Combination Chemotherapy, Total-Body Irradiation, and Alemtuzumab in Treating Patients Undergoing an Autologous Stem Cell Transplant for Stage I, Stage II, Stage III, or Stage IV Chronic Lymphocytic Leukemia

September 23, 2016 updated by: German CLL Study Group

Campath 1H (Alemtuzumab) Combined With High-Dose Therapy and Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia

RATIONALE: Giving combination chemotherapy before a peripheral blood 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. A monoclonal antibody, such as alemtuzumab, is given to kill any remaining cancer cells. Chemotherapy and radiation therapy (total-body irradiation) are 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. Giving combination chemotherapy, total-body irradiation, and alemtuzumab together with autologous peripheral stem cell transplant may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with total-body irradiation and alemtuzumab works in treating patients undergoing an autologous stem cell transplant for stage I, stage II, stage III, or stage IV chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Chronic Lymphocytic Leukemia

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

Determine the safety and feasibility of cytoreductive fludarabine and cyclophosphamide followed by high-dose myeloablative therapy comprising total-body irradiation, cyclophosphamide, and alemtuzumab in patients undergoing autologous filgrastim (G-CSF)-mobilized peripheral blood stem cell transplantation for stage I-IV chronic lymphocytic leukemia.

Secondary

Determine the clinical and molecular remission rate and duration in patients treated with this regimen.
Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter, open label, nonrandomized study. Patients are assigned to 1 of 2 cohorts according to time of enrollment.

Cytoreductive induction therapy: All patients receive fludarabine IV and cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for 2-4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) or partial response (PR) proceed to stem cell mobilization. Patients with stage III or IV disease at this point are removed from study.
Stem cell mobilization: All patients receive Dexa-BEAM comprising oral dexamethasone once daily on days 1-10; carmustine IV and melphalan IV on day 2; and cytarabine IV twice daily and etoposide IV once daily on days 4-7. Patients also receive filgrastim (G-CSF) subcutaneously beginning on day 8 and continuing until leukapheresis is completed. Patients undergo peripheral blood stem cell (PBSC) harvest between days 20 and 28. Patients without an adequate number of collected PBSCs may receive a second course of Dexa-BEAM. Patients achieving CR or very good PR proceed to high-dose myeloablative therapy and PBSC transplantation (PBSCT) with or without consolidation therapy.
Consolidation therapy: Beginning between 1-2 months after completion of Dexa-BEAM, patients in cohort 2 receive alemtuzumab IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 and then proceed to high-dose myeloablative therapy and PBSCT within 1 month after completion of consolidation therapy. Patients in cohort 1 do not receive consolidation therapy and proceed directly to high-dose therapy within 3 months after completion of stem cell mobilization.
High-dose myeloablative therapy and PBSCT: Patients undergo total-body irradiation on days -7 to -5. Patients then receive cyclophosphamide IV on days -4 and -3 and alemtuzumab IV over 2 hours on days -10, -9, -8, -6, and -4. Patients undergo PBSCT on day 0.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Germany
- - Berlin, Germany, D-12200
    - Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin
  - Essen, Germany, D-45122
    - Universitaetsklinikum Essen
  - Hamburg, Germany, D-20099
    - Asklepios Klinik St. Georg
  - Hannover, Germany, D-30625
    - Medizinische Hochschule Hannover
  - Heidelberg, Germany, D-69120
    - Universitätsklinikum Heidelberg
  - Karlsruhe, Germany, 76133
    - Staedtisches Klinikum Karlsruhe gGmbH
  - Kiel, Germany, D-24105
    - University Hospital Schleswig-Holstein - Kiel Campus
  - Magdeburg, Germany, D-39120
    - Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
  - Mainz, Germany, 55101
    - Universitatsklinik Mainz
  - Munich, Germany, D-81377
    - Klinikum der Universitaet Muenchen - Grosshadern Campus
  - Munich, Germany, D-81675
    - Klinikum Rechts der Isar - Technische Universitaet Muenchen
  - Ulm, Germany, D-89081
    - Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

Chronic lymphocytic leukemia (CLL), meeting 1 of the following stage criteria:
- Stage I-IV disease
- Binet stage B or C disease
- Binet stage A disease at high risk for rapid disease progression, as defined by both of the following criteria:
  - Nonnodular marrow infiltration and/or lymphocyte doubling time < 12 months
  - Thymidine kinase > 7.0 U/L and/or ß-2-microglobulin > 3.5 mg/L
Polymerase chain reaction-amplifiable clonal CDR III rearrangement of the immunoglobulin variable heavy chain gene
No Richter's syndrome or B-prolymphocytic leukemia

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
No concurrent disease resulting in major organ dysfunction
Not pregnant or nursing
Fertile patients must use effective contraception
No other concurrent malignancy
No New York Heart Association class III or IV cardiac failure
No cardiomyopathy
No history of myocardial infarction
No symptomatic coronary heart disease
No severe cardiac arrhythmia
No severe or uncontrolled hypertension
No chronic pulmonary disease
No pulmonary function test impairment
No severe or uncontrolled diabetes mellitus
Bilirubin or transaminases ≤ 1.5 times upper limit of normal
Creatinine ≤ 1.4 mg/dL
No cerebral dysfunction
No severe psychiatric impairment
No drug addiction or alcoholism
Negative HIV
Negative Hepatitis B or C
No allergy to any of the protocol drugs
No history of anaphylactic reaction to monoclonal antibodies
No active infection

PRIOR CONCURRENT THERAPY:

No more than 1 prior chemotherapy regimen OR chemotherapy that lasted > 6 months
No prior radiotherapy
No prior treatment with alemtuzumab
No prior long-term (> 1 month) systemic corticosteroids
No prior therapy with dexamethasone, carmustine, etoposide, cytarabine, and melphalan (Dexa-BEAM)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and feasibility of CAMPATH-1H included into the myeloablative regimen (cyclophosphamide and TBI) of the CLL3 protocol monitoring of treatment related mortality and morbidity (CTC scale) continuous

Secondary Outcome Measures

Outcome Measure
Rate and duration of molecular responses MRD levels continuous
Rate and duration of clinical remissions NCIE sponsored remission criteria for CLL continuous
Overall survival time from treatment to death continuous

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

German CLL Study Group

Investigators

Study Chair: Stephan Stilgenbauer, MD, Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

German CLL Study Group

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2001

Primary Completion (Actual)

September 1, 2004

Study Completion (Actual)

September 1, 2004

Study Registration Dates

First Submitted

January 12, 2006

First Submitted That Met QC Criteria

January 12, 2006

First Posted (Estimate)

January 13, 2006

Study Record Updates

Last Update Posted (Estimate)

September 26, 2016

Last Update Submitted That Met QC Criteria

September 23, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

CLL3C
EU-20556
MEDAC-GCLLSG-CLL3C

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