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LymphomaPhase 2NCT00290511

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

A Phase 2 study testing Fludarabine, Mitoxantrone and Rituximab in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The goal of this clinical research study is to learn if chemotherapy given with rituximab, followed by Ibritumomab tiuxetan (Zevalin), and then followed by rituximab can help to control lymphoma. The safety of this treatment schedule will also be studied. Objectives: 1. Read more about this study

Who is it for?
Ages 60 years and older
Conditions the study is for
Lymphoma
What is being tested?
Fludarabine, Mitoxantrone and Rituximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
1 siteUnited States
Study dates
29 Jun 2004to 12 Feb 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 60 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 fine-needle aspiration (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
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  • Patients must have adequate renal and hepatic function (creatinine < 2mg%; 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.

Who cannot join

  • 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 MD Anderson Cancer Center (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 multiple gated acquisition scan (MUGA).
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  • 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).

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this 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

The goal of this clinical research study is to learn if chemotherapy given with rituximab, followed by Ibritumomab tiuxetan (Zevalin), and then followed by rituximab can help to control lymphoma. The safety of this treatment schedule will also be studied.

Objectives:

  1. 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.
  2. 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
  3. 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
  4. To assess the tolerance and efficacy of maintenance therapy with rituximab.
  5. To maximize the 12-month molecular remission rate for patients with high-risk stage III-IV follicular lymphoma
  6. to correlate the results of quantitative PCR assay with classical PCR and with clinical outcome
Read the 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).

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. Ibritumomab tiuxetan and rituximab are approved by the FDA for commercial use. The other drugs used in the study are also approved for commercial use by the FDA. About 50 patients will take part in the study. All will be enrolled at M. D. Anderson.

Conditions
Lymphoma
Being tested
Fludarabine, Mitoxantrone, Rituximab, Zevalin, Dexamethasone
Keywords
Follicular Lymphoma, Zevalin, Ibritumomab Tiuxetan, IDEC-Y2B8, Fludarabine, Fludara, Dexamethasone, Mitoxantrone, Rituximab, Rituxan, R-FND, Fludarabine Phosphate, Decadron
Medical subject headings
Lymphoma, Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FludarabineDrug

    Also called Fludarabine Phosphate, Fludara

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

  • MitoxantroneDrug

    Also called Novantrone

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

  • RituximabDrug

    Also called Rituxan

    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).

  • ZevalinDrug

    Also called Ibritumomab Tiuxetan, IDEC-Y2B8

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

  • DexamethasoneDrug

    Also called Decadron

    20 mg by mouth (PO) or IV daily on Days 2-6.

Study groups in NCT00290511
Study groupRoleWhat they receive
R-FIND + ZevalinExperimentalFludarabine 25 mg/m^2 intravenous (IV) over 5-30 minutes on Days 2-4. Mitoxantrone 10 mg/m^2 IV over 5-30 minutes on Day 2. 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). Zevalin 0.3 mCi/kg IV after 4 cycles of R-FND. Dexamethasone 20 mg by mouth (PO) or IV daily on Days 2-6.
Receives: Drug: Fludarabine; Drug: Mitoxantrone; Drug: Rituximab; Drug: Zevalin; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Time to Progression (TTP)

    Regimen regarded as a success if median TTP can be prolonged to 36 months or greater. Time to Progression measured by the method of Kaplan and Meier, and accompanied by 95% confidence interval. Complete Response (CR) defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays and Partial Response (PR) is defined as a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. av

    Measured: baseline, 2 and 4 courses, approximately month 8, 9, and 12 months, then restaging every 4 months, then at 2 years every 4-6 months, then yearly until progressive disease or lost to follow up, average of 10 years

Secondary outcomes (6)

  1. Tolerance and Efficacy of Maintenance Therapy With Yttrium-90 Ibritumomab Tiuxetan (YIT)

    To assess the tolerance and efficacy of maintenance therapy with YIT. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.

    Measured: cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years

  2. Tolerance and Efficacy of Maintenance Therapy With Rituximab

    To assess the tolerance and efficacy of maintenance therapy with rituximab. Participants proceeded to the rituximab maintenance program of 6 treatments comprising 1 every 2 months. CR: defined as those who achieve a normal state which includes no detectable evidence of disease on x-rays. CRu: defined as "CR unconfirmed" on the basis of minimal residual abnormalities on x-ray such as a residual mass <25% of original measurement, and or residual indeterminate bone marrow aggregates. PR: a 50% or more reduction in the sum of the products of the diameters of the 6 largest measurable lesions. No new sites of disease. Progressive disease (PD) is also defined by the appearance of new lymph nodes, of other new or worsening sites of disease, such as > 50% increase in the size of liver and/or spleen, or a > 50% increase in absolute number of circulating lymphocytes.

    Measured: cycle 1 and every 2 weeks thereafter until completion of therapy, an average of 10 years

  3. Median Progression Free Survival

    Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. Median Progression Free Survival estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    Measured: up to 5 years

  4. Progression Free Survival at 10 Years

    Progression-free survival time is defined as time from registration/randomization to the date of progression or death from any cause. PFS was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    Measured: 10 years

  5. Overall Survival

    OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Median Overall Survival was estimated by the method of Kaplan and Meier, and accompanied by 95% confidence interval.

    Measured: up to 5 years

  6. Percentage of Participants With Overall Survival Rate at 10 Years

    OS is defined as the interval from first dose of study treatment to the date of death, irrespective of the cause of death; subjects still alive will be censored at the date of the last contact. Overall Survival Rate estimated by the method of Kaplan and Meier.

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Feb 2006 (estimated)
  2. Study start29 Jun 2004
  3. Primary completion12 Feb 2021
  4. Study completion12 Feb 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00290511
Sponsor's protocol ID
ID03-0287
Other IDs
NCI-2011-02453
Status last verified
Mar 2022
First submitted
10 Feb 2006
Last updated
22 Apr 2022
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludarabine, Mitoxantrone and Rituximab in people with Lymphoma, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Apr 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Time to Progression (TTP) (time frame: baseline, 2 and 4 courses, approximately month 8, 9, and 12 months, then restaging every 4 months, then at 2 years every 4-6 months, then yearly until progressive disease or lost to follow up, average of 10 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00290511.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2022.

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