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

NCT00381004 | Completed Phase 2 Results

• 1 other identifier: 2006-0267
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Leukemia; Cyclophosphamide; Fludarabine; Sargramostim; Rituximab; GM-CSF; FCR

Outcome Measures

Primary Outcomes (2)

• Participant Overall Response Rate (ORR) at 6 Months Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.

  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.

  Baseline to 6 Months

• Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.

  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.

  Baseline to 6 Months

Secondary Outcomes (1)

• Number of Participants Progression-free

  6 months or until disease progression if earlier

Study Arms (1)

FCR + Sargramostim

EXPERIMENTAL

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; Drug: Fludarabine; Drug: Sargramostim; Drug: Rituximab

Interventions

Cyclophosphamide DRUG

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

Also known as: cytoxan, neosar

FCR + Sargramostim

Fludarabine DRUG

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

Also known as: Fludarabine monophosphate, Fludara

FCR + Sargramostim

Sargramostim DRUG

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

Also known as: GM-CSF, Leukine

FCR + Sargramostim

Rituximab DRUG

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

Also known as: Rituxan

FCR + Sargramostim

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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..

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Bayer: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor; Rituximab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Alessandra Ferrajoli, MD/Professor, Leukemia
• Organization: The University of Texas (UT) MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

Study Officials

• Alessandra Ferrajoli, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 25, 2006
• First Posted: September 27, 2006
• Study Start: September 1, 2006
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 14, 2016
• Results First Posted: August 14, 2015

Record last verified: 2015-12

Locations

US (1)