Phase II Pilot Trial to Evaluate the Efficacy of a Combined Therapy Approach for Young CLL Patients With Advanced and Progressive Disease Stratified According to the Biological Prognostic Features
- Determine the antitumor activity of induction therapy comprising fludarabine phosphate
with either alemtuzumab or cyclophosphamide followed by peripheral blood stem cell
transplantation or alemtuzumab in patients with advanced or progressive chronic
- Determine the toxicity of this regimen in these patients.
- Determine the length of survival, event-free survival, and disease-free survival of
patients treated with this regimen.
- Evaluate the relationship between different clinical and biological disease
characteristics, therapeutic response, and survival.
OUTLINE: This is a pilot, multicenter study. Patients are stratified according to biological
risk profile (high vs low risk).
- Group 1 (high-risk patients):
- Induction therapy: Patients receive fludarabine phosphate IV and alemtuzumab IV on
days 1-3. Treatment repeats for 4 courses.
Patients with no response (no good clinical partial response, steady disease, or progressive
disease) after induction therapy are removed from the study. Other patients proceed to
post-induction therapy based on response to induction therapy.
- Post-induction therapy:
- Complete clinical, cytometric, and molecular response: Patients undergo peripheral
blood stem cell (PBSC) mobilization with cytarabine IV twice daily on days 1-3 and
filgrastim (G-CSF) followed by no further therapy.
- Response to induction therapy and evidence of residual disease (complete clinical
and cytometric response with molecular evidence of disease; complete clinical
response only; or good clinical partial response): Patients without an HLA
familial matched donor undergo PBSC mobilization with cytarabine IV twice daily on
days 1-3 and G-CSF. Patients with sufficient harvested autologous PBSCs undergo
autologous PBSC transplantation (with BEAM conditioning regimen [carmustine,
etoposide, cytarabine, and melphalan]). Patients without sufficient harvested
- PBSCs receive alemtuzumab subcutaneously (SC) weekly for 6 weeks. Patients who do
not achieve molecular remission after 6 weeks of alemtuzumab receive 6 additional
weeks of treatment. Patients with an HLA familial matched
- undergo reduced-intensity allogeneic stem cell transplantation (with
cyclophosphamide, thiotepa, and fludarabine phosphate as conditioning regimen).
- Group 2 (low-risk patients):
- Induction therapy: Patients receive fludarabine phosphate and cyclophosphamide on days
1-3. Treatment repeats every month for 4 courses. Patients achieving at least a partial
response receive 2 additional courses.
Patients achieving complete clinical response with cytometric and molecular response;
complete clinical response with a cytometric response; or complete clinical response after
completion of induction therapy (i.e., partial response or greater) receive no further
treatment. Patients with no response or disease progression proceed to post-induction
- Post-induction therapy: Patients receive alemtuzumab SC weekly for 6 weeks. Patients
who do not achieve complete remission after 6 weeks of alemtuzumab receive 6 additional
weeks of treatment.
PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Complete response and partial response
At 2 years from study entry
Roberto Foa, MD
Universita Degli Studi "La Sapeinza"
Italy: Ethics Committee