAE v4 within 5 days post the final injection per cycle of DI-Leu16-IL2), and ANC Grade 3 (If ANC does not resolve to at least Grade 2 within 5 days post the final injection per cycle of DI-Leu16-IL2) and Grade 4 (any).

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 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.

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. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.

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. None of the participants were considered evaluable in 'DI-Leu16-IL2 0.5 mg/m\^2' arm for this outcome measure at the end of study, and therefore, data were not collected for that arm.

Participants received DI-Leu16-IL2 0.5 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

DI-Leu16-IL2 0.5 mg/m^2

Participants received DI-Leu16-IL2 1.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Participants received DI-Leu16-IL2 2.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Participants received DI-Leu16-IL2 4.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

DI-Leu16-IL2 4.0 mg/m^2

Participants received DI-Leu16-IL2 6.0 mg/m\^2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

DI-Leu16-IL2 6.0 mg/m^2

Age, Continuous

Tumor Measurement: Sum of Product of Diameters

Tumor Measurement: Sum of Longest of Diameters

Clinical benefit was noted in the earlier portion of the trial; hence, participants were not enrolled in 2 expansion cohorts and the study was terminated early.

Participants received assigned doses of DI-Leu16-IL2 SC for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Maximum Tolerated Dose (MTD) of DI-Leu16-IL2

Number of Participants With a DLT

Due to early termination of study, data for this outcome measure were not collected.

Number of Participants With Anti-DI-Leu16-IL2 Antibodies

Participants received DI-Leu16-IL2 0.5 milligrams per square meter (mg/m\^2) subcutaneously (SC) for 3 consecutive days every 3 weeks (21-day cycle) for a total of 4 cycles.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL	NCT02151903	B-cell Non-Hodg...	DI-Leu16-IL2	18 Years -	Alopexx Oncology, LLC
Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL	NCT02151903	B-cell Non-Hodg...	DI-Leu16-IL2	18 Years -	Alopexx Oncology, LLC
A Study of De-immunized DI-Leu16-IL2 Administered Subcutaneously in Participants With B-cell NHL	NCT01874288	B-cell Non-Hodg...	DI-Leu16-IL2	18 Years -	Alopexx Oncology, LLC

Spots Global Cancer Trial Database for il (interleukin)