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Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells


Phase 2
N/A
69 Years
Open (Enrolling)
Both
Leukemia, Lymphoma

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Trial Information

Minimal Ablation and Cellular Immune Therapy of Chronic Lymphocytic Leukemia, Prolymphocytic Leukemia, Low-Grade Non-Hodgkin's Lymphoma, and Mantle Cell Lymphoma With Allogeneic Donor Stem Cells


OBJECTIVES:

- Determine the feasibility of fludarabine and cyclophosphamide followed by allogeneic
peripheral blood stem cell transplantation, in terms of 6-month treatment-related
mortality, in patients with chronic lymphocytic leukemia, prolymphocytic leukemia,
low-grade non-Hodgkin's lymphoma, or mantle cell lymphoma.

- Determine the 6-month and 12-month probabilities of response in patients treated with
this regimen.

- Determine the time to disease progression in patients responding to this regimen.

- Determine the percentage of donor chimerism achieved in patients treated with this
regimen.

- Determine the risk of acute and chronic graft-versus-host disease in patients treated
with this regimen.

- Determine the toxic effects of this regimen in these patients.

- Determine the overall survival and disease-free survival of patients treated with this
regimen.

OUTLINE: This is a multicenter study.

Patients receive fludarabine IV over 30 minutes on days -7 to -3 and cyclophosphamide IV
over 1 to 2 hours on days -5 to -3. Patients undergo allogeneic peripheral blood stem cell
transplantation on days 0-1. Patients then receive filgrastim (G-CSF) subcutaneously daily
beginning on day 5 and continuing until blood counts recover.

Patients with no signs of active graft-versus host disease and stable or progressive disease
receive donor lymphocytes IV over 2 hours beginning after day 120. Patients may receive a
total of 3 infusions at least 8 weeks apart if disease remains stable or progressive.

Patients are followed every 3 months for 2 years and then every 6 months for 5 years.

PROJECTED ACCRUAL: A maximum of 45 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- One of the following histologically confirmed diagnoses:

- Chronic lymphocytic leukemia

- Absolute lymphocytosis greater than 5,000/mm^3

- Morphologically mature lymphocytes with less than 55% prolymphocytes

- Lymphocyte phenotypic expression of CD19 and CD5

- Failed at least 1 prior regimen

- Progressive lymphocytosis with more than 50% increase in peripheral
lymphocytosis or a progressive lymph node or spleen enlargement (at
least 25% enlargement or the appearance of new lymph nodes) that
persists for at least 4 weeks despite concurrent or prior drug
treatment OR

- At least 1 of the following high-risk factors and not in first complete
remission

= 17p deletion = 11q deletion

- Unmutated VH gene status

- p53 mutations

- Prolymphocytic leukemia (PLL)

- Absolute lymphocytosis greater than 5,000/mm^3

- Morphologically mature lymphocytes with more than 55% prolymphocytes

- Low-grade non-Hodgkin's lymphoma

- Small lymphocytic lymphoma

- Follicular center lymphoma (grade I or II)

- Diffuse (predominately small cell type)

- Marginal zone, B-cell lymphoma

- No transformed lymphoma

- Failure of at least 1 prior regimen OR

- At least 3 of the following risk factors:

- Over 60 years of age

- Performance status greater than 1

- LDH greater than normal

- More than 1 site of extranodal disease

- Disease stage III or IV

- Mantle cell lymphoma

- Any stage

- Ineligible for protocol CALGB-59908

- At least 1 prior treatment regimen

- At least 1 of the following:

- Immunophenotypic expression of CD5 and CD19 and absence of CD23

- Cytogenetic analysis with presence of t(11;14)

- Overexpression of cyclin D1

- Rearrangement of BCL1 gene

- Responsive or stable disease to most recent prior therapy

- Prior therapy for PLL not required

- Must have HLA identical sibling (6/6) donor by serologic typing (A, B, DR)

- No syngeneic donors

- No age restriction NOTE: A new classification scheme for adult
non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of
"indolent" or "aggressive" lymphoma will replace the former terminology of
"low", "intermediate", or "high" grade lymphoma. However, this protocol
uses the former terminology.

PATIENT CHARACTERISTICS:

Age:

- Under 70

Performance status:

- Not specified

Life expectancy:

- Not specified

Hematopoietic:

- Granulocyte count at least 500/mm^3*

- Platelet count at least 50,000/mm^3* NOTE: *Unless attributable to disease

Hepatic:

- Bilirubin no greater than 3 times upper limit of normal (ULN)*

- AST no greater than 3 times ULN* NOTE: *Unless attributable to disease

Renal:

- Creatinine clearance at least 40 mL/min, unless attributable to disease

Cardiovascular:

- LVEF at least 30% by MUGA

Pulmonary:

- DLCO greater than 40%

- No symptomatic pulmonary disease

Other:

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No uncontrolled diabetes mellitus

- No active serious infection

- No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- No prior autologous transplantation

Chemotherapy:

- At least 4 weeks since prior chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 4 weeks since prior radiotherapy

Surgery:

- At least 4 weeks since prior surgery

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Treatment-related mortality within the first 6 months post-transplant

Outcome Time Frame:

6 months post chemo initiation

Safety Issue:

Yes

Principal Investigator

Thomas C. Shea, MD

Investigator Role:

Study Chair

Investigator Affiliation:

UNC Lineberger Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CDR0000068185

NCT ID:

NCT00006252

Start Date:

February 2001

Completion Date:

October 2011

Related Keywords:

  • Leukemia
  • Lymphoma
  • refractory chronic lymphocytic leukemia
  • stage I grade 1 follicular lymphoma
  • stage I grade 2 follicular lymphoma
  • stage I adult diffuse small cleaved cell lymphoma
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • prolymphocytic leukemia
  • stage I mantle cell lymphoma
  • contiguous stage II grade 1 follicular lymphoma
  • contiguous stage II grade 2 follicular lymphoma
  • contiguous stage II adult diffuse small cleaved cell lymphoma
  • contiguous stage II mantle cell lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • stage III mantle cell lymphoma
  • stage IV mantle cell lymphoma
  • recurrent mantle cell lymphoma
  • contiguous stage II small lymphocytic lymphoma
  • contiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • stage I marginal zone lymphoma
  • stage I small lymphocytic lymphoma
  • stage III small lymphocytic lymphoma
  • stage III marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • stage IV marginal zone lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Leukemia, Prolymphocytic
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Mantle-Cell

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002
UMASS Memorial Cancer Center - University CampusWorcester, Massachusetts  01605-2982
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State UniversityColumbus, Ohio  43210-1240
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Veterans Affairs Medical Center - San DiegoSan Diego, California  92161
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Elmhurst Hospital CenterElmhurst, New York  11373
Queens Cancer Center of Queens HospitalJamaica, New York  11432
Mount Sinai Medical CenterNew York, New York  10029
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Massey Cancer Center at Virginia Commonwealth UniversityRichmond, Virginia  23298-0037
Cancer Institute of New Jersey at the Cooper University Hospital - VoorheesCamden, New Jersey  08103
Beebe Medical CenterLewes, Delaware  19958
St. Francis HospitalWilmington, Delaware  19805
Union Hospital Cancer Center at Union HospitalElkton MD, Maryland  21921
Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224-1791