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

NCT00290511 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: ID03-0287NCI-2011-02453
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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

Conditions

Lymphoma

Keywords

Follicular Lymphoma; Zevalin; Ibritumomab Tiuxetan; IDEC-Y2B8; Fludarabine; Fludara; Dexamethasone; Mitoxantrone; Rituximab; Rituxan; R-FND; Fludarabine Phosphate; Decadron

Outcome Measures

Primary Outcomes (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

  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)

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

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

• Tolerance and Efficacy of Maintenance Therapy With Rituximab

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

• Median Progression Free Survival

  up to 5 years

• Progression Free Survival at 10 Years

  10 years

• Overall Survival

  up to 5 years

Study Arms (1)

R-FIND + Zevalin

EXPERIMENTAL

Fludarabine 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.

Drug: Fludarabine; Drug: Mitoxantrone; Drug: Rituximab; Drug: Zevalin; Drug: Dexamethasone

Interventions

Fludarabine DRUG

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

Also known as: Fludarabine Phosphate, Fludara

R-FIND + Zevalin

Mitoxantrone DRUG

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

Also known as: Novantrone

R-FIND + Zevalin

Rituximab DRUG

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).

Also known as: Rituxan

R-FIND + Zevalin

Zevalin DRUG

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

Also known as: Ibritumomab Tiuxetan, IDEC-Y2B8

R-FIND + Zevalin

Dexamethasone DRUG

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

Also known as: Decadron

R-FIND + Zevalin

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

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

Lymphoma; Lymphoma, Follicular

Interventions

fludarabine; fludarabine phosphate; Mitoxantrone; Rituximab; ibritumomab tiuxetan; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Anthraquinones; Anthrones; Anthracenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Quinones; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Dr. Felipe Samaniego, MD-Professor, Lymphoma-Myeloma
• Organization: UT MD Anderson Cancer Center

fsamaniego@mdanderson.org

(713) 745-6824

Study Officials

• Nathan Fowler, 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: February 10, 2006
• First Posted: February 13, 2006
• Study Start: June 29, 2004
• Primary Completion: February 12, 2021
• Study Completion: February 12, 2021
• Last Updated: April 22, 2022
• Results First Posted: April 22, 2022

Record last verified: 2022-03

Locations

US (1)