Cyclophosphamide and Total Body Irradiation in Treating Patients Who Are Undergoing an Autologous Peripheral Stem Cell Transplant For Chronic Lymphocytic Leukemia

German CLL Study Group

Status and phase

Completed

Phase 2

Conditions

Chronic Lymphocytic Leukemia

Treatments

Drug: dexamethasone

Drug: fludarabine phosphate

Procedure: peripheral blood stem cell transplantation

Drug: cyclophosphamide

Drug: cytarabine

Radiation: radiation therapy

Biological: filgrastim

Drug: etoposide

Procedure: bone marrow ablation with stem cell support

Drug: melphalan

Drug: carmustine

Study type

Interventional

Funder types

Other

Identifiers

NCT00275015

CLL3

EU-20553

Details and patient eligibility

About

RATIONALE: Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as G-CSF, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an peripheral stem cell transplant for chronic lymphocytic leukemia.

Full description

OBJECTIVES:

Primary

Determine the safety and feasibility of autologous peripheral blood stem cell transplantation in patients with chronic lymphocytic leukemia treated with cyclophosphamide and total-body irradiation.

Secondary

Determine the safety, feasibility, and efficacy of combination therapy comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) and filgrastim (G-CSF) mobilization in patients treated with this regimen.
Determine the efficacy of ex-vivo graft purging in patients treated with this regimen.
Determine the incidence of complete clinical and molecular remissions in patients treated with this regimen.
Determine the progression-free survival of patients treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized study.

Cytoreductive treatment: Patients undergo 2-4 courses of cytoreductive treatment, preferably following the fludarabine and cyclophosphamide (FC) protocol.
Stem cell mobilization: Patients achieving a complete remission (CR) or partial remission (PR) and stable blood counts undergo stem cell mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, melphalan (Dexa-BEAM), and filgrastim (G-CSF). Patients with an adequate number of mobilized cells undergo stem cell collection. Patients with CR or very good PR proceed to myeloablative therapy.
Myeloablative therapy: Patients undergo total-body irradiation on day -4 and receive cyclophosphamide IV on days -4 and -3.
Autologous peripheral blood stem cell transplantation (PBSCT): Patients undergo autologous PBSCT on day 0.

After completion of study, patients are followed periodically.

PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.

Enrollment

169 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Patients with chronic lymphocytic leukemia, meeting 1 of the following criteria:
- Binet stage B or C disease
- Binet stage A disease and at high risk for disease progression, defined as the following:
  - Non-nodular marrow infiltration or lymphocyte doubling time < 12 months
  - Thymidine kinase > 7.0 U/L or ß-2-microglobulin > 3.5 mg/L
Polymerase chain reaction-amplifiable clonal CDRIII rearrangement of the IgV_H

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
No concurrent disease resulting in major organ dysfunction

PRIOR CONCURRENT THERAPY:

No prior combination therapy comprising melphalan, dexamethasone, carmustine, cytarabine, and etoposide (DEXA-Beam)
No more than 1 prior chemotherapy regimen
No prior chemotherapy regimen longer than 6 months in duration

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

169 participants in 1 patient group

High dose therapy + autologous PBSCT

Experimental group

Description:

1. Cytoreductive treatment: (preferentially) FC (2-4 cycles) 2. Mobilization: Dexa-BEAM + G-CSF (1-2 cycles) 3. Myeloablation: fractionated TBI (e.g. 6x2Gy) + Cyclophosphamide (2 x 60 mg/kg; d -4 to -3) 4. autologous peripheral blood stem cell transplantation (PBSCT) (d 0)

Treatment: