Clinical trial NCT00462332: Fludarabine and Alemtuzumab or Cyclophosphamide Followed by Peripheral Blood Stem Cell Transplant or Alemtuzumab in Treating Patients With Advanced or Progressive Chronic Lymphocytic Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
Lead sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
Sponsor class: OTHER
First posted: 2007-04-19
Enrollment: 86
Sex: ALL
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. A peripheral stem cell transplant using stem cells from the patient or a donor may replace the patient's immune cells that were destroyed by chemotherapy.

PURPOSE: This phase II trial is studying how well giving fludarabine together with alemtuzumab or cyclophosphamide followed by peripheral blood stem cell transplant or alemtuzumab works in treating patients with advanced or progressive chronic lymphocytic leukemia.

Detailed description: OBJECTIVES:

Primary

* 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 lymphocytic leukemia.

Secondary

* 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 therapy.

* 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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of chronic lymphocytic leukemia (CLL)

  * Advanced or progressive disease with ≥ 2 active clinical signs

PATIENT CHARACTERISTICS:

* Fertile patients must use adequate contraception
* No positive Coomb's test with signs of hemolysis
* No active infection
* No uncontrolled severe disease
* No known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
* No other malignancies within the past 2 years except for adequately treated malignancies
* No significant traumatic injury within the past 4 weeks
* No coexisting medical or psychological condition that would limit study compliance

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior treatment for CLL
* No major surgery within the past 4 weeks
* No prior chemotherapy

Primary outcomes:
measure: Number of Patients With Complete Response
timeFrame: At 2 years from study entry
Secondary outcomes:
measure: Toxicity
timeFrame: At 2 years from study entry
measure: Length of Survival
timeFrame: At 2 years and a half from study entry
measure: Event-free Survival
timeFrame: At 2 years from study entry
measure: Disease-free Survival
timeFrame: At 2 years from study entry
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo
city: Bari
country: Italy
facility: Universita Degli Studi di Bari
city: Campobasso
country: Italy
facility: Universita Cattolica del Sacro Cuore - Campobasso
city: Catania
country: Italy
facility: Università di Catania - Cattedra di Ematologia - Ospedale "Ferrarotto"
city: Catanzaro
country: Italy
facility: Ospedale Regionale A. Pugliese
city: Cosenza
country: Italy
facility: Ospedale Civile Cosenza
city: Ferrara
country: Italy
facility: Universita di Ferrara
city: Firenze
country: Italy
facility: Azienda Ospedaliera di Firenze
city: Genova
country: Italy
facility: Ospedale San Martino
city: Lecce
country: Italy
facility: ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE
city: Messina
country: Italy
facility: Azienda Ospedaliera Papardo
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria - Policlinico G. Martino Dipartimento di Medicina Interna - U.O. Messina
city: Milano
country: Italy
facility: Ospedale Maggiore Policlinico
city: Modena
country: Italy
facility: Azienda Ospedaliera - Universitaria di Modena
city: Pescara
country: Italy
facility: U.O. Ematologia Clinica - Azienda USL di Pescara
city: Reggio Calabria
country: Italy
facility: Azienda Ospedaliera Bianchi Melacrino Morelli
city: Rome
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Tor Vergata
city: Rome
country: Italy
facility: Ospedale Sant' Eugenio
city: Rome
country: Italy
facility: Università Degli Studi "La Sapienza"
city: Rome
country: Italy
facility: Policlinico A. Gemelli - Universita Cattolica del Sacro Cuore
city: Siena
country: Italy
facility: U.O.C. Ematologia e Trapianti - A.O. Senese - Policlinico " Le Scotte"
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
city: Udine
country: Italy
facility: Policlinico Universitario Udine
Study officials:
affiliation: Universita Degli Studi "La Sapeinza"
name: Roberto Foa, MD
role: PRINCIPAL_INVESTIGATOR
References: