Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Active 21 and over NCI FHCRC-1711.00 NCT00060424

Objectives

Primary

1. 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

1. Compare the rate of relapse in patients treated with this regimen with that of historical controls.
2. 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.
3. Determine the rate and types of infections in patients treated with this regimen.
4. Determine the rate of transplant-related mortality in the first 200 days in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of chronic lymphocytic leukemia (CLL) defined by the following criteria:
  • Absolute peripheral lymphocytosis greater than 5,000/mm³ 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 and CLL/small lymphocytic lymphoma is allowed



• Refractory disease by one of 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])
  • Disease relapse within 12 months after completing therapy with a regimen containing fludarabine (or another nucleoside analog)



• 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

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

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

Expected Enrollment

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

Outcomes

Survival at 18 months

Rate of relapse
Incidence of grade II-IV acute graft-versus-host disease (GVHD)
Incidence of grade II-IV chronic GVHD

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

David Maloney, MD, PhD, Protocol chair		Ph: 206-667-5616 Email: dmaloney@fhcrc.org

U.S.A.
Washington
	Seattle
	Fred Hutchinson Cancer Research Center
		David Maloney, MD, PhD	Ph:  206-667-5616
			Email: dmaloney@fhcrc.org
	Seattle Cancer Care Alliance
		Clinical Trials Office - Seattle Cancer Care Alliance	Ph:  800-804-8824
	Veterans Affairs Medical Center - Seattle
		Thomas R. Chauncey, MD, PhD	Ph:  206-762-1010
Italy
	Turin
	Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
		Benedetto Bruno, MD, PhD	Ph:  39-339-112-9064
			Email: benedetto.bruno@unito.it

Registry Information
Official Title		Allogeneic Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning for Patients with Chronic Lymphocytic Leukemia - A Multi-Center Trial
Trial Start Date		2003-03-20
Trial Completion Date		2008-03-20 (estimated)
Registered in ClinicalTrials.gov		NCT00060424
Date Submitted to PDQ		2003-04-04
Information Last Verified		2008-09-22
NCI Grant/Contract Number		CA78902, HL36444 , CA15704

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