Phase I Study of An Autologous Idiotype Vaccine Manufactured by magnICON® Technology for the Treatment of Patients with Follicular Lymphoma in First Relapse/Progression

Summary

This will be a prospective single -arm, open-label, phase I trial of patients with relapsed or transformed follicular lymphoma, who achieve a complete or partial remission after salvage chemotherapy who will receive an autologous idiotype vaccine manufactured by magnICON(TM) technology.

Salvage chemotherapy phase: Patients in relapse will receive salvage chemotherapy with a non-anti-CD20 containing regimen based on the drug bendamustine. Patients who enter a complete remission or a partial remission will enter the vaccination phase of the trial if in stable remission for 4 months after completion of bendamustine based chemotherapy.

Vaccination phase: Patients entering the vaccination phase of the study will receive subcutaneous injections of vaccine every 28 days (vaccinations 1 through 8). After vaccination 8, vaccinations will continue every 56 days until the 12th vaccination (i.e. a total duration of almost 16 months per patient).

Patients will be assessed for the primary endpoint analysis of safety and tolerability of the vaccine therapy after completion of the 6th vaccine injection (Secondary endpoints of immune responses to the vaccine will be assessed prior to the receipt of the 7th vaccine injection. Additional safety and tolerability will be assessed after completion of the 12th vaccine injection.

Approximate duration of subject participation: Patients will participate in this study for approximately 2 years: 4-6 months of salvage chemotherapy with a mandatory 4 month observation prior to vaccination with a maximum of nearly 16 months of vaccine therapy.

Approximate Number of Study Subjects: As the estimated overall response rate to salvage chemotherapy is 70%. Accounting for a 5% rate of technical complications in vaccine manufacture and a 5% study withdrawal rate, this trial will enroll 30-40 patients to identify the 20 patients who achieve a CR or PR by salvage chemotherapy and who will receive subsequent vaccination.

Participant Eligibility

1. a. Subjects with histologically proven follicular lymphoma relapsed after prior therapy OR b. transformed follicular lymphoma relapsed after prior anthracycline-containing therapy
2. 2. The tumor cells must express either an IgM or IgG on their surface. (
3. Age > 18 years.
4. ECOG performance status of 0-2.
5. Anticipated life expectancy of at least 12 months
6. Presence of at least a 2x2 cm in diameter either single lymph node or equivalent volume of lymph nodes accessible by physical examination for excision; for histological confirmation of diagnosis and for manufacture of the vaccine.
7. Measurable disease in neck, chest, abdomen, or pelvis as assessed by CT scan such that response to 2nd line chemotherapy can be defined. PET scan results are not required for enrollment.
8. Subjects may have had any number of prior treatment regimens. If enrolled with transformed follicular lymphoma, study subject must have had prior anthracycline in a previous regimen.
9. At least 4 months since last rituximab exposure.
10. Access to information regarding the duration of patient’s first remission.
11. Adequate bone marrow function at the start of the chemotherapy phase and at start of the vaccination phase by the following laboratory requirements designated as per study calendar prior to the start of each treatment:
• Hemoglobin ≥ 10.0 g/dl. (Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to study entry nor required during the study.)
• Absolute Neutrophil Count (ANC) ≥ 1500/mm3
• Platelet Count ≥ 100,000/μL
12. Adequate liver function at start of the chemotherapy phase and at start of vaccination phase designated as per study calendar and defined by the following:
• Total bilirubin ≤ 1.5 x ULN
• ALT and AST ≤ 2.5 x ULN
• Alkaline phosphatase < 4 x ULN
13. Adequate renal function at start of the salvage chemotherapy phase and at start of vaccination phase designated as per study calendar and defined by:
• Serum creatinine ≤ 1.5 x ULN
• OR calculated creatinine clearance > 60 ml/min
14. PT-INR/PTT < 1.5 x ULN prior to lymph node biopsy (Patients on therapeutic anticoagulation with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists).
15. Signed and dated informed consent