Know Cancer

or
forgot password

Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - a Multi-Center Trial


Phase 2
21 Years
N/A
Open (Enrolling)
Both
B-cell Chronic Lymphocytic Leukemia, Contiguous Stage II Small Lymphocytic Lymphoma, Noncontiguous Stage II Small Lymphocytic Lymphoma, Prolymphocytic Leukemia, Recurrent Small Lymphocytic Lymphoma, Refractory Chronic Lymphocytic Leukemia, Stage I Chronic Lymphocytic Leukemia, Stage I Small Lymphocytic Lymphoma, Stage II Chronic Lymphocytic Leukemia, Stage III Chronic Lymphocytic Leukemia, Stage III Small Lymphocytic Lymphoma, Stage IV Chronic Lymphocytic Leukemia, Stage IV Small Lymphocytic Lymphoma

Thank you

Trial Information

Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning for Patients With Chronic Lymphocytic Leukemia - a Multi-Center Trial


PRIMARY OBJECTIVES:

I. To determine whether nonmyeloablative allogeneic hematopoietic stem cell transplantation
(HSCT) from matched-related donors can improve the probability of survival 18 months after
treatment for fludarabine (fludarabine phosphate)-refractory, fludarabine phosphate,
cyclophosphamide, and rituximab (FCR)-failed, or del 17p chronic lymphocytic leukemia (CLL)
beyond that observed in historical controls (30%).

SECONDARY OBJECTIVES:

I. To assess the rate of relapse with allogeneic HSCT using nonmyeloablative conditioning
for patients with fludarabine-refractory, FCR-failed, or del 17p CLL compared with
historical data on autologous HSCT.

II. To estimate the incidence of grade 2-4 acute graft-versus-host disease (GVHD) and
chronic GVHD in patients with CLL treated with low-dose TBI, fludarabine, PBSC infusion and
immunosuppression with cyclosporine and mycophenylate mofetil.

III. To characterize the rate and types of infections with this regimen. IV. To estimate the
rate of transplant-related mortality in the first 200 days.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) on
days -4 to -2 and TBI on day 0.

TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive cyclosporine orally (PO) every 12 hours on days -3 to 180
with taper on day 56 and mycophenolate mofetil PO every 12 hours on days 0-27.

After completion of study treatment, patients are followed up at 12 and 18 months, and then
annually thereafter for 5 years.


Inclusion Criteria:



- Patients with CLL (or small lymphocytic lymphoma) or diagnosis of CLL that progresses
to prolymphocytic leukemia (PLL), or T-cell CLL or PLL

- Patients with B-Cell CLL or PLL who has at least one of the following:

- Failed to meet National Cancer Institute (NCI) Working Group criteria for complete or
partial response after therapy with a regimen containing fludarabine (or another
nucleoside analog, e.g. 2-CDA, pentostatin) or experience 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

- Had de novo of acquired "17p deletion" cytogenetic abnormality; patients should have
received induction chemotherapy but could be transplanted in 1st complete response
(CR)

- Patient has a suitable human leukocyte antigen (HLA)-matched related donor who is
willing to undergo leukapheresis initially for collection of peripheral blood stem
cells (PBSC) and subsequently for collection of peripheral blood mononuclear cells
(PBMC) with G-CSF mobilization and willing to donate stem cells

- DONOR: Related donor who is HLA phenotypically or genotypically identical at the
allele level at HLA-A, -B, -C, -DRB1, and -DQB1

- DONOR: Donor must consent to G-CSF administration and leukapheresis

- DONOR: Donor must have adequate veins for leukapheresis or agree to placement of
central venous catheter (femoral, subclavian)

Exclusion Criteria:

- Infection with human immunodeficiency virus (HIV), human T-lymphotropic virus
(HTLV)-1, or HTLV-2

- Active central nervous system (CNS) involvement with CLL

- Patients with active non-hematologic malignancies (except non-melanoma skin cancers)

- Patients with a history of non-hematologic malignancies (except non-melanoma skin
cancers) currently in a complete remission, who are less than 5 years from the time
of complete remission, and have a > 20% risk of disease recurrence

- Fertile men or women unwilling to use contraceptive techniques during and for 12
months following treatment

- Pregnant or breastfeeding women

- Karnofsky score =< 70

- Fungal infections with radiological progression after receipt of amphotericin B or
active triazole for greater than 1 month

- Cytotoxic agents for "cytoreduction" (with the exception of Gleevac, cytokine
therapy, hydroxyurea, chlorambucil or rituxan) within three weeks of the initiation
of conditioning

- Active bacterial or fungal infections unresponsive to medical therapy

- Cardiovascular: cardiac ejection fraction < 40%; patients with poorly controlled
hypertension despite multiple antihypertensives

- Pulmonary: diffusing capacity of carbon monoxide (DLCO) < 40%, total lung capacity
(TLC) <40%, forced expiratory volume in one second (FEV1) < 40% and/or requiring
continuous supplementary oxygen, or severe deficits in pulmonary function testing as
defined by pulmonary consultant service

- Liver function abnormalities: patients with clinical or laboratory evidence of liver
disease would be evaluated for the cause of liver disease, its clinical severity in
terms of liver function, bridging fibrosis, and the degree of portal hypertension;
patients will be excluded if they are found to have fulminant liver failure,
cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis,
esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy,
uncorrectable hepatic synthetic dysfunction evinced by prolongation of the
prothrombin time, ascites related to portal hypertension, bacterial or fungal liver
abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >
3mg/dL, or symptomatic biliary disease

- DONOR: Age < 12 years

- DONOR: Identical twin

- DONOR: Pregnancy

- DONOR: Infection with HIV

- DONOR: Inability to achieve adequate venous access

- DONOR: Known allergy to filgrastin (G-CSF)

- DONOR: Current serious systemic illness

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival using a non-myeloablative conditioning regimen with HSCT in patients with fludarabine phosphate-refractory CLL

Outcome Time Frame:

At 18 months

Safety Issue:

No

Principal Investigator

David Maloney

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

1711.00

NCT ID:

NCT00060424

Start Date:

March 2003

Completion Date:

Related Keywords:

  • B-cell Chronic Lymphocytic Leukemia
  • Contiguous Stage II Small Lymphocytic Lymphoma
  • Noncontiguous Stage II Small Lymphocytic Lymphoma
  • Prolymphocytic Leukemia
  • Recurrent Small Lymphocytic Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
  • Stage I Chronic Lymphocytic Leukemia
  • Stage I Small Lymphocytic Lymphoma
  • Stage II Chronic Lymphocytic Leukemia
  • Stage III Chronic Lymphocytic Leukemia
  • Stage III Small Lymphocytic Lymphoma
  • Stage IV Chronic Lymphocytic Leukemia
  • Stage IV Small Lymphocytic Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Prolymphocytic
  • Lymphoma

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
Veterans Administration Center-SeattleSeattle, Washington  98108