Low-Dose Chemotherapy and Radiation Therapy Before Donor Stem Cell Transplant in Treating Patients With Refractory Chronic Lymphocytic Leukemia - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00060424

Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine, and radiation therapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving low-dose fludarabine and total-body irradiation before donor stem cell transplant works in treating patients with refractory chronic lymphocytic leukemia.

Condition	Intervention	Phase
Leukemia	Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - A Multi-Center Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Fludarabine Cyclosporine Fludarabine monophosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate Mofetil

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Survival at 18 months [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rate of relapse [ Designated as safety issue: No ]
Incidence of grade II-IV acute graft-versus-host disease (GVHD) [ Designated as safety issue: Yes ]
Incidence of grade II-IV chronic GVHD [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	March 2003
Estimated Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Compare the 18-month survival rate of patients with fludarabine-refractory chronic lymphocytic leukemia treated with nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) from matched-related donors with that observed in historical controls.

Secondary

Compare the rate of relapse in patients treated with this regimen with that of historical controls.
Determine the incidence of grade 2-4 acute and chronic graft-versus-host disease in patients treated with low-dose total body irradiation, fludarabine, peripheral blood stem cell infusion, and immunosuppression with cyclosporine and mycophenolate mofetil.
Determine the rate and types of infections in patients treated with this regimen.
Determine the rate of transplant-related mortality in the first 200 days in patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients may receive cytoreductive therapy before beginning treatment.

Conditioning regimen: Patients receive fludarabine IV on days -4 to -2. Patients then undergo total body irradiation (TBI) on day 0.
Allogeneic stem cell transplantation: After TBI, patients undergo hematopoietic stem cell infusion on day 0.
Immunosuppression: Patients receive oral cyclosporine twice daily on days -3 to 180 (with tapering beginning on day 56 in the absence of graft-versus-host disease [GVHD]). Patients also receive oral mycophenolate mofetil twice daily on days 0-27 (may continue if GVHD occurs).
Donor lymphocyte infusion (DLI): Post transplant DLI may given on a separate DLI protocol or treatment plan.

After completion of study treatment, patients are followed at 6, 12, and 18 months, and then annually for 3 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 3 years.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of chronic lymphocytic leukemia (CLL) defined by the following criteria:
- Absolute peripheral lymphocytosis greater than 5,000/mm^3 that persisted for at least 4 weeks
- Mature lymphocytes with less than 55% cells comprising atypical lymphocytes, prolymphocytes, or lymphoblasts in peripheral blood
- Normal cellular or hypercellular bone marrow aspirate and biopsy with greater than 30% of the nucleated cells of lymphoid origin
- Flow cytometric evidence of more than one B-cell marker (CD19, CD20, or CD23) plus CD5 in peripheral blood or bone marrow
CLL that progresses to prolymphocytic leukemia (PLL) and CLL/small lymphocytic lymphoma is allowed
Patients with B-Cell CLL or PLL meeting the following criteria:
- Failure to meet NCI Working Group criteria for complete or partial response after therapy with a regimen containing fludarabine (or another nucleoside analog [e.g., cladribine or pentostatin]) or disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)
- Failed FCR combination chemotherapy at any time point
- De novo of acquired "17p deletion" cytogenetic abnormality
Availability of a suitable HLA-matched related donor
- Related donor who is phenotypically or genotypically identical at the allele level at HLA-A, -B, -C, -DRB1, and -DQB1
- No identical twins
No active CNS involvement

PATIENT CHARACTERISTICS:

Age

21 and over

Performance status

Karnofsky 70-100%

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

No chronic viral hepatitis with total serum bilirubin > 3 mg/dL
No alcoholic hepatitis
No bacterial or fungal liver abscess
No ascites related to portal hypertension
No cirrhosis with evidence of portal hypertension
No uncorrectable hepatic synthetic dysfunction as evidenced by PT prolongation
No fulminant liver failure
No hepatic encephalopathy
No biliary obstruction
No symptomatic biliary disease

Renal

Not specified

Cardiovascular

Cardiac ejection fraction at least 40%
No poorly controlled hypertension despite antihypertensive therapy

Pulmonary

DLCO at least 40%
Total lung capacity at least 40%
FEV1 at least 40%
No requirement for continuous supplementary oxygen
No severe deficits in pulmonary function

Other

Not pregnant or nursing
Fertile patients must use effective contraception during and for 12 months after study treatment
No esophageal varices OR history of bleeding esophageal varices
HIV negative
HTLV-1 and HTLV-2 negative
No active bacterial infection unresponsive to medication
No fungal infection with radiological progression unresponsive to amphotericin B or active triazole for > 1 month
No other non-hematologic malignancy within the past 5 years except nonmelanoma skin cancer
- Patients with a history of cancer more than 5 years ago must have ≤ 20% chance of recurrence

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent growth factors during mycophenolate mofetil administration

Chemotherapy

See Disease Characteristics
More than 3 weeks since cytotoxic agents for cytoreduction except imatinib mesylate, cytokine therapy, hydroxyurea, chlorambucil, or rituxan

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00060424

Locations

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109-1024
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Veterans Affairs Medical Center - Seattle
Seattle, Washington, United States, 98108
Italy
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, Italy, 10126

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

David G. Maloney, MD, PhD

Fred Hutchinson Cancer Research Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Fred Hutchinson Cancer Research Center ( David G. Maloney )
Study ID Numbers:	CDR0000301894, FHCRC-1711.00
Study First Received:	May 6, 2003
Last Updated:	July 17, 2009
ClinicalTrials.gov Identifier:	NCT00060424 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

refractory chronic lymphocytic leukemia

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Leukemia, Lymphoid
Vidarabine
Antimetabolites, Antineoplastic
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Mycophenolic Acid
Antibiotics, Antineoplastic
Cyclosporins
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell

Therapeutic Uses
Antifungal Agents
Mycophenolate mofetil
Dermatologic Agents
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine

ClinicalTrials.gov processed this record on November 27, 2009