Recombinant Flt3 Ligand, Poly-ICLC, and Radiation Therapy in Treating Patients with Untreated, Relapsed, or Refractory Low Grade B-Cell Lymphoma

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Status: Active

Description

This phase I / II trial studies how well recombinant Flt3 ligand, poly-ICLC, and radiation therapy work in treating patients low grade B-cell lymphoma that has not been treated, has come back (relapsed), or does not respond to treatment (refractory). Recombinant Flt3 ligand vaccine may help the body make more immune cells called dendritic cells. The poly-ICLC vaccine stimulates the immune system by activating the dendritic cells. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving recombinant Flt3 ligand, poly-ICLC, and radiation therapy may work better at treating low grade B-cell lymphoma.

Eligibility Criteria

Inclusion Criteria

  • Biopsy-confirmed low-grade B-cell lymphoma; specifically, follicular grade 1, 2, or 3A, marginal zone or small lymphocytic lymphoma, of any initial stage; patients in cohort A must be relapsed/refractory after at least one prior systemic therapy and patients in cohort B must have had no prior systemic therapy
  • Patients must have at least one site of disease that is accessible for intratumoral injection percutaneously (e.g. inguinal, axillary, cervical, or subcutaneous)
  • Tumor specimens must be available for immunological studies, either from a previous biopsy or a new biopsy obtained before the initiation day 1 of the study
  • Patients must have measurable disease other than the injection site or biopsy site, i.e. greater than 1.5 cm bi-dimensionally on standard computed tomography imaging
  • Eastern Cooperative Oncology Group (ECOG) performance status of 1 or better (corresponds to Karnofsky performance status [KPS] of >= 70)
  • White blood cells (WBC) >= 2,000/uL
  • Platelet count >= 75,000/mm^3
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Serum creatinine =< 2.0 mg/dL
  • Bilirubin =< 1.5 mg/dL
  • Serum glutamic-oxaloacetic transaminase (SGOT)/serum glutamate pyruvate transaminase (SGPT) < 3 x upper limit of normal
  • Required wash out periods for prior therapy (for cohort A): * Topical therapy: 2 weeks * Chemotherapy: 4 weeks * Radiotherapy: 4 weeks * Other investigational therapy: 4 weeks * Rituximab: 12 weeks
  • Patients of reproductive potential and their partners must agree to use an effective (> 90% reliability) form of contraception during the study and for 4 weeks following the last study drug administration
  • Women of reproductive potential must have negative urine pregnancy test
  • Life expectancy greater than 4 months
  • Able to comply with the treatment schedule
  • Ability to understand and the willingness to sign a written informed consent document
  • RETREATMENT
  • Patients who meet the retreatment criteria may receive retreatment at the investigator’s discretion; during retreatment, patients will follow the same schedule of assessments as the original treatment period
  • Criteria for retreatment through progression * A patient must meet all of the Inclusion criteria in order to be re-enrolled

Exclusion Criteria

  • Pre-existing autoimmune or antibody-mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia, history of uveitis; patients with controlled thyroid disease, or the presence of auto-antibodies without clinical autoimmune disease, are permitted on study
  • Known history of human immunodeficiency virus (HIV)
  • Patients with active infection or with a fever > 38.50 Celsius (C) within three days prior to the first scheduled  treatment
  • Known central nervous system (CNS) metastases
  • 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
  • History of allergic reactions to compounds of similar composition to either CDX-301 or poly-ICLC
  • Current anticoagulant therapy; (acetylsalicylic acid [ASA] =< 325 mg per day is allowed)
  • Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  • Pregnant or lactating
  • Any other medical history, including laboratory abnormalities, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results

Locations & Contacts

New York

New York
Icahn School of Medicine at Mount Sinai
Status: Active
Contact: Joshua Brody
Phone: 212-659-8297
Email: joshua.brody@mssm.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine local and systemic anti-tumor effects of intratumoral injection of recombinant Flt3 ligand (rhuFlt3L/CDX-301) and poly-ICLC combined with local radiation in patients with low-grade B-cell lymphoma.

SECONDARY OBJECTIVE:

I. To determine the feasibility and safety of this treatment regimen.

EXPLORATORY OBJECTIVE:

I. To evaluate humoral and cellular immune responses to the combined treatment regimen.

OUTLINE:

Patients receive recombinant Flt3 ligand intratumorally on days 1-5 and 8-11, and undergo radiation therapy on days 1 and 2. Beginning day 12, patients receive poly-ICLC intratumorally for up to 8 injections on weeks 2-8 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, every 3-6 months for 12 months, and then every 6-12 months thereafter.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
Joshua Brody

Trial IDs

Primary ID 13-1347
Secondary IDs NCI-2017-00655
Clinicaltrials.gov ID NCT01976585