Phase I/II Study of De-immunized DI-Leu16-IL2 Immunocytokine Administered Subcutaneously in Patients With B-cell NHL
B-cell Non-Hodgkin Lymphoma
Conditions: official terms
Lymphoma, B-Cell - Lymphoma, Non-Hodgkin
Conditions: Keywords
NHL, Immunocytokine, Lymphoma, Non-Hodgkin, B-cell, IL (interleukin)
Study Type
Study Phase
Phase 1/Phase 2
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: 0.5 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 1.0 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 2.0 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 4.0 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 6.0 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 8.0 mg/m2 DI-Leu16-IL2 Type: Drug
Name: 10.0 mg/m2 DI-Leu16-IL2 Type: Drug
Overall Status
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.

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.
Detailed Description
1. 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.

2. 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.

3. To measure the response rate at the MTD (and/or OBD) associated with the proposed therapy and survival endpoints of the enrolled patients.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
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. Measurable disease. In the absence of lymphadenopathy, splenomegaly with defects or measurable extra-medullary disease is acceptable. Patients with bone marrow involvement alone will not be included

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. Lymphocyte count ≥0.5 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 (UNL)

7. Aspartate aminotransferase (AST) <2.5 x UNL

8. Total bilirubin (TBili) <1.5 x ULN

9. Sodium, potassium, and phosphorus within normal limits

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 ≤ 450 ms

12. Cardiac stress test (e.g., stress thallium scan, stress echocardio¬graphy) with normal results if patient is suspected to have coronary artery disease.

10. Patients must use adequate birth control measures 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

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

19. Circulating levels of rituximab > 75.0 µg/ml
City of Hope
Duarte, California, United States
Status: Recruiting
Contact: - 626-256-4673 -
University of Minnesota
Minneapolis, Minnesota, United States
Status: Recruiting
Contact: Veronika Bachanova, M.D. - 612-625-5469 -
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Status: Recruiting
Contact: - 603-650-5529 -
Joe Arlington Cancer Research and Treatment Center
Lubbock, Texas, United States
Status: Recruiting
Contact: Donald P Quick, MD - 806-725-8000
Start Date
July 2013
Completion Date
July 2015
Alopexx Oncology, LLC
Alopexx Oncology, LLC
Record processing date processed this data on July 28, 2015 page