B-cell Non-Hodgkin LymphomaPhase 1/2NCT02151903
Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Participants With B-cell NHL
A Phase 1/2 study testing DI-Leu16-IL2 in people with B-cell Non-Hodgkin Lymphoma, run by Alopexx Oncology, LLC at 3 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- B-cell Non-Hodgkin Lymphoma
- What is being tested?
- DI-Leu16-IL2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesUnited States
- Study dates
- 4 Nov 2014to 11 Jul 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
City of Hope
Duarte, California, 91010
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
University of Minnesota
Minneapolis, Minnesota, 55455
About this study
Official title: An Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Patients With B-cell Non-Hodgkin Lymphoma (NHL)
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.
- Conditions
- B-cell Non-Hodgkin Lymphoma
- Being tested
- DI-Leu16-IL2
- Keywords
- NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DI-Leu16-IL2Drug
DI-Leu16-IL2 will be administered per dose and schedule specified in the arm.
| Study group | Role | What they receive |
|---|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | Experimental | 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. Receives: Drug: DI-Leu16-IL2 |
| DI-Leu16-IL2 2.0 mg/m^2 | Experimental | 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. Receives: Drug: DI-Leu16-IL2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: Baseline, EOS (up to approximately 32 months)
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: First dose of study drug up to EOS (up to 20 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2014 (estimated)
- Study start4 Nov 2014
- Primary completion11 Jul 2016
- Study completion11 Jul 2016
Why it stopped: Clinical benefit was noted before the scheduled completion of the trial and the extension study was terminated early.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for B-cell Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alopexx Oncology, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel Vlock, MD, Study director, Alopexx Oncology, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02151903
- Sponsor's protocol ID
- AO-101-EXT
- Status last verified
- Nov 2020
- First submitted
- 23 May 2014
- Last updated
- 27 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 15076141King 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.
PubMed 15483010Maloney 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.
PubMed 7522629
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered in Patients With B-cell Non-Hodgkin Lymphoma (NHL)
- ClinicalTrials.gov ID
- NCT02151903
- Acronym / sponsor ID
- AO-101-EXT
- Conditions
- B-cell Non-Hodgkin Lymphoma
- Keywords
- NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Clinical benefit was noted before the scheduled completion of the trial and the extension study was terminated early.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Alopexx Oncology, LLCIndustry (pharma, biotech, devices)
- Study start
- 4 Nov 2014 (actual)
- Primary completion
- 11 Jul 2016 (actual)
- Study completion
- 11 Jul 2016 (actual)
- First posted
- 2 Jun 2014 (estimated)
- Results
- Posted 27 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DI-Leu16-IL2 1.0 mg/m^2 | Experimental | Drug: DI-Leu16-IL2Participants 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. |
| DI-Leu16-IL2 2.0 mg/m^2 | Experimental | Drug: DI-Leu16-IL2Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DI-Leu16-IL2DI-Leu16-IL2 will be administered per dose and schedule specified in the arm. | Drug | DI-Leu16-IL2 1.0 mg/m^2, DI-Leu16-IL2 2.0 mg/m^2 |
Primary outcome
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria
Time frame: First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months)
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
Time frame: Baseline, end of study (EOS) (up to approximately 32 months)
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
Time frame: Baseline, EOS (up to approximately 32 months)
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
3 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: 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
Time frame: First dose of study drug up to EOS (up to 20 months)
Number of Participants With a Clinically Significant Abnormal Physical Exam
Time frame: First dose of study drug up to EOS (up to 20 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15076141Ko 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.
- Background: PubMed 15483010King 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.
- Background: PubMed 7522629Maloney 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.
- Sponsor websiteLink provided by the sponsor.
- National Cancer Institute at the National Institute of HealthLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Daniel Vlock, MD study director
Alopexx Oncology, LLC
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DI-Leu16-IL2 in people with B-cell Non-Hodgkin Lymphoma, run by Alopexx Oncology, LLC at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Best Overall Response (BOR) Assessed Per International Workshop for Non-Hodgkin Lymphoma (NHL) Response Criteria (time frame: First dose of study drug until first appearance of CR, CRu, PR, SD, or PD (up to 20 months)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02151903, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Nov 2020.