Trial Information

Phase II Randomized Trial of Early Versus Late Vaccination in Patients With High Risk CLL

OBJECTIVES:

- Determine the efficacy and toxicity of cyclophosphamide and rituximab in patients with
previously untreated, high-risk chronic lymphocytic leukemia.

- Determine, preliminarily, the efficacy and toxicity of early vs delayed administration
of vaccine therapy comprising KGEL and autologous tumor cells after cyclophosphamide
and rituximab in these patients.

- Compare the magnitude of the T-cell response to early vs delayed administration of this
vaccine after rituximab and cyclophosphamide and correlate these responses with the
extent of immune reconstruction.

OUTLINE: This is a randomized phase II study for patients with asymptomatic or minimally
symptomatic, untreated CLL with poor-risk features.

Patients undergo peripheral blood collection for vaccine production. Patients then receive
rituximab IV over at least 4 hours on days 1 and 2 in course 1 and on day 1 only in
subsequent courses and cyclophosphamide IV over 1 hour on day 1. Treatment with rituximab
and cyclophosphamide repeats every 21 days for up to 6 cycles in the absence of disease
progression. Patients undergo evaluation 4 weeks after completion of rituximab and
cyclophosphamide. Patients achieving partial or complete response are randomized to 1 of 2
vaccine treatment arms.

- Arm I (early administration): Beginning 2 weeks after evaluation, patients receive
vaccine therapy comprising an autologous tumor admixed with an allogeneic vaccine
(KGEL) that produces sargramostim (GM-CSF) and autologous tumor cells intradermally.
Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.

- Arm II (late administration): Beginning 20 weeks after evaluation, patients receive
vaccine therapy comprising KGEL and autologous tumor cells intradermally. Treatment
repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 1 year and
then every 6 months until disease progression.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.