Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

April 22, 2014 updated by: Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute

Abbreviated Fludarabine / Mitoxantrone / Rituximab Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

  • The purpose of this study is to find out whether combining a short course of chemotherapy (Fludarabine, Mitoxantrone and Rituximab) followed by Zevalin will be effective in treating relapsed mantle cell lymphoma.
  • The secondary purposes of the study are to determine the safety and to evaluate whether there is additional benefit from Zevalin therapy following the chemotherapy.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • Patients receive fludarabine (days 1-3), mitoxantrone (day 1), and rituximab (day 1) of each 28-day cycle.
  • Patients undergo a CT scan and bone marrow biopsy after two cycles. Unless the cancer has progressed, the patient will then receive Zevalin study treatment.
  • Blood counts are taken every week for 12 weeks. After 12 weeks, a CT scan and bone marrow biopsy are performed.
  • Long-term followup is 4 years. Physical exam and blood work is performed every 3 months for the first two years. Following that, physical exams and blood work is every 6 months for another two years. CT scans and bone marrow biopsies are every 6 months during this 4 year followup period.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Histologically confirmed mantle cell lymphoma in 1st or 2nd relapse, or with persistent disease following induction therapy.
  • Measurable disease (lymph node > 1.5 cm)
  • No anti-cancer therapy for three weeks (six weeks if Rituximab, nitrosourea or Mitomycin C) prior to study initiation, and fully recovered from all toxicities associated with prior surgery, radiation treatments, chemotherapy, or immunotherapy
  • An IRB-approved signed informed consent
  • Age >/= 18 years
  • Expected survival >/= 3 months
  • ECOG performance status 0, 1, or 2
  • Acceptable hematologic status within two weeks prior to registration, including: * Absolute neutrophil count ([segmented neutrophils + bands] x total WBC) ≥ 1,500/mm3; * Platelet counts ≥ 100,000/mm3
  • Female patients who are not pregnant or lactating
  • Men and women of reproductive potential who are following accepted birth control methods (as determined by the treating physician, however abstinence is not an acceptable method)
  • Patients previously on Phase II drugs if no long-term toxicity is expected, and the patient has been off the drug for eight or more weeks with no significant post treatment toxicities observed

Inclusion Criteria for Proceeding with Zevalin:

  • Hematologic recovery from FMR (ANC >1500, platelets > 100,000)
  • Stable or responding disease on restaging following two cycles of FMR
  • < 25% of bone marrow cellularity involved with lymphoma on restaging bone marrow biopsy
  • Bone marrow cellularity at least 20% (including lymphoma and normal cells)
  • Total bilirubin < 2.0 mg/dL (if total bilirubin is >75% indirect, then may use direct bilirubin < 0.8 mg/dL)
  • Serum creatinine < 2.0 mg/dL
  • No G-CSF or GM-CSF therapy within two weeks prior to Zevalin treatment, or neulasta within four weeks prior to Zevalin treatment

  • No evidence of altered biodistribution of 111-In-Zevalin as indicated by:

    1. Absent cardiac blood pool on day 1, with high liver / spleen uptake
    2. Lung uptake greater than blood pool on day 1 or greater than liver on day 2-3
    3. Kidney (in posterior view) or bowel uptake greater than liver on day 2-3

Exclusion Criteria:

  • Patients with impaired bone marrow reserve, as indicated by one or more of the following: * Prior myeloablative therapies with allogeneic or autologous bone marrow transplantation (ABMT) or peripheral blood stem cell (PBSC) rescue; * Platelet count < 100,000 cells/mm3; * Prior external beam radiation to >25% of active bone marrow; * History of failed stem cell collection
  • Prior radioimmunotherapy
  • Known cardiac ejection fraction < 40%. In patients with prior adriamycin exposure >= 300 mg/m2, echocardiogram must be obtained within three months prior to registration
  • Known CNS lymphoma (lumbar puncture only required if symptomatic)
  • Chronic lymphocytic leukemia (CLL)
  • HIV or AIDS-related lymphoma
  • Pleural effusion or ascites
  • Abnormal liver function: total bilirubin > 2.0 mg/dL (if total bilirubin is >75% indirect, then may use direct bilirubin > 0.8 mg/dL)
  • Abnormal renal function: serum creatinine > 2.0 mg/dL
  • G-CSF or GM-CSF therapy within two weeks prior to treatment, or neulasta within four weeks
  • Positive direct antiglobulin test
  • Major surgery, other than diagnostic surgery, within four weeks
  • Serious nonmalignant disease or infection which in the opinion of the investigator would compromise protocol objectives

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fludarabine, Mitoxantrone, Rituximab, Zevalin
Drug: Fludarabine Given on days 1-3 of each 28-day cycle Drug: Mitoxantrone Given on day 1 of each 28-day cycle Drug: Rituximab Given on day 1 of each 28-day cycle Drug: Zevalin Given after two cycles if there is no disease progression.
Drug: Fludarabine
Given on days 1-3 of each 28-day cycle
Other Names:
  • Fludara
Drug: Mitoxantrone
Given on day 1 of each 28-day cycle
Other Names:
  • Mitozantrone
Drug: Rituximab
Given on day 1 of each 28-day cycle
Other Names:
  • Rituxan, MabThera and Zytux
Drug: Zevalin
After two cycles if there is no disease progression, zevalin treatment will be given. Rituximab will be given followed by an imaging dose of zevalin. Two or three scans will be performed over a week to determine if it is safe to give the full treatment dose of zevalin. The treatment dose is given with the second infusion or rituximab, seven days after the first dose.
Other Names:
  • Ibritumomab tiuxetan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary objective is to determine the response rate to two cycles of FMR + Zevalin in patients with relapsed mantle cell lymphoma, using a two-stage design.
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
To describe the progression-free survival
To determine the safety of FMR + Zevalin in these subjects
Time Frame: 2 years
2 years
To determine the impact of Zevalin on minimal residual disease in subjects with relapsed mantle cell lymphoma
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Dana-Farber Cancer Institute

Collaborators

Massachusetts General Hospital
Biogen

Investigators

  • Principal Investigator: Jennifer R Brown, MD, PhD, Dana-Farber Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2005

Primary Completion (Actual)

December 1, 2006

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

July 7, 2005

First Submitted That Met QC Criteria

July 7, 2005

First Posted (Estimate)

July 14, 2005

Study Record Updates

Last Update Posted (Estimate)

April 24, 2014

Last Update Submitted That Met QC Criteria

April 22, 2014

Last Verified

April 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 04-251

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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