Immunostimulatory CpG SD-101 + RT in Recurrent/Progressive Lymphoma After Allogeneic Hematopoietic Cell Transplantation (HCT)

Intratumoral Injection of an Immunostimulatory CpG, SD-101, Combined With Local Radiation for the Treatment of Recurrent or Progressive Lymphoma After Allogeneic Hematopoietic Cell Transplantation

For patients with lymphoma that recurs after chemotherapy, bone marrow transplantation using cells from a healthy donor represents potentially curative treatment. In these individuals, cure is possible because transplantation of healthy donor immune cells can fight the lymphoma in the patient. The goal of this work is to test a strategy that activates the healthy donor immune cells so that they more effectively fight lymphoma and can result in an increased cure rate for these patients. Our group has previously studied CpG, an immune activating medication, in patients with lymphoma and demonstrated modest anti-tumor responses. We now have a more potent form of CpG which we intend to test to see if it will better activate the donor immune cells and result in shrinkage of tumor throughout the entire body, not just at the injected site.

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Non-Hodgkin; Hodgkin Disease
• Intervention / Treatment: Drug: SD-101; Radiation: Local Radiation

Detailed Description

Patients will receive low dose radiation to all bulky or symptomatic lymph nodes on days -2 and -1. SD-101 will be administered intratumorally to the single largest palpable node within 24 hours after completion of radiation, on day 0. Two additional intratumoral SD-101 injections will be performed on days 7 (+/- 2 days) and 14 (+/- 2 days). This is a dose ranging study using a 3+3 design with a definition of maximum tolerated dose (MTD) which our group has found acceptable in the past. The first cohort of patients will receive a SD-101 dose of 0.3 mg per injection. The dose will be escalated to 1 mg and 3 mg based on dose limiting toxicity (DLT).

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Stanford University School of Medicine

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:

• Biopsy-confirmed relapsed, refractory, or progressive NHL or HL (Refer to Section 3.2.1 for excluded subtypes)

• At least 3 sites of disease

  1. One for diagnosis (lymph node or bone marrow biopsy)
  2. One palpable for treatment
  3. One measurable radiographically
• > 60 days after RIC allogeneic transplant for lymphoma
• 18 years of age or older
• Mixed (5-95%) or complete (>95%) chimerism
• Eastern Oncology Cooperative Group (ECOG) performance status ≤ 2
• ANC >1000/mm3, platelets >50,000/mm3
• Total bilirubin ≤ 2.5 mg/dL, AST and ALT < 3 times upper limit of normal
• Serum creatinine ≤ 3 mg/dL
• No chemotherapy, RT, DLI or biologic therapy for lymphoma at least 4 weeks prior to scheduled treatment
• Minimal immunosuppression (defined as monotherapy with ≤ 10 mg prednisone daily, ≤ 200 mg cyclosporine daily, or ≤ 2 mg tacrolimus daily) at least 2 weeks prior to scheduled treatment

Exclusion Criteria:

• HIV associated lymphoma
• Acute GVHD at time of enrollment (history of treated and resolved GVHD is permitted)
• Active infection within 14 days prior to scheduled treatment
• Active Cytomegalovirus (CMV) disease at the time of enrollment
• Pre-existing autoimmune or antibody mediated disease (including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, and autoimmune thrombocytopenia)
• Pregnant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SD-101 + Combined with Local Radiation	Drug: SD-101; SD-101 will be administered after radiation to only the largest palpable lymph node as an intratumoral injection weekly for 3 weeks at three dosing cohorts: 0.3 mg, 1 mg, and 3 mg; Other Names: Dynavax; Radiation: Local Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determination of the maximum tolerated dose based on dose limiting toxicity defined as any new grade 3-4 toxicity after the first SD-101 administration	60 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure cytotoxic T-cell activity changes pre- and post-treatment of tumor infiltrating lymphocytes and peripheral blood lymphocytes using ELISA and Immunohistochemistry.		2, 3, 8 weeks after treatment
Measure tumor response by PET-CT scan imaging		8 weeks after treatment
Measure level of donor specific tumor infiltrating lymphocytes by flow cytometry and Immunofluorescence	Collect PBMCs	2, 3, 8 weeks after treatment

Collaborators and Investigators

• Sponsor: Robert Lowsky
• Investigators: Principal Investigator: Lauren Maeda, Stanford University

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (ACTUAL): November 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 6, 2012
• First Posted (ESTIMATE): December 10, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): November 18, 2016
• Last Update Submitted That Met QC Criteria: November 17, 2016
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: BMT235; SU-07212011-8129 (OTHER: Stanford University); 20741 (OTHER: stanford IRB)