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

Phase 2

Completed

• Conditions: Chronic Lymphocytic Leukemia
• Interventions: Biological: filgrastim; Drug: carmustine; Drug: cyclophosphamide; Drug: cytarabine; Drug: dexamethasone; Drug: etoposide; Drug: fludarabine phosphate; Drug: melphalan; Procedure: bone marrow ablation with stem cell support; Procedure: peripheral blood stem cell transplantation; Radiation: radiation therapy

• Registration Number: NCT00275015
• Lead Sponsor: German CLL Study Group

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 1998-01
• Study First Submitted: 2006-01-10
• Study First Submitted QC: 2006-01-10
• Study First Posted: 2006-01-11
• Study Completion: 2012-04
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-09
• Last Update Posted: 2018-05-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 169

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
High dose therapy + autologous PBSCT	filgrastim	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)
High dose therapy + autologous PBSCT	carmustine	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)
High dose therapy + autologous PBSCT	cyclophosphamide	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)
High dose therapy + autologous PBSCT	cytarabine	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)
High dose therapy + autologous PBSCT	dexamethasone	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)
High dose therapy + autologous PBSCT	etoposide	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)
High dose therapy + autologous PBSCT	fludarabine phosphate	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)
High dose therapy + autologous PBSCT	bone marrow ablation with stem cell support	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)
High dose therapy + autologous PBSCT	melphalan	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)
High dose therapy + autologous PBSCT	peripheral blood stem cell transplantation	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)
High dose therapy + autologous PBSCT	radiation therapy	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)

Primary Outcome Measures

Name	Time	Method
Safety of autologous peripheral stem cell transplantation (PBSCT) as measured by a treatment-related mortality of < 5% at 12 months following transplant
Feasibility of PBSCT as measured by > 50% of included patients proceeding to transplant

Secondary Outcome Measures

Name	Time	Method
Safety of mobilization comprising dexamethasone, carmustine, cytarabine, etoposide, and melphalan (Dexa-BEAM) as measured by a treatment-related mortality of < 5% before transplant phase
Efficacy of Dexa-BEAM mobilization as measured by the amount of CD34+ cells > 4x10e6/kg at harvest
Complete clinical remissions by NIH criteria at 3 months following transplant
Molecular remissions by CDR3 PCR at 3 months following transplant
Progression-free survival by NIH criteria at 5 years from study entry

Trial Locations

Locations (53)

Hanuschkrankenhaus; 🇦🇹 Vienna, Austria

Allg. Krankenhaus der Stadt Wien Universitaets-Kinderklinik; 🇦🇹 Wien, Austria

Humaine - Clinic; 🇩🇪 Bad Saarow, Germany

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin; 🇩🇪 Berlin, Germany

Robert Roessle Comprehensive Cancer Center at University of Berlin - Charite Campus Buch; 🇩🇪 Berlin, Germany

Universitaetsklinikum Bonn; 🇩🇪 Bonn, Germany

Praxis Dres. F.& G. Doering; 🇩🇪 Bremen, Germany

Universitatsklinikum Carl Gustav Carus; 🇩🇪 Dresden, Germany

Universitaetsklinikum Duesseldorf; 🇩🇪 Duesseldorf, Germany

Michael Schaefers und Partner; 🇩🇪 Duisburg, Germany

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