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

July 15, 2016 updated by: Cancer and Leukemia Group B

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

47

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92093-0658
        • Rebecca and John Moores UCSD Cancer Center
      • San Diego, California, United States, 92161
        • Veterans Affairs Medical Center - San Diego
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center
    • Delaware
      • Lewes, Delaware, United States, 19958
        • Beebe Medical Center
      • Newark, Delaware, United States, 19713
        • CCOP - Christiana Care Health Services
      • Wilmington, Delaware, United States, 19805
        • St. Francis Hospital
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Holden Comprehensive Cancer Center at University of Iowa
    • Maryland
      • Elkton MD, Maryland, United States, 21921
        • Union Hospital Cancer Center at Union Hospital
    • Massachusetts
      • Worcester, Massachusetts, United States, 01655
        • UMASS Memorial Cancer Center - University Campus
    • New Jersey
      • Voorhees, New Jersey, United States, 08043
        • Cancer Institute of New Jersey at the Cooper University Hospital - Voorhees
    • New York
      • Buffalo, New York, United States, 14263-0001
        • Roswell Park Cancer Institute
      • Elmhurst, New York, United States, 11373
        • Elmhurst Hospital Center
      • Jamaica, New York, United States, 11432
        • Queens Cancer Center of Queens Hospital
      • New York, New York, United States, 10029
        • Mount Sinai Medical Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7295
        • Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
      • Winston-Salem, North Carolina, United States, 27157-1096
        • Wake Forest University Comprehensive Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210-1240
        • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224-1791
        • Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Massey Cancer Center at Virginia Commonwealth University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 69 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allogeneic Stem Cell Tx
minimal ablation and cellular immune therapy with allogeneic donor stem cell therapy
Drug: fludarabine phosphate
30 mg/sq m/day IV infusion for 5 days (Days -7 thru -3)
Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Treatment-related mortality within the first 6 months post-transplant
Time Frame: 6 months post chemo initiation
6 months post chemo initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response
Time Frame: 6 months & 12 months
6 months & 12 months
Percentage of patients achieving complete donor chimerism or mixed donor chimerism
Time Frame: 90 days post transplant
90 days post transplant
Survival
Time Frame: 5 years post study entry
Disease free and overall survival will be assessed
5 years post study entry

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cancer and Leukemia Group B

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Thomas Shea, MD, UNC Lineberger Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2001

Primary Completion (Actual)

January 1, 2007

Study Completion (Actual)

October 1, 2011

Study Registration Dates

First Submitted

September 11, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimate)

January 27, 2003

Study Record Updates

Last Update Posted (Estimate)

July 18, 2016

Last Update Submitted That Met QC Criteria

July 15, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CALGB-109901
  • U10CA031946 (U.S. NIH Grant/Contract)
  • CDR0000068185 (Registry Identifier: NCI Physician Data Query)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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