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

NCT02151903 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: AO-101-EXT
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

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.

Conditions

B-cell Non-Hodgkin Lymphoma

Keywords

NHL; Immunocytokine; Lymphoma; Non-Hodgkin; B-cell; IL (interleukin)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (3)

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

  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

  First dose of study drug up to EOS (up to 20 months)

• Number of Participants With a Clinically Significant Abnormal Physical Exam

  First dose of study drug up to EOS (up to 20 months)

Study Arms (2)

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.

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.

Drug: DI-Leu16-IL2

Interventions

DI-Leu16-IL2 DRUG

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

DI-Leu16-IL2 1.0 mg/m^2; DI-Leu16-IL2 2.0 mg/m^2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alopexx Oncology, LLC: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Related Publications (3)

• 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.

  PMID: 15076141 BACKGROUND

• 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.

  PMID: 15483010 BACKGROUND

• 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.

  PMID: 7522629 BACKGROUND

Related Links

• Sponsor website
• National Cancer Institute at the National Institute of Health

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

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

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Alopexx Oncology, LLC

daniel.vlock@alopexx.com

Study Officials

• Daniel Vlock, MD

  Alopexx Oncology, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2014
• First Posted: June 2, 2014
• Study Start: November 4, 2014
• Primary Completion: July 11, 2016
• Study Completion: July 11, 2016
• Last Updated: November 27, 2020
• Results First Posted: November 27, 2020

Record last verified: 2020-11

Locations

US (3)