FCM-R (Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab) in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) < 70 Years

NCT00254410 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2005-0106NCI-2010-00437
• Study Type: interventional
• Target: 30
• 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 mitoxantrone plus rituximab, with the growth factor pegylated filgrastim, will improve the response to treatment, and increase the time this response lasts, for patients with previously untreated CLL. The safety of this combination will also be studied.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Untreated; Fludarabine; Fludara; Cyclophosphamide; Cytoxan; Mitoxantrone; Novantrone; Rituximab; Rituxan; Pegylated Filgrastim; Neupogen

Outcome Measures

Primary Outcomes (2)

• Clinical Response Rate at 3 Months

  Clinical Response Rate (combined morphological \[NCI Working Group (WG) criteria\] + flow cytometry criteria) at 3 months following treatment. Courses will be repeated every 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and toxicities for a maximum of 6 courses. Patients will be evaluated for response after 3 and 6 courses. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of chemotherapy.

  End of cycle 3

• Clinical Response Rate at 6 Months

  Clinical Response Rate (combined morphological \[NCI WG criteria\] + flow cytometry criteria) at 6 months following treatment. Courses will be repeated every 28 to 42 days (+/- 7 days) depending on recovery of peripheral blood counts and toxicities for a maximum of 6 courses. Patients will be evaluated for response after 3 and 6 courses. Bone marrow biopsies will be performed at the end of Cycles 3 and 6 of chemotherapy.

  End of Cycle 6

Secondary Outcomes (2)

• Molecular Response Rate at 3 Months

  End of cycle 3

• Molecular Response Rate at 6 Months

  End of 6 months

Study Arms (1)

FCM-R + Pegylated Filgrastim

EXPERIMENTAL

Fludarabine 25 mg/m2 on Days 2,3,4 i.v. 5-30 mins for course 1, and on Days 1 - 3 for courses 2 - 6. Cyclophosphamide 250 mg/m2 on Day 2,3,4 i.v. 5-30 mins for course 1, and on Days1 - 3 for courses 2 - 6. Mitoxantrone 6 mg/m2 on Day 2 i.v. 30-60 mins for course 1, and on Day 1 for courses 2 - 6. Rituximab 375 mg/m2 on Day 1 i.v. 2-6 hours for course 1 and 500 mg/m2 on Day 1 for courses 2 - 6. Pegylated Filgrastim - 6 mg on Day 4,s.c. for course 1 and on Day 3 for courses 2 - 6.

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Mitoxantrone; Drug: Rituximab; Drug: Filgrastim

Interventions

Fludarabine DRUG

Fludarabine 25 mg/m2 on Days 2,3,4 i.v. 5-30 mins for course 1, and on Days 1 - 3 for courses 2 - 6

Also known as: Fludara®

FCM-R + Pegylated Filgrastim

Cyclophosphamide DRUG

Cyclophosphamide 250 mg/m2 on Day 2,3,4 i.v. 5-30 mins for course 1, and on Days1 - 3 for courses 2 - 6.

Also known as: Cytoxan®

FCM-R + Pegylated Filgrastim

Mitoxantrone DRUG

Mitoxantrone 6 mg/m2 on Day 2 i.v. 30-60 mins for course 1, and on Day 1 for courses 2 - 6.

Also known as: Novantrone®

FCM-R + Pegylated Filgrastim

Rituximab DRUG

Rituximab 375 mg/m2 on Day 1 i.v. 2-6 hours for course 1 and 500 mg/m2 on Day 1 for courses 2 - 6.

Also known as: Rituxan®

FCM-R + Pegylated Filgrastim

Filgrastim DRUG

Pegylated Filgrastim - 6 mg on Day 4,s.c. for course 1 and on Day 3 for courses 2 - 6.

Also known as: Neupogen®

FCM-R + Pegylated Filgrastim

Eligibility Criteria

• Age: Up to 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Untreated CLL, CLL/ prolymphocytic leukemia (PLL), or small lymphocytic lymphoma (SLL) with indication for therapy (Indications for therapy include at least one of the following: i) one or more disease-related symptoms \[fever, night sweats, weight loss, pronounced fatigue\]; ii) advanced stage disease (Rai stage \>/= 3 or Binet stage C); iii) autoimmune anemia and/or thrombocytopenia that is unresponsive to other therapies; iv) massive or progressive hepatomegaly and/or splenomegaly and/or lymphadenopathy; iv) recurrent infections; v) rapid lymphocyte doubling time of \< 6 months).
• Age \< 70 years.
• 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). 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.
• Beta-2-microglobulin \</= 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 postmenopausal or surgically sterilized) need a negative serum or urine pregnancy test within 14 days of study enrollment.

You may not qualify if:

• Active hepatitis B (at least one of the following markers positive: HBsAg, HBeAg, Immunoglobulin M (IgM) hepatitis B core antibody (anti-HBc), Hepatitis B (HBV) DNA).
• Concurrent chemotherapy or immunotherapy.
• Pregnant patients.
• History of HIV
• Symptomatic central nervous system (CNS) disease
• Symptomatic heart disease (NYHA class \>/= 3) or left ventricle (LV) ejection fraction \< 40% (by multiple gated acquisition scan (MUGA) or echocardiogram)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• OSI Pharmaceuticals: collaborator
• Genentech, Inc.: 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

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Mitoxantrone; Rituximab; Filgrastim

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; 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; Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Quinones; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Results Point of Contact

• Title: Wierda,William G, MD./Professor
• Organization: The University of Texas MD Anderson Cancer Center

wwierda@mdanderson.org

713-745-0428

Study Officials

• William G. Wierda, MD, PHD, BS

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: November 14, 2005
• First Posted: November 16, 2005
• Study Start: March 14, 2005
• Primary Completion: September 14, 2017
• Study Completion: September 14, 2017
• Last Updated: May 1, 2019
• Results First Posted: December 6, 2018

Record last verified: 2019-04

Locations

US (1)