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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
B-cell Non-Hodgkin Lymphoma

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Trial Information

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


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.


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. Age ≥18 years

5. Karnofsky performance scale ≥70%

6. Life expectancy ≥12 weeks

7. Adequate baseline functions:

1. Serum creatinine ≤1.5 mg/dl

2. Total white blood cell count ≥3000/uL or absolute neutrophil count ≥1000/uL

3. Lymphocyte count ≥0.5 x 10^3/uL

4. Platelet count ≥75,000/uL

5. Hematocrit ≥ 25% or hemoglobin ≥9 g/100 ml

6. Alanine aminotransferase <2.5 x upper limit of normal (ULN)

7. Aspartate aminotransferase <2.5 x ULN

8. Total bilirubin <1.5 x ULN

9. Sodium, potassium, and phosphorus within normal limits

10. Chest x-ray 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 and Diffusing Capacity of the Lung for Carbon Monoxide
of at least 65% and 50% of expected, respectively

11. Electrocardiogram corrected QT interval ≤ 450 ms

12. Cardiac stress test with normal results if patient is suspected to have coronary
artery disease

13. Fasting blood glucose <160 mg/dl and hemoglobin A1C <7% for patients with
Diabetes Mellitus (DM) or borderline DM

8. 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

9. 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

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
sero-positive 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 LNs (> 10 cm) or marked splenomegaly

19. Circulating levels of rituximab > 25.0 µg/ml

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of DI-Leu16-IL2

Outcome Description:

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.

Outcome Time Frame:

6 month treatment period

Safety Issue:

Yes

Principal Investigator

Daniel Vlock, MD

Investigator Role:

Study Director

Investigator Affiliation:

Alopexx Oncology, LLC

Authority:

United States: Food and Drug Administration

Study ID:

AO-101

NCT ID:

NCT01874288

Start Date:

June 2013

Completion Date:

July 2015

Related Keywords:

  • B-cell Non-Hodgkin Lymphoma
  • NHL
  • Immunocytokine
  • Lymphoma
  • Non-Hodgkin
  • B-cell
  • IL (interleukin)
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell

Name

Location

Dartmouth-Hitchcock Medical CenterLebanon, New Hampshire  03756
City of HopeDuarte, California  91010