Rituximab, Fludarabine, Mitoxantrone, Dexamethasone (R-FND) Plus Zevalin for High-Risk Follicular Lymphoma - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Genentech Biogen Idec
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00290511

Purpose

Primary Objectives:

To assess whether the time to progression for these high-risk patients can be prolonged to a median of 36 months, compared to the historical expectation of approximately 24 months.
To assess the tolerance and efficacy of Y2B8 (Zevalin) after R-FND (rituximab, fludarabine, mitoxantrone, dexamethasone) in patients with high-risk stage III-IV follicular lymphoma.
To assess overall response, failure-free survival, and survival of this strategy compared to our historical experience with FND (fludarabine, mitoxantrone, dexamethasone) alone or R-FND.
To assess the tolerance and efficacy of maintenance therapy with rituximab.
To maximize the 12-month molecular remission rate for patients with high-risk stage III-IV follicular lymphoma.
To correlate the results of quantitative PCR assay with classical PCR and with clinical outcome.

Condition	Intervention	Phase
Lymphoma	Drug: Fludarabine Drug: Mitoxantrone Drug: Rituximab Drug: Zevalin Drug: Dexamethasone	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Dexamethasone Dexamethasone acetate Dexamethasone Sodium Phosphate Doxiproct plus Mitoxantrone hydrochloride Mitoxantrone Fludarabine Fludarabine monophosphate Rituximab Ibritumomab tiuxetan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study of R-FND, Followed by Zevalin Radioimmunotherapy, and Subsequent Maintenance Rituximab for Advanced Stage Follicular Lymphoma With High-Risk Features

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

To learn if chemotherapy given with rituximab, followed by Ibritumomab tiuxetan (Zevalin), and then followed by rituximab can help to control lymphoma. [ Time Frame: 5 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	50
Study Start Date:	June 2004
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental R-FIND + Zevalin	Drug: Fludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Drug: Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. Drug: Rituximab 375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total). Drug: Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Drug: Dexamethasone 20 mg PO or IV daily on Days 2-6.

Arms

Assigned Interventions

1: Experimental

R-FIND + Zevalin

Drug: Fludarabine

25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4.

Drug: Mitoxantrone

10 mg/m^2 IV over 5-30 minutes on Day 2.

Drug: Rituximab

375 mg/m^2 IV over 4-6 hours on Day 1 and 8; maintenance Rituximab = 375 mg/m^2 IV over 4-6 hours on Day 1 only, a single dose every other month for 12 months (6 doses total).

Drug: Zevalin

0.3 mCi/kg IV after 4 cycles of R-FND.

Drug: Dexamethasone

20 mg PO or IV daily on Days 2-6.

Detailed Description:

The treatments used in this program include several standard chemotherapy agents (fludarabine, mitoxantrone, and dexamethasone). Also, immune therapy agents will be given, including rituximab (a monoclonal antibody that attacks B-cells, which is what this type of lymphoma is made of), and Ibritumomab tiuxetan (another similar monoclonal antibody, which delivers radiation to the lymphoma cells to strengthen the attack).

Before treatment starts, you will have a complete physical exam, including blood (about 4 tablespoons) and urine tests. Chest x-rays and CT scans will be done. Bone marrow samples will be taken. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Tests of heart function and lung function will be done, including x-rays and either a scan or ultrasound of the heart. Tumors and lesions will be measured by physical exam and by x-rays. Women who are able to have children must have a negative blood pregnancy test.

You will receive rituximab on Days 1 and 8 of the first cycle, and on Day 1 only of Cycles 2-4 of the monthly cycles of chemotherapy, called R-FND. R-FND includes rituximab and fludarabine, mitoxantrone, and dexamethasone. Fludarabine will be given for 3 days, mitoxantrone for 1 day, and dexamethasone for 5 days of each 28-day cycle (FND). After 4 cycles of R-FND, you will receive Ibritumomab tiuxetan. After the Ibritumomab tiuxetan, you will receive rituximab every 2 months for 1 year. All are given by vein. Sometimes dexamethasone can be given in pill form.

During the study, you will have blood tests (about 2 tablespoons), sometimes every week. Every 2 cycles, you will have a chest x-ray and CT scans of the abdomen and pelvis. Bone marrow samples will be taken. Heart function tests will be done as needed.

If you desire, it may be possible for you to receive some of your study treatment at home (from your home doctor). Your study doctor will discuss this possibility with you. If this is the case, your home doctor will receive a letter telling him about this study and asking him if he wishes to participate in your treatments. He will be asked to provide the study doctors at M. D. Anderson specific information about your treatments and any side effects you may have. All communications between your home doctor and your study doctors will be included as part of your M. D. Anderson medical record.

After the study ends, you will return for checkups every 3 months in the first year, every 4 months in Years 2 and 3, and every 6 months in Years 4 and 5. After that, checkups will be needed once a year. Blood (about 2 tablespoons) and bone marrow samples will be taken at these visits.

This is an investigational study. About 50 patients will take part in the study. All will be enrolled at M. D. Anderson.

Eligibility

Ages Eligible for Study:	60 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with high-risk Ann Arbor stage III-IV follicular lymphoma. High-risk is defined by advanced stage (III or IV), plus any 2 of the following features:
- Age 60 or greater;
- Elevated LDH;
- Hgb < 12; OR
- Number of involved nodal sites 5 or more
Patients will be previously untreated.
Adequate organ function.
Follicular lymphoma, grade 3 (follicular large cell lymphoma): If eligible for a current large cell lymphoma protocol, that alternative protocol is recommended, particularly grade 3b or FLCL patients characterized as large non-cleaved cell. However, both FND and rituximab have established efficacy in FLCL, so if a patient is not eligible for a protocol for aggressive lymphoma (e.g., because of SCCL in the marrow), then registration on this trial is permitted.
Biopsy or FNA material is strongly recommended for bcl-2 studies to verify rearrangement status of all patients who are designated "germline" (see section 6.4). For other patients, tissue availability is desirable but not mandatory.
Patients must have a performance status of Zubrod 3 or better.
Patients must have adequate renal and hepatic function (creatinine < 2 mg%; bilirubin < 2 mg%). Patients with renal or liver dysfunction due to organ infiltration by lymphoma may be eligible after discussion with the study chairman.
Patients may not receive other concurrent chemotherapy, radiotherapy, or immunotherapy.
Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.

Exclusion Criteria:

Patients who are unable or unlikely to be able to adhere to the treatment plan or to return to Houston for follow-up visits because of geographical, economic, emotional, or social considerations are not eligible for this study. Note: some follow-up care may be provided by outside physicians as long as the MDACC protocol for outside physician participation is strictly adhered to.
Patients with an absolute peripheral granulocyte count of < 1,000 and platelet count < 100,000 unless due to marrow infiltration or hypersplenism.
Patients with organ dysfunction, including bilirubin of > 2 mg% or serum creatinine level > 2 mg%, unless the alteration is due to lymphoma.
Patients with HIV infection should not be registered on this protocol.
Patients with an antecedent malignancy whose prognosis is poor (< 90% probability of surviving for 5 yrs).
All patients should have a cardiac ejection fraction of 50% or more by echocardiography or MUGA.
Patients who will not accept transfusions of blood products or supportive care measures such as antibiotics are not eligible for this study.
Female patients must not be pregnant or lactating, and men and women of reproductive potential must follow accepted birth control methods.
Patients who have received prior murine antibody therapy will be excluded.
Patients with evidence of active or prior infection of Hepatitis B are excluded. (Note: Persons vaccinated for Hepatitis B who have + antibodies are not excluded).

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00290511

Contacts

Contact: Peter McLaughlin, MD

713-792-2860

Locations

United States, Texas
U.T.M.D. Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Peter McLaughlin, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

Genentech

Biogen Idec

Investigators

Principal Investigator:

Peter McLaughlin, MD

U.T.M.D. Anderson Cancer Center

More Information

UT MD Anderson Cancer Center This link exits the ClinicalTrials.gov site

Responsible Party:	U.T.M.D. Anderson Cancer Center ( Peter McLaughlin, MD/Professor )
Study ID Numbers:	ID03-0287
Study First Received:	February 10, 2006
Last Updated:	December 6, 2008
ClinicalTrials.gov Identifier:	NCT00290511
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Follicular Lymphoma
Zevalin
Ibritumomab Tiuxetan
IDEC-Y2B8
Fludarabine
Dexamethasone

Mitoxantrone
Rituximab
Rituxan
R-FND
Fludarabine Phosphate
Decadron

Study placed in the following topic categories:

Dexamethasone
Immunoproliferative Disorders
Rituximab
Lymphoma, Follicular
Fludarabine monophosphate
Lymphatic Diseases
Fludarabine

Mitoxantrone
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma
Follicular lymphoma
Dexamethasone acetate

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Sensory System Agents
Therapeutic Uses
Analgesics

Neoplasms by Histologic Type
Immune System Diseases
Antineoplastic Agents, Hormonal
Gastrointestinal Agents
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Autonomic Agents
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009