A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of Patient-Specific Immunotherapy, Recombinant Idiotype Conjugated to KLH (Id-KLH) and Administered With GM-CSF, in Patients With CNS Lymphoma

Trial Information

A Phase 2, Open-Label Study to Evaluate the Efficacy and Safety of Patient-Specific Immunotherapy, Recombinant Idiotype Conjugated to KLH (Id-KLH) and Administered With GM-CSF, in Patients With CNS Lymphoma

OBJECTIVES:

Primary

- To determine the proportion of patients with CNS lymphoma who develop anti-idiotype
(Id) and anti-keyhole limpet hemocyanin (KLH) humoral immune responses in the serum
and/or CSF following patient-specific immunotherapy comprising recombinant
tumor-derived immunoglobulin Id-KLH conjugate vaccine and sargramostim (GM-CSF).

- To assess the safety and tolerability of this regimen in these patients.

Secondary

- To evaluate the progression-free survival (PFS) of patients treated with this regimen.

- To determine the time to receipt of first subsequent anti-lymphoma therapy after
initiating immunization with the Id-KLH conjugate vaccine.

- To assess the correlation of anti-Id immune response in the CSF and/or serum with PFS
and overall survival.

Tertiary

- To evaluate the kinetics of humoral immune response development in patients treated
with this regimen.

OUTLINE:

- Pre-immunotherapy: Patients submit a tumor sample for manufacturing of the idiotype
(Id)-keyhole limpet hemocyanin (KLH) conjugate vaccine and undergo placement of an
Ommaya reservoir. Patients then receive induction therapy comprising methotrexate IV
once every 2 weeks until a maximum radiographic response is achieved, as assessed by
MRI of the brain. Patients then receive methotrexate IV once a month for 6 months.
Patients with leptomeningeal or CSF involvement also receive intraventricular thiotepa
twice a week until the CSF is clear on three evaluations and then once a week until the
CSF is clear on four evaluations. Patients under 55 years of age also undergo whole
brain radiotherapy (or craniospinal radiotherapy when extensive leptomeningeal disease
is present). Patients who achieve a stable response to induction therapy proceed to
immunotherapy.

- Immunotherapy: Patients receive recombinant tumor-derived immunoglobulin Id-KLH
conjugate vaccine subcutaneously (SC) on day 1 of weeks 0, 2, 4, 6, 8, 10, 12, 16, 20,
24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, and 76. Patients also receive
sargramostim (GM-CSF) SC on days 1-4 of the same weeks as the Id-KLH conjugate vaccine.

After completion of therapy, patients are followed periodically for up to 2 years.