Back to resultsOpen-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL
Primary Purpose
B-cell Non-Hodgkin Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
DI-Leu16-IL2
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Non-Hodgkin Lymphoma focused on measuring NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
Eligibility Criteria
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.
Sites / Locations
- City of Hope
- University of Minnesota
- Dartmouth-Hitchcock Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
DI-Leu16-IL2 1.0 mg/m^2
DI-Leu16-IL2 2.0 mg/m^2
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
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.
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
Secondary Outcome Measures
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02151903
Brief Title
Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL
Official Title
An Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Patients With B-cell Non-Hodgkin Lymphoma (NHL)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
Clinical benefit was noted before the scheduled completion of the trial and the extension study was terminated early.
Study Start Date
November 4, 2014 (Actual)
Primary Completion Date
July 11, 2016 (Actual)
Study Completion Date
July 11, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alopexx Oncology, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non-Hodgkin Lymphoma
Keywords
NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DI-Leu16-IL2 1.0 mg/m^2
Arm Type
Experimental
Arm Description
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.
Arm Title
DI-Leu16-IL2 2.0 mg/m^2
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
DI-Leu16-IL2
Intervention Description
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
Primary Outcome Measure Information:
Title
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria
Description
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.
Time Frame
First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months)
Title
Tumor Measurement: Percent Change From Baseline in Sum of Product of Diameters at the End of Study
Description
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.
Time Frame
Baseline, end of study (EOS) (up to approximately 32 months)
Title
Tumor Measurement: Percent Change From Baseline in Sum of Longest Diameters at the End of Study
Description
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
Time Frame
Baseline, EOS (up to approximately 32 months)
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
First dose of study drug up to EOS (up to 20 months)
Title
Number of Participants With a TEAE That Was Considered Related to a Clinically Significant Hematology or Serum Chemistry Abnormality
Description
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.
Time Frame
First dose of study drug up to EOS (up to 20 months)
Title
Number of Participants With a Clinically Significant Abnormal Physical Exam
Description
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.
Time Frame
First dose of study drug up to EOS (up to 20 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Vlock, MD
Organizational Affiliation
Alopexx Oncology, LLC
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
15076141
Citation
Ko YJ, Bubley GJ, Weber R, Redfern C, Gold DP, Finke L, Kovar A, Dahl T, Gillies SD. Safety, pharmacokinetics, and biological pharmacodynamics of the immunocytokine EMD 273066 (huKS-IL2): results of a phase I trial in patients with prostate cancer. J Immunother. 2004 May-Jun;27(3):232-9. doi: 10.1097/00002371-200405000-00008.
Results Reference
background
PubMed Identifier
15483010
Citation
King DM, Albertini MR, Schalch H, Hank JA, Gan J, Surfus J, Mahvi D, Schiller JH, Warner T, Kim K, Eickhoff J, Kendra K, Reisfeld R, Gillies SD, Sondel P. Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol. 2004 Nov 15;22(22):4463-73. doi: 10.1200/JCO.2004.11.035. Epub 2004 Oct 13.
Results Reference
background
PubMed Identifier
7522629
Citation
Maloney DG, Liles TM, Czerwinski DK, Waldichuk C, Rosenberg J, Grillo-Lopez A, Levy R. Phase I clinical trial using escalating single-dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC-C2B8) in patients with recurrent B-cell lymphoma. Blood. 1994 Oct 15;84(8):2457-66.
Results Reference
background
Links:
URL
http://www.alopexx.com
Description
Sponsor website
URL
http://www.cancer.gov/cancertopics/types/non-hodgkin
Description
National Cancer Institute at the National Institute of Health
Learn more about this trial
Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL
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