Fludarabine and Cyclophosphamide Followed by Peripheral Stem Cell Transplant in Treating Patients With Leukemia or Lymphoma

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00006252
• Other study ID #: CALGB-109901
• Secondary ID: U10CA031946CALGB
• Status: Completed
• Phase: Phase 2
• First received: September 11, 2000
• Last updated: July 15, 2016
• Start date: February 2001
• Est. completion date: October 2011

Study information

• Verified date: July 2016
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: October 2011
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 69 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Prolymphocytic
• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• fludarabine phosphate
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
• Cyclophosphamide
1 g/sq m/day IV infusion x 3 days (Days -5 thru -3)

Biological:
• PBSC
2-8,000,000/kg CD34+ cells via infusion on Day 0

Drug:
• G-CSF
5 ug/kg/day subQ injection until ANC > 1000/uL for 3 days beginning Day 5

Biological:
• Donor lymphocytes
10,000,000 CD3+ cells/kg via infusion

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina
United States	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University	Columbus	Ohio
United States	Union Hospital Cancer Center at Union Hospital	Elkton MD	Maryland
United States	Elmhurst Hospital Center	Elmhurst	New York
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa
United States	Queens Cancer Center of Queens Hospital	Jamaica	New York
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Beebe Medical Center	Lewes	Delaware
United States	Mount Sinai Medical Center	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Massey Cancer Center at Virginia Commonwealth University	Richmond	Virginia
United States	Veterans Affairs Medical Center - San Diego	San Diego	California
United States	UCSF Comprehensive Cancer Center	San Francisco	California
United States	Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees	Voorhees	New Jersey
United States	St. Francis Hospital	Wilmington	Delaware
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Cancer and Leukemia Group B	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Shea TC, Johnston J, Walsh W, et al.: Reduced intensity allogeneic transplantation provides high disease-free and overall survival in patients (pts) with advanced indolent NHL and CLL: CALGB 109901. [Abstract] Blood 110 (11): A-486, 2007.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality within the first 6 months post-transplant		6 months post chemo initiation	Yes
Secondary	Response		6 months & 12 months	No
Secondary	Percentage of patients achieving complete donor chimerism or mixed donor chimerism		90 days post transplant	No
Secondary	Survival	Disease free and overall survival will be assessed	5 years post study entry	No