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

Primary Purpose

Lymphoma, Non-Hodgkin, Hodgkin Disease

Status

Terminated

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

SD-101

Local Radiation

About this trial

This is an interventional treatment trial for Lymphoma, Non-Hodgkin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

SD-101 + Combined with Local Radiation

Arm Description

Outcomes

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

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.

Measure tumor response by PET-CT scan imaging

Measure level of donor specific tumor infiltrating lymphocytes by flow cytometry and Immunofluorescence

Collect PBMCs

Full Information

NCT ID

NCT01745354

First Posted

December 6, 2012

Last Updated

November 17, 2016

Sponsor

Robert Lowsky

1. Study Identification

Unique Protocol Identification Number

NCT01745354

Brief Title

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

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Terminated

Why Stopped

Accrual issues - Slow accrual

Study Start Date

August 2012 (undefined)

Primary Completion Date

November 2014 (Actual)

Study Completion Date

November 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Robert Lowsky

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, Non-Hodgkin, Hodgkin Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

SD-101 + Combined with Local Radiation

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

SD-101

Other Intervention Name(s)

Dynavax

Intervention Description

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

Intervention Type

Radiation

Intervention Name(s)

Local Radiation

Primary Outcome Measure Information:

Title

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

Secondary Outcome Measure Information:

Title

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

Title

Measure tumor response by PET-CT scan imaging

Time Frame

8 weeks after treatment

Title

Measure level of donor specific tumor infiltrating lymphocytes by flow cytometry and Immunofluorescence

Description

Collect PBMCs

Time Frame

2, 3, 8 weeks after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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 One for diagnosis (lymph node or bone marrow biopsy) One palpable for treatment 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Lowsky

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Lauren Maeda

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University School of Medicine

City

Palo Alto

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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