Clinical trial NCT00006252: Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 47
Sex: ALL
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well fludarabine and cyclophosphamide followed by peripheral stem cell transplant works in treating patients with leukemia or lymphoma.

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Treatment-related mortality within the first 6 months post-transplant
timeFrame: 6 months post chemo initiation
Secondary outcomes:
measure: Response
timeFrame: 6 months & 12 months
measure: Percentage of patients achieving complete donor chimerism or mixed donor chimerism
timeFrame: 90 days post transplant
measure: Survival
timeFrame: 5 years post study entry
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: San Diego
country: United States
facility: Veterans Affairs Medical Center - San Diego
state: California
city: San Francisco
country: United States
facility: UCSF Comprehensive Cancer Center
state: California
city: Lewes
country: United States
facility: Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Wilmington
country: United States
facility: St. Francis Hospital
state: Delaware
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Elkton MD
country: United States
facility: Union Hospital Cancer Center at Union Hospital
state: Maryland
city: Worcester
country: United States
facility: UMASS Memorial Cancer Center - University Campus
state: Massachusetts
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Elmhurst
country: United States
facility: Elmhurst Hospital Center
state: New York
city: Jamaica
country: United States
facility: Queens Cancer Center of Queens Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Richmond
country: United States
facility: Massey Cancer Center at Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: UNC Lineberger Comprehensive Cancer Center
name: Thomas Shea, MD
role: STUDY_CHAIR
References:
citation: Shea T, Johnson J, Westervelt P, Farag S, McCarty J, Bashey A, Isola L, Baxter-Lowe LA, Kelly M, Owzar K, Linker C; Cancer and Leukemia Group B. Reduced-intensity allogeneic transplantation provides high event-free and overall survival in patients with advanced indolent B cell malignancies: CALGB 109901. Biol Blood Marrow Transplant. 2011 Sep;17(9):1395-403. doi: 10.1016/j.bbmt.2011.01.016. Epub 2011 Feb 3.