Intratumoral Poly-ICLC Plus Low Dose Local Radiation in Low Grade Recurrent B and T Cell Lymphoma

A Phase I Study of Intratumoral Poly-ICLC Plus Low Dose Local Radiation in Low Grade Recurrent B and T Cell Lymphoma

The primary objective of this study is to evaluate the safety of intratumoral Polyinosinicpolycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly-ICLC)(Hiltonol®) in addition to low-dose local radiotherapy for adult patients with low grade lymphomas, including follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, chronic lymphocytic leukemia, and cutaneous T-cell lymphoma. The secondary endpoints are response rate, immune responses, and durability of responses as well as generation of antiinflammatory response at sites of tumor involvement.

Study Overview

• Status: Terminated
• Conditions: B Cell Lymphoma; T Cell Lymphoma
• Intervention / Treatment: Drug: Poly-ICLC

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89135
      • Nevada Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must be at least 18 years of age.
2. Patients must have biopsy confirmed low-grade B-cell lymphoma (follicular, marginal zone, or small cell/chronic lymphocytic leukemia) or mycosis fungoides. B-cell lymphoma patients must have failed at least one prior therapy (chemotherapy or immunotherapy) or mycosis fungoides patients failed at least 1 topical or systemic treatment.
3. Patients must have at least one accessible tumor site that can be injected with poly-ICLC.
4. Patients must have measurable disease other than the injection site.
5. Patients must have a Karnofsky performance status of at least 70%.
6. Patients must have adequate hematologic, renal and liver function (i.e., absolute neutrophil count at least 1500/mm3, Platelets at least 100,000/mm3, creatinine no more than 1.7 mg/dl, total bilirubin no more than 1.5 mg/dl, transaminases no more than 4 times above the upper limits of the institutional normal).
7. Patients must be able to provide written informed consent.
8. Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. While animal testing has been negative, the anti-proliferative activity of this experimental drug may theoretically be harmful to the developing fetus or nursing infant.

9. Required washout period for prior therapy:

   • Topical therapy: 2 weeks.
   • Chemotherapy: 4 weeks
   • Radiotherapy: (including phototherapy): 4 weeks 13 of 26
   • Biological therapies: 4 weeks
   • Other investigational therapy: 4 weeks
   • Rituximab: 12 weeks

Exclusion Criteria:

1. Any history of autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, autoimmune hemolytic anemia, pure red cell aplasia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
2. Off nucleoside or bendustine therapy for a minimum of 6 months
3. Prior treatment with Campath
4. Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active, prior treatment, or both).
5. Patients with active infection or with a fever > 38.5°C within three days prior to the first scheduled treatment.
6. CNS metastases.
7. Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix.
8. Current anticoagulant therapy (ASA no more than 325 mg/day allowed).
9. Significant cardiovascular disease (i.e., NYHA class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias).
10. Pregnant or lactating.
11. Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Poly-ICLC; Poly-ICLC plus low dose local radiation.	Drug: Poly-ICLC; An accessible site of disease (lymph node, cutaneous, subcutaneous, etc.) will be selected by the principal investigator. Patients will then receive two doses of low dose irradiation (2 Gy per day) to that single site on days 1 and 2. Intratumorally or peritumorally Poly-ICLC will be dosed on days 3 and 4 by the physician during weeks 1, 2, 3, 4, and 8.; Other Names: Hiltonol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Toxicity (DLT)	Days 1 through 4 during weeks 1, 2, 3, 4, and 8

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor Response	Weeks 1 through 4, 8, 12, 16, and q3 months thereafter

Collaborators and Investigators

• Sponsor: Nevada Cancer Institute
• Collaborators: CLL Topics
• Investigators: Principal Investigator: Delva Deauna-Limayo, MD, Nevada Cancer Institute

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): May 1, 2010
• Study Completion (ACTUAL): April 1, 2011

Study Registration Dates

• First Submitted: April 10, 2009
• First Submitted That Met QC Criteria: April 13, 2009
• First Posted (ESTIMATE): April 14, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): July 20, 2011
• Last Update Submitted That Met QC Criteria: July 19, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Low Grade Recurrent B and T Cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Immunologic Factors; Interferon Inducers; Poly ICLC
• Other Study ID Numbers: NVCI-0838