Clinical trial NCT01745354: Immunostimulatory CpG SD-101 + RT in Recurrent/Progressive Lymphoma After Allogeneic Hematopoietic Cell Transplantation (HCT)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Hodgkin Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2012-12-10
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 60 Days
Secondary outcomes:
measure: Measure cytotoxic T-cell activity changes pre- and post-treatment of tumor infiltrating lymphocytes and peripheral blood lymphocytes using ELISA and Immunohistochemistry.
timeFrame: 2, 3, 8 weeks after treatment
measure: Measure tumor response by PET-CT scan imaging
timeFrame: 8 weeks after treatment
measure: Measure level of donor specific tumor infiltrating lymphocytes by flow cytometry and Immunofluorescence
timeFrame: 2, 3, 8 weeks after treatment
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Robert Lowsky
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Lauren Maeda
role: PRINCIPAL_INVESTIGATOR
References: