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FCR Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00381004
Recruitment Status : Completed
First Posted : September 27, 2006
Results First Posted : August 14, 2015
Last Update Posted : January 14, 2016
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if using a combination of fludarabine, cyclophosphamide, and rituximab, with sargramostim (GM-CSF) can help to control previously untreated chronic lymphocytic leukemia (CLL). The safety of this combination will also be studied. This study will evaluate antibody-dependent cellular cytotoxicity (ADCC) and its relationship to response.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Cyclophosphamide Drug: Fludarabine Drug: Sargramostim Drug: Rituximab Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Fludarabine, Cyclophosphamide, and Rituximab (FCR) Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia
Study Start Date : September 2006
Actual Primary Completion Date : December 2014
Actual Study Completion Date : December 2014


Arm Intervention/treatment
Experimental: FCR + Sargramostim
Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m^2 IV Days 2-4; Course 2-6: 25 mg/m^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m^2 Days 1-3. Rituximab - Course 1: 375 mg/m^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m^2 SQ Days -1 and 4-10.
Drug: Cyclophosphamide
Course 1: 250 mg/m^2 by vein over 5-30 minutes on Days 2, 3, and 4; Course 2 - 6: 250 mg/m^2 by vein over 5-30 minutes on Days 1 - 3
Other Names:
  • cytoxan
  • neosar

Drug: Fludarabine
Course 1: 25 mg/m^2 by vein over 5-30 minutes on Days 2,3, and 4; Course 2 - 6: 25 mg/m^2 by vein over 5-30 minutes on Days 1 - 3
Other Names:
  • Fludarabine monophosphate
  • Fludara

Drug: Sargramostim
Course 1: 250 mcg/m^2 subcutaneous (SQ) on Days -1 and Days 5 - 11; Course 2 - 6: 250 mcg/m^2 SQ on Days -1 and Days 4 - 10
Other Names:
  • GM-CSF
  • Leukine

Drug: Rituximab
Course 1: 375 mg/m^2 by vein over 2-6 Hours on Day 1; Course 2 - 6: 500 mg/m^2 by vein over 2-6 Hours on Day 1
Other Name: Rituxan




Primary Outcome Measures :
  1. Participant Overall Response Rate (ORR) at 6 Months Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions. [ Time Frame: Baseline to 6 Months ]
    Complete Remission:Normal exam/No symptoms; Absolute lymphocyte count (ALC)</=4x10^9/L, Hb>11 g/dL, absolute neutrophil count (ANC)>/=1.5x109/L, & platelet count>100x109/L. Bone marrow:<30% lymphocytes aspirate no biopsy evidence disease; Disappearance palpable lymph nodes/spleen/liver, no new lesions. Partial Remission:ALC reduced 50%,either Hb>11 g/dL or 50% improvement (imp.) in deviation, or ANC>/=1.5x109/L or 50% imp., or platelet>100x109/L or 50% imp. in deviation from normal. Reduced 50% palpable lymph nodes/spleen/liver no new lesions. Nodular Partial Response:ALC</=4x109/L + Hb>11 g/dL, ANC>/=1.5x109/L & platelet count>100x109/L; <30% lymphocytes - bone marrow biopsy aspirate + lymphoid nodules;No palpable lymph nodes/spleen/liver tumors without new lesions. Progressive Disease:50% increase (incr.) ALC>10x109/L twice; tumor lesion incr. 50% over entry or responder size at time max regression &/or appearance new malignant disease; Reappearance bone marrow disease.

  2. Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions. [ Time Frame: Baseline to 6 Months ]
    Complete Remission:Normal exam/No symptoms; Absolute lymphocyte count (ALC)</=4x10^9/L, Hb>11 g/dL, absolute neutrophil count (ANC)>/=1.5x109/L, & platelet count>100x109/L. Bone marrow:<30% lymphocytes aspirate no biopsy evidence disease; Disappearance palpable lymph nodes/spleen/liver, no new lesions. Partial Remission:ALC reduced 50%,either Hb>11 g/dL or 50% improvement (imp.) in deviation, or ANC>/=1.5x109/L or 50% imp., or platelet>100x109/L or 50% imp. in deviation from normal. Reduced 50% palpable lymph nodes/spleen/liver no new lesions. Nodular Partial Response:ALC</=4x109/L + Hb>11 g/dL, ANC>/=1.5x109/L & platelet count>100x109/L; <30% lymphocytes - bone marrow biopsy aspirate + lymphoid nodules;No palpable lymph nodes/spleen/liver tumors without new lesions. Progressive Disease:50% increase (incr.) ALC>10x109/L twice; tumor lesion incr. 50% over entry or responder size at time max regression &/or appearance new malignant disease; Reappearance bone marrow disease.


Secondary Outcome Measures :
  1. Number of Participants Progression-free [ Time Frame: 6 months or until disease progression if earlier ]
    Participants progression free as measured at six months following start of treatment. Criteria for Progressive Disease (PD): Peripheral blood: 50% increase in ALC with a level > 10 x 109/L on at least 2 occasions 2 weeks apart. Tumor: An increase of a lesion by 50% over the size present at entry on study or for patients who respond, the size at the time of maximum regression and/or the appearance of new areas of malignant disease. Reappearance of bone marrow disease. A deterioration in performance status or increasing symptoms do not constitute disease progression.



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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Untreated CLL, CLL/PLL, or SLL (small lymphocytic lymphoma) with indication for therapy. Indications for therapy include at least one of the following: (1) one or more disease-related symptoms [fever, night sweats, weight loss > 10% in prior 6 months, pronounced fatigue]; (2) advanced stage disease (Rai stage >/= 3 or Binet stage C); (3) autoimmune anemia and/or thrombocytopenia that is unresponsive to other therapies; (4) massive or progressive hepatomegaly and/or splenomegaly and/or lymphadenopathy; (5) recurrent infections; (6) rapid lymphocyte doubling time of < 6 months.
  • Patients who have been treated with not more than one regimen of immunotherapy (e.g. rituximab, alemtuzumab, rituximab plus alemtuzumab) for a diagnosis of CLL, CLL/PLL, or SLL (small lymphocytic lymphoma).
  • Beta-2-microglobulin </= 4 mg/dL.
  • Adequate liver function (total bilirubin </= 2.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) </=4 x ULN) and renal function (serum creatinine </= 2.0 mg/dL and/or creatinine clearance < 30 mL/hour). Patients with renal or liver dysfunction due to suspected organ infiltration by lymphocytes may be eligible after discussion with the Principal Investigator, but upper limits for creatinine even under these circumstances must be creatinine < 3mg/dL and bilirubin < 6 mg/dL. Patients with Gilbert's syndrome may be entered on study with bilirubin levels </= 4 mg/dL.
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
  • Signed informed consent in keeping with the policies of the hospital.
  • Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients of childbearing potential (non-childbearing is defined as >/= 1 year after menses cease and/or surgically sterilized) need a negative serum or urine pregnancy test within 2 days of study enrollment..

Exclusion Criteria:

  • Active hepatitis B (at least one of the following markers positive: HBsAg, hepatitis B e antigen (HBeAg), immunoglobulin M (IgM) anti-HBc, hepatitis B virus (HBV) DNA).
  • Concurrent chemotherapy or immunotherapy.
  • Pregnant patients.
  • History of HIV
  • Symptomatic central nervous system (CNS) disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00381004


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Bayer
Investigators
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Principal Investigator: Alessandra Ferrajoli, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00381004     History of Changes
Other Study ID Numbers: 2006-0267
First Posted: September 27, 2006    Key Record Dates
Results First Posted: August 14, 2015
Last Update Posted: January 14, 2016
Last Verified: December 2015
Keywords provided by M.D. Anderson Cancer Center:
Chronic Lymphocytic Leukemia
Leukemia
Cyclophosphamide
Fludarabine
Sargramostim
Rituximab
GM-CSF
FCR
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-Cell
Sargramostim
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Vidarabine
Cyclophosphamide
Rituximab
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents