Identifying Prognostic Factors in Frontline FCR for Patients With Chronic Lymphocytic Leukemia (CLL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00759798
First received: September 24, 2008
Last updated: May 7, 2014
Last verified: May 2014

September 24, 2008
May 7, 2014
August 2008
August 2016   (final data collection date for primary outcome measure)
Complete Remission Rate (CRR) [ Time Frame: After 6 months ] [ Designated as safety issue: No ]
CRR defined by NCI Working Group / International Working Group for CLL criteria as no evidence of disease on physical examination (no adenopathy or organomegaly) or microscopic examination of blood (ALC <4,000/L) and bone marrow (<30% lymphocytes, no lymphoid nodules), and recovery of hemoglobin, neutrophil, and platelet counts.
The primary objective of the study is to prospectively evaluate new and traditional prognostic factors and evaluate associations with complete remission (CR) in frontline patients treated with FCR. [ Time Frame: August 2013 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00759798 on ClinicalTrials.gov Archive Site
Not Provided
To prospectively evaluate new and traditional prognostic factors and evaluate associations with overall response and time to failure in frontline patients treated with FCR. [ Time Frame: August 2013 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Identifying Prognostic Factors in Frontline FCR for Patients With Chronic Lymphocytic Leukemia (CLL)
Prospective Identification of Significant Prognostic Factors in Patients Treated With Fludarabine, Cyclophosphamide, and Rituximab (FCR) as Initial Therapy for Chronic Lymphocytic Leukemia.

The goal of this clinical research study is to learn more about the characteristics of CLL, including genes and chromosome abnormalities and proteins expressed by the leukemia cells, which may help doctors predict if patients who receive standard treatment (fludarabine, cyclophosphamide, and rituximab) for the first time will experience a complete remission.

The Study Drugs:

Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.

Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth and spread throughout the body. This may cause the cancer cells to die.

Rituximab is designed to attach to lymphoma cells, which may cause them to die.

Study Drug Administration:

Each cycle is 4-6 weeks.

If you are found to be eligible to take part in this study, on Day 1 of each cycle, you will receive rituximab through a needle into your vein over 6-8 hours.

On Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond, you will receive fludarabine by vein over 30 minutes. You will also receive cyclophosphamide by vein over 30 minutes.

You will receive drugs (such as Tylenol, Benadryl, Zofran, allopurinol, and Valtrex) to help prevent side effects. If you have side effects while receiving rituximab, you may be monitored by the study staff for 2 hours after each dose.

Study Visits:

Once a week, blood (about 1 tablespoon) will be drawn for routine tests.

After 3 months (3 cycles of treatment), the following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests.
  • You will have a bone marrow aspirate and biopsy to check the status of the disease.

Length of Study:

You will be on treatment for about 6 months. You will be taken off treatment early if you have intolerable side effects or the disease gets worse.

End-of-Treatment Visit:

After you are off treatment, you will have an end-of-treatment visit for doctors to learn your overall response to the treatment. The following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests.
  • You will have a bone marrow aspirate and biopsy to check the status of the disease.

Long-Term Follow-up:

At 6 months after you have finished treatment and then every year from then on, you will have follow-up visits. The following tests and procedures will be performed:

  • You will have a physical exam.
  • Blood (about 2 tablespoons) will be drawn for routine tests.
  • If your doctor thinks it is needed, you will have a bone marrow biopsy and aspirate to check the status of the disease.

This is an investigational study. Fludarabine, cyclophosphamide, and rituximab are FDA approved and commercially available for the treatment of CLL. The correlation with response to treatment and the characteristics of the leukemia cells is investigational.

Up to 300 patients will take part in this study. All will be enrolled at MD Anderson.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia
  • Leukemia
  • Drug: Fludarabine
    25 mg/m^2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond.
    Other Name: Fludara®
  • Drug: Cyclophosphamide
    250 mg/m2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond.
    Other Names:
    • Cytoxan®
    • Neosar®
  • Drug: Rituximab

    375 mg/m2 given intravenously on Day 1 of Course 1

    All subsequent Courses: 500 mg/m2 given intravenously on Day 1 (Weeks 5,9,13,17,21)

    Other Name: Rituxan®
Experimental: Fludarabine, Cyclophosphamide, Rituximab

Fludarabine 25 mg/m^2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond. Cyclophosphamide 250 mg/m2 given intravenously on Days 2-4 of Cycle 1 and Days 1-3 of Cycles 2 and beyond. Rituximab 375 mg/m2 given intravenously on Day 1 of Course 1

All subsequent Courses: 500 mg/m2 given intravenously on Day 1 (Weeks 5,9,13,17,21)

Interventions:
  • Drug: Fludarabine
  • Drug: Cyclophosphamide
  • Drug: Rituximab
Strati P, Keating MJ, O'Brien SM, Burger J, Ferrajoli A, Jain N, Tambaro FP, Estrov Z, Jorgensen J, Challagundla P, Faderl SH, Wierda WG. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood. 2014 Jun 12;123(24):3727-32. doi: 10.1182/blood-2013-11-538116. Epub 2014 Apr 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
August 2016
August 2016   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients will have a diagnosis of CLL, SLL, or CD20 positive low-grade lymphoproliferative disorder.
  • All patients with untreated Rai stage III-IV are eligible for this protocol. Prior treatment with single-agent rituximab permitted. OR Patients with untreated Rai stage 0-II who meet one or more criteria for active disease as defined by the International Working Group for CLL (IWCLL). Prior treatment with single-agent rituximab permitted.
  • Patients must have an ECOG performance status of 0-3.
  • Patients must have adequate renal and hepatic function (creatinine <2mg%, bilirubin <2mg%). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the study chairman.
  • Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply.
  • Patients must be 16 years of age or older.
  • Patients must sign informed consent indicating that they are aware of the investigational nature of this study according to the policies of the MDACC IRB.

Exclusion Criteria:

- None

Both
16 Years and older
No
Contact: William Wierda, M.D. 713/745-0428 wwierda@mdanderson.org
United States
 
NCT00759798
2008-0431, NCI-2012-01663
No
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: William Wierda, M.D. M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
May 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP