NCT00001586

Brief Summary

Background:

  • Combined therapy with rituximab and fludarabine is the treatment of choice for advanced stage chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
  • A new technology called deoxyribonucleic acid (DNA) microarray can be used to gain knowledge about the genetic basis of CLL/SLL.
  • Genetic studies of CLL/SLL may improve our understanding of what happens in the disease, help determine which patients are most likely to respond to treatment with fludarabine and rituximab, and identify new treatments. Objectives:
  • To gain further knowledge about CLL/SLL and the role of rituximab and fludarabine in treating the disease. Eligibility:
  • Patients 18 years of age and older with low, intermediate or high-risk CLL/SLL. Design:
  • Patients with low-risk CLL/SLL do not receive treatment, but are followed every 3 to 6 months and donate cells (through apheresis) or lymph nodes, or both, for research purposes.
  • Patients with intermediate or high-risk CLL/SLL receive standard treatment with rituximab and fludarabine for six 28-day treatment cycles. Rituximab is given on day 1 and fludarabine is given on days 1-5. (For the first cycle only, fludarabine treatment starts on day 2. This delay permits blood sampling on day 1 for the effect of rituximab on white blood cells.)
  • Laboratory tests and imaging studies are done periodically to monitor drug side effects and the response to treatment. Tests include bone marrow biopsy and aspiration, blood tests and x-rays, including positron emission tomography (PET) and computed tomography (CT) scans.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
105

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Sep 1997

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 1997

Completed
2.2 years until next milestone

First Submitted

Initial submission to the registry

November 3, 1999

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 4, 1999

Completed
12 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2011

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2011

Completed
1.5 years until next milestone

Results Posted

Study results publicly available

May 15, 2013

Completed
Last Updated

May 15, 2013

Status Verified

March 1, 2013

Enrollment Period

14.2 years

First QC Date

November 3, 1999

Results QC Date

December 18, 2012

Last Update Submit

March 19, 2013

Conditions

Chronic Lymphocytic Leukemia

Keywords

GeneticsBone Marrow TransplantationImmunosuppressionT LymphocytesMarrow Purging

Outcome Measures

Primary Outcomes (1)

  • Change in Gene Expression Post Chemo

    Changes in lymphocyte gene expression was measured by deoxyribonucleic acid (DNA) microarray analysis of circulating leukemic cells after completion of study treatment. A change in expression is defined as a \>50% increase in circulating leukemic cells or a 30% decrease in circulating leukemic cells.

    6 hours post treatment, and 24 hours post treatment

Secondary Outcomes (1)

  • Number of Participants With Adverse Events

    13 years, 10.5 months

Study Arms (2)

Low-Intermediate Risk B-Cell Pts

EXPERIMENTAL

Previously untreated low or intermediate risk B-cell chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) patients (pts) not requiring chemotherapy. No rituximab fludarabine administered. Eligible to donate cells.

Other: Leukemic or stroma cells

Intermediate-high Risk B-Cell Pts

EXPERIMENTAL

Previously untreated intermediate or high risk B-cell chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) patients requiring chemotherapy. Rituximab 375 mg/m\^2 by infusion on day 1, cycle 1 followed by fludarabine on day 2-6, 25 mg/m\^2 day x 5 days administered as an intravenous push or intravenous piggyback over 10-30 minutes, repeated every 28 days.

Biological: RituximabDrug: Fludarabine phosphate

Interventions

RituximabBIOLOGICAL

Rituxan

Also known as: Rituximab 375 mg/m^2 by infusion on day 1, cycle 1. Repeated every 28 days.
Intermediate-high Risk B-Cell Pts
Fludarabine phosphateDRUG

Fludara

Also known as: Fludarabine on day 2-6, 25 mg/m^2 day x 5 days administered as an intravenous push or intravenous piggyback over 10-30 minutes, repeated every 28 days.
Intermediate-high Risk B-Cell Pts
Leukemic or stroma cellsOTHER

Patients are eligible to donate cells for the purpose of analyzing leukemic cells. Cells can be donated by apheresis (e.g. 60-90 minute intravenous technique), lymph node biopsy (e.g. 3 biopsy/excision of lymph nodes)bone marrow biopsy (e.g. 2-4 separate bone marrow biopsies), and bone marrow aspiration (e.g. 3 to 5cc of marrow per aspirate).

Low-Intermediate Risk B-Cell Pts

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) will be made according to the World Health Organization (WHO) diagnostic classification. A lymphocyte count in excess of 5000/mcl is typically found in the leukemic variant but is not a pre-requisite for a diagnosis of SLL. Low, Intermediate or High-Risk Category of CLL/SLL, using the Modified Three-Stage Rai Staging System as follows:
  • Risk Category: Low Risk
  • Rai Stage: 0
  • Clinical Features: Elevated blood and marrow lymphocyte numbers only (L). (lymphocytes greater than 5000/microl in blood, and lymphocytes greater than 30 percent in marrow).
  • Risk Category: Intermediate Risk
  • Rai Stage: I
  • Clinical Features: L + enlarged lymph nodes (LN)
  • Risk Category: Intermediate Risk
  • Rai Stage: II
  • Clinical Features: L + enlarged spleen or liver
  • Risk Category: High Risk
  • Rai Stage: III
  • Clinical Features: L + anemia (Hemoglobin less than 11 gm/dl)
  • Risk Category: High Risk
  • Rai Stage: IV
  • +15 more criteria

You may not qualify if:

  • Patients must not be pregnant or breastfeeding.
  • Patients with active autoimmune hemolytic anemia (AIHA)) grade III or higher (transfusion or steroids indicated) or immune thrombocytopenia (ITP) grade III or higher (platelets less than 50,000/microL) shall not be enrolled. Patients with a history of prior therapy to control either AIHA or ITP will be eligible, provided they do not require maintenance corticosteroids, and have not received monoclonal antibody therapy in the past 6 months. Patients developing AIHA or ITP on protocol may be managed as medically indicated on protocol but will generally not undergo fludarabine/rituximab treatment until resolution of hemolysis or thrombocytopenia to less than grade III.
  • Any patient with a medical condition that requires chronic use of corticosteroids shall not be enrolled.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

  • Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975 Aug;46(2):219-34.

    PMID: 1139039BACKGROUND

  • Keating MJ. Fludarabine phosphate in the treatment of chronic lymphocytic leukemia. Semin Oncol. 1990 Oct;17(5 Suppl 8):49-62.

    PMID: 1699283BACKGROUND

  • Raife TJ, Demetroulis EM, Lentz SR. Regulation of thrombomodulin expression by all-trans retinoic acid and tumor necrosis factor-alpha: differential responses in keratinocytes and endothelial cells. Blood. 1996 Sep 15;88(6):2043-9.

    PMID: 8822923BACKGROUND

  • Mo CC, Njuguna N, Beum PV, Lindorfer MA, Vire B, Lee E, Marti G, Wilson WH, Taylor RP, Wiestner A. Rapid clearance of rituximab may contribute to the continued high incidence of autoimmune hematologic complications of chemoimmunotherapy for chronic lymphocytic leukemia. Haematologica. 2013 Aug;98(8):1259-63. doi: 10.3324/haematol.2012.080929. Epub 2013 May 28.

    PMID: 23716541DERIVED

  • Herishanu Y, Perez-Galan P, Liu D, Biancotto A, Pittaluga S, Vire B, Gibellini F, Njuguna N, Lee E, Stennett L, Raghavachari N, Liu P, McCoy JP, Raffeld M, Stetler-Stevenson M, Yuan C, Sherry R, Arthur DC, Maric I, White T, Marti GE, Munson P, Wilson WH, Wiestner A. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011 Jan 13;117(2):563-74. doi: 10.1182/blood-2010-05-284984. Epub 2010 Oct 12.

    PMID: 20940416DERIVED

Related Links

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Rituximabfludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Results Point of Contact

Title
Wyndham H. Wilson, M.D.
Organization
National Cancer Institute, National Institutes of Health
wilsonw@mail.nih.gov
301-435-2415

Study Officials

  • Wyndham H Wilson, M.D.

    National Cancer Institute, National Institutes of Health

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal investigator

Study Record Dates

First Submitted

November 3, 1999

First Posted

November 4, 1999

Study Start

September 1, 1997

Primary Completion

November 1, 2011

Study Completion

November 1, 2011

Last Updated

May 15, 2013

Results First Posted

May 15, 2013

Record last verified: 2013-03

Locations

US(1)