CPG 7909 + Local Radiotherapy in Recurrent Low-Grade Lymphomas

NCT ID: NCT00185965

Last Updated: 2014-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-07-31
• Study Completion Date: 2010-03-31

Brief Summary

Brief summary TBD

Detailed Description

This is a single institution phase 1-2 trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas.

Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.

Conditions

Non-Hodgkin Lymphoma; Mycosis Fungoides

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lymphoma, B-cell low-grade (BCL)

Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure)

Group Type: EXPERIMENTAL

CPG 7909

Intervention Type: DRUG

6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections).

Mycosis fungoides (MF)

Mycosis fungoides patients must have failed or have been intolerant of at least 1 topical or 1 systemic treatment

Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment)

Group Type: EXPERIMENTAL

CPG 7909

Intervention Type: DRUG

6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections).

Interventions

CPG 7909

6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections).

Intervention Type: DRUG

Other Intervention Names

PF-3512676; CPG-enriched TLR9 agonist; CPG

Eligibility Criteria

Inclusion Criteria

• Biopsy confirmed low-grade B-cell lymphoma of any initial stage or mycosis fungoides of stage IB-IVA. B-cell lymphoma patients must have failed at least one prior treatment. Mycosis fungoides patients must have failed or have been intolerant of at least 2 topical or one systemic treatment.
• Patients must have at least one site of disease that is accessible for intratumoral injection of CpG percutaneously
• Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the treatment.
• Patients must have measurable disease other than the injection site or biopsy site.
• 18 years of age or older
• Karnofsky Performance Status (KPS) of > 70.
• Adequate bone marrow function: WBC>4,000uL, hemoglobin > 10g/dL; platelet count >100,000/mm3; ANC> 1000.
• Adequate hepatic function: bilirubin <= 1.5 mg/dL; SGOT/SGPT<3xupper limit of normal
• Adequate renal function: serum creatinine <= 2.0mg/dL.
• Required wash out periods for prior therapy:

• Topical therapy: 2 weeks
• Chemotherapy: 4 weeks
• Radiotherapy (including photo therapy): 4 weeks
• Systemic biological therapy for mycosis fungoides: 4 weeks
• Other investigational therapy: 4weeks
• 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.

Exclusion Criteria

• Pre-existing autoimmune or antibody mediated disease including: systemic lupus, erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the presence of autoantibodies without clinical autoimmune disease.
• Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active, prior treatment, or both).
• Patients with active infection or with a fever >38.50 C within three days prior to the first scheduled treatment.
• 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 attributed to compounds of similar composition to CpG 7909
• Current anticoagulant therapy (ASA<= 325mg/day allowed).
• Significant cardiovascular disease (i.e. 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 results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lymphoma Research Foundation

OTHER

Sponsor Role: collaborator

American Society of Clinical Oncology

OTHER

Sponsor Role: collaborator

Ronald Levy

OTHER

Sponsor Role: lead

Responsible Party

Ronald Levy

Robert K. and Helen K. Summy Professor in the School of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ronald Levy

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Countries

United States

References

Kim YH, Gratzinger D, Harrison C, Brody JD, Czerwinski DK, Ai WZ, Morales A, Abdulla F, Xing L, Navi D, Tibshirani RJ, Advani RH, Lingala B, Shah S, Hoppe RT, Levy R. In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study. Blood. 2012 Jan 12;119(2):355-63. doi: 10.1182/blood-2011-05-355222. Epub 2011 Nov 1.

Reference Type: RESULT

PMID: 22045986 (View on PubMed)

Brody JD, Ai WZ, Czerwinski DK, Torchia JA, Levy M, Advani RH, Kim YH, Hoppe RT, Knox SJ, Shin LK, Wapnir I, Tibshirani RJ, Levy R. In situ vaccination with a TLR9 agonist induces systemic lymphoma regression: a phase I/II study. J Clin Oncol. 2010 Oct 1;28(28):4324-32. doi: 10.1200/JCO.2010.28.9793. Epub 2010 Aug 9.

Reference Type: RESULT

PMID: 20697067 (View on PubMed)

Other Identifiers

80057

Identifier Type: OTHER

Identifier Source: secondary_id

LYMNHL0014

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-13063

Identifier Type: -

Identifier Source: org_study_id