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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2015 by Stanford University
Information provided by (Responsible Party):
Robert Lowsky, Stanford University Identifier:
First received: December 6, 2012
Last updated: September 8, 2015
Last verified: September 2015
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 anincreased 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.

Condition Intervention Phase
Lymphoma, Non-Hodgkin
Hodgkin Disease
Drug: SD-101
Radiation: Local Radiation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • 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 [ Time Frame: 60 Days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Measure cytotoxic T-cell activity changes pre- and post-treatment of tumor infiltrating lymphocytes and peripheral blood lymphocytes using ELISA and Immunohistochemistry. [ Time Frame: 2, 3, 8 weeks after treatment ] [ Designated as safety issue: No ]
  • Measure tumor response by PET-CT scan imaging [ Time Frame: 8 weeks after treatment ] [ Designated as safety issue: No ]
  • Measure level of donor specific tumor infiltrating lymphocytes by flow cytometry and Immunofluorescence [ Time Frame: 2, 3, 8 weeks after treatment ] [ Designated as safety issue: No ]
    Collect PBMCs

Estimated Enrollment: 12
Study Start Date: August 2012
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Dynavax
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).

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01745354

United States, California
Stanford University School of Medicine Recruiting
Palo Alto, California, United States, 94305
Contact: Physician Referrals    650-723-0822      
Sub-Investigator: Edgar G Engleman         
Sub-Investigator: Richard T Hoppe         
Sub-Investigator: Ronald Levy         
Sub-Investigator: Lauren Maeda         
Sub-Investigator: Samuel Strober         
Principal Investigator: Robert Lowsky         
Principal Investigator: Lauren Maeda         
Sponsors and Collaborators
Robert Lowsky
Principal Investigator: Robert Lowsky Stanford University
Principal Investigator: Lauren Maeda Stanford University
  More Information

No publications provided

Responsible Party: Robert Lowsky, Associate Professor of Medicine, Stanford University Identifier: NCT01745354     History of Changes
Other Study ID Numbers: BMT235, SU-07212011-8129, 20741
Study First Received: December 6, 2012
Last Updated: September 8, 2015
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Hodgkin Disease
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type processed this record on December 01, 2015