Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01874288
Recruitment Status : Completed
First Posted : June 11, 2013
Last Update Posted : January 17, 2018
Sponsor:
Information provided by (Responsible Party):
Alopexx Oncology, LLC

Brief Summary:
An open-label, dose-escalation trial of the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to patients with CD20 (B-lymphocyte antigen CD20) positive Non-Hodgkin Lymphoma (NHL) that have failed standard rituximab-containing therapy. Following peripheral blood B cell depletion with rituximab (if needed) each patient will receive DI-Leu16-IL2 administered as a subcutaneous (SC) injection for three consecutive days every three weeks.

Condition or disease Intervention/treatment Phase
B-cell Non-Hodgkin Lymphoma Drug: 0.5 mg/m2 DI-Leu16-IL2 Drug: 1.0 mg/m2 DI-Leu16-IL2 Drug: 2.0 mg/m2 DI-Leu16-IL2 Drug: 4.0 mg/m2 DI-Leu16-IL2 Drug: 6.0 mg/m2 DI-Leu16-IL2 Drug: 8.0 mg/m2 DI-Leu16-IL2 Drug: 10.0 mg/m2 DI-Leu16-IL2 Drug: 50mg/m2 Rituximab Phase 1 Phase 2

Detailed Description:

An open-label, dose-escalation trial of the safety, tolerability, pharmacokinetics (PK), biological, and clinical activity of DI-Leu16-IL2 administered to patients with CD20 (B-lymphocyte antigen CD20) positive Non-Hodgkin Lymphoma (NHL) that have failed standard rituximab-containing therapy. Following peripheral blood B cell depletion with rituximab (if needed) each patient will receive DI-Leu16-IL2 administered as a subcutaneous (SC) injection for three consecutive days every three weeks (21 day cycle). Three to six (3-6) patients will be enrolled in each cohort. Patients may receive 6 cycles of DI-Leu16-IL2 approximately thrice weekly for 3 weeks for a total of 18 doses.

Approximately 66 patients will be enrolled in this study at approximately 6 investigational centers in the U.S. Forty-two (42) patients will be enrolled during dose escalation (Phase 1) and 2 expansion cohorts of 12 patients each (Phase 2).

Following completion of the Phase I portion of the trial and review of the safety, response and correlative immune data it has been elected to have 2 expansion cohorts of 12 patients each at 2 mg/m2.

  • Diffuse Large B-Cell Lymphoma (DLBCL) that is relapsed or refractory to standard therapy
  • All other CD20-expressing B-cell NHL that is relapsed or refractory to standard therapy. As mentioned above Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) with peripheral blood leukemia/lymphoma cells and high-grade lymphomas (i.e. Lymphoblastic Lymphoma/Burkitt's Lymphoma) are excluded

At the end of the study, patients may be enrolled into an open-label extension study (Study AO-101-EXT), at the discretion of the investigator.

Study Primary Endpoints

  1. To determine the maximum tolerated dose (MTD) of DI-Leu16-IL2 administered SC following peripheral blood B cell depletion with rituximab in patients with B-cell NHL.
  2. To investigate the optimal biologic dose (OBD) of DI-Leu16-IL2 following peripheral blood B cell depletion with rituximab in patients with B-cell NHL, which may differ from the MTD.
  3. To describe the toxicities associated with the proposed DI-Leu16-IL2 regimen.

Study Secondary Endpoints

  1. To evaluate the immunogenicity as measured by the induction of DI-Leu16-IL2-specific antibodies.
  2. To evaluate the PK of DI-Leu16-IL2 (achieved in the primary portion of the study).
  3. To measure the response rate at the MTD (and/or OBD) associated with the proposed therapy and survival endpoints of the enrolled patients.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered Subcutaneously in Patients With B-cell Non-Hodgkin Lymphoma (NHL)
Study Start Date : July 2013
Actual Primary Completion Date : September 2016
Actual Study Completion Date : September 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arm Intervention/treatment
Experimental: 0.5 mg/m2 DI-Leu16-IL2
0.5 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout the Phase 1 of the study.
Drug: 0.5 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 1.0 mg/m2 DI-Leu16-IL2
1.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout Phase 1 of the study.
Drug: 1.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 2.0 mg/m2 DI-Leu16-IL2
2.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout the study.
Drug: 2.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 4.0 mg/m2 DI-Leu16-IL2
4.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout Phase 1 of the study.
Drug: 4.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 6.0 mg/m2 DI-Leu16-IL2
6.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout Phase 1 of the study.
Drug: 6.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 8.0 mg/m2 DI-Leu16-IL2
8.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout Phase 1 of the study.
Drug: 8.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

Experimental: 10.0 mg/m2 DI-Leu16-IL2
10.0 mg/m2 DI-Leu16-IL2 subcutaneous dose administered to patients thrice weekly every three weeks for a total of 18 doses. Patients may receive approximately 6 cycles of DI-Leu16-IL2 and will remain on the same dose throughout Phase 1 of the study.
Drug: 10.0 mg/m2 DI-Leu16-IL2
If dose limiting toxicities are observed in one of the initial three patients enrolled in a dose level, then, another three patients must be enrolled at the same level before dose escalation can proceed. Each patient will receive the same dose level assigned at the time of enrollment. No intra- patient dose escalation will be permitted.

50mg/m2 Rituximab
Pre-treatment with Rituximab will occur on Day 1 if patient's Rituximab level is <10 μg/mL; intended to bring their level above10 μg/mL.
Drug: 50mg/m2 Rituximab
Pre-treatment with Rituximab will occur on Day 1 if patient's Rituximab level is <10 μg/mL; intended to bring their level above10 μg/mL.
Other Name: Rituximab




Primary Outcome Measures :
  1. Maximum tolerated dose of DI-Leu16-IL2 [ Time Frame: 6 month treatment period ]
    To determine the maximum tolerated dose of DI-Leu16-IL2 administered following peripheral blood B cell depletion with rituximab in patients with B-cell NHL.


Secondary Outcome Measures :
  1. Evaluate immunogenicity [ Time Frame: pre-dose on Day 1 of Cycles 1-4 ]
    To evaluate the immunogenicity as measured by the induction of DI-Leu16-IL2-specific antibodies.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with CD20-expressing B-cell NHL that is relapsed or refractory to standard therapy. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma with peripheral blood leukemia/lymphoma cells and high-grade lymphomas are excluded
  2. Patients must have received prior rituximab-containing therapy.
  3. Evaluable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable
  4. Patients who have received a prior autologous stem cell transplant are eligible if the transplant occurred > 6 months ago.
  5. Patients who have received a prior allogeneic stem cell transplant are eligible if:

    1. The transplant occurred > 6 months ago
    2. There is no evidence of active graft vs host disease
    3. Systemic immunosuppressive agents (including corticosteroids) have not been received for at least 8 weeks
  6. Age ≥18 years
  7. Karnofsky performance scale ≥70%
  8. Life expectancy ≥12 weeks
  9. Adequate baseline functions:

    1. Serum creatinine ≤ 1.5 mg/dl
    2. Total white blood cell count (WBC) ≥ 3000/µl, or absolute neutrophil count (ANC) ≥ 1000/µl
    3. Absolute lymphocyte count ≥0.75 x 10^3/µl
    4. Platelet count ≥75,000/µl
    5. Hematocrit ≥ 25% or hemoglobin ≥9 g/100 mL
    6. Alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN)
    7. Aspartate aminotransferase (AST) <2.5 x UNL
    8. Total bilirubin (TBili) <1.5 x ULN
    9. Sodium, potassium, and phosphorus levels no worse than grade 1
    10. Chest x-ray (CXR) or computed tomography CT within 4 weeks prior to Day 1 with no evidence of pulmonary congestion, pleural effusions, pulmonary fibrosis, or significant emphysema. If results are questionable, patients should have additional lung function testing to exclude clinically relevant restriction or obstruction. Patients must have a forced expiratory volume (FEV-1) and Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) of at least 65% and 50% of expected, respectively.
    11. Electrocardiogram (12-lead ECG) QTc ≤ 480 ms
    12. Cardiac stress test (e.g., stress thallium scan, stress echocardiography) with normal results if patient is suspected to have coronary artery disease.
  10. Patients participating in the study are to use adequate birth control measures (abstinence, oral contraceptives, barrier method with spermicide or surgical sterilization) during study participation. Females of childbearing potential must have a negative serum pregnancy test on the days of dosing. A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months.
  11. Provide written informed consent prior to any screening procedures

Exclusion Criteria:

  1. Evidence of central nervous system lymphoma or lymphomatous meningitis
  2. Prior treatment with IL2 within the last 5 years
  3. Type I hypersensitivity or anaphylactic reactions to murine proteins or to previous infusion of rituximab
  4. Pregnant or lactating female
  5. An immediate need for palliative radiotherapy or systemic corticosteroid therapy
  6. Known intercurrent infections (including hepatitis C virus and human immunodeficiency virus or other conditions), or clinical evidence of these conditions
  7. Actively infected with or chronic carriers of hepatitis B virus as demonstrated by positive hepatitis B core antibody or hepatitis B surface antigen. (Patients who are seropositive only, i.e. surface antibody positive [HbsAb], are permitted)
  8. Other significant active infection.
  9. Major surgery, chemotherapy, investigational agent, or radiation within 30 days of Day 1
  10. Uncontrolled hypertension (diastolic greater to or equal to 100 mmHg) or hypotension (systolic less than or equal to 90 mmHg)
  11. History of repeated and clinically relevant episodes of syncope or other paroxysmal, ventricular, or other significant arrhythmias
  12. History of medically significant ascites requiring repetitive paracentesis
  13. Previous diagnosis of autoimmune disease (Exceptions: patients with autoimmune thyroiditis or vitiligo may be enrolled)
  14. Organ transplant recipient
  15. History of prior therapy or a serious, uncontrolled medical disorder that in the Investigator's opinion would impair participation in the study
  16. Known hypersensitivity to Tween-80, or human immunoglobulin
  17. Legal incapacity or limited legal capacity
  18. Patients with bulky lymph nodes (LNs) (≥10 cm) or marked splenomegaly (i.e. extending into pelvis or crossing the midline).
  19. Circulating levels of rituximab > 75.0 µg/ml

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01874288


Locations
Layout table for location information
United States, California
City of Hope
Duarte, California, United States, 91010
St. Jude Hospital Yorba Linda
Fullerton, California, United States, 92835
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, Texas
Joe Arlington Cancer Research and Treatment Center
Lubbock, Texas, United States, 97410
Sponsors and Collaborators
Alopexx Oncology, LLC
Investigators
Layout table for investigator information
Study Director: Daniel Vlock, MD Alopexx Oncology, LLC

Additional Information:
Publications:
Layout table for additonal information
Responsible Party: Alopexx Oncology, LLC
ClinicalTrials.gov Identifier: NCT01874288     History of Changes
Other Study ID Numbers: AO-101
First Posted: June 11, 2013    Key Record Dates
Last Update Posted: January 17, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Alopexx Oncology, LLC:
NHL
Immunocytokine
Lymphoma
Non-Hodgkin
B-cell
IL (interleukin)
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Interleukin-2
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents