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Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

Primary Purpose

Mantle Cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fludarabine
Mitoxantrone
Rituximab
Zevalin
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring Fludarabine, Mitoxantrone, Rituximab, Zevalin, Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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: Absent cardiac blood pool on day 1, with high liver / spleen uptake Lung uptake greater than blood pool on day 1 or greater than liver on day 2-3 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

Sites / Locations

  • Massachusetts General Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabine, Mitoxantrone, Rituximab, Zevalin

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To describe the progression-free survival
To determine the safety of FMR + Zevalin in these subjects
To determine the impact of Zevalin on minimal residual disease in subjects with relapsed mantle cell lymphoma

Full Information

First Posted
July 7, 2005
Last Updated
April 22, 2014
Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, Biogen
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1. Study Identification

Unique Protocol Identification Number
NCT00119730
Brief Title
Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma
Official Title
Abbreviated Fludarabine / Mitoxantrone / Rituximab Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
December 2006 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital, Biogen

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma
Keywords
Fludarabine, Mitoxantrone, Rituximab, Zevalin, Mantle Cell Lymphoma, Relapsed Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Fludarabine, Mitoxantrone, Rituximab, Zevalin
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Given on days 1-3 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Mitoxantrone
Other Intervention Name(s)
Mitozantrone
Intervention Description
Given on day 1 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, MabThera and Zytux
Intervention Description
Given on day 1 of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
Zevalin
Other Intervention Name(s)
Ibritumomab tiuxetan
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
To describe the progression-free survival
Title
To determine the safety of FMR + Zevalin in these subjects
Time Frame
2 years
Title
To determine the impact of Zevalin on minimal residual disease in subjects with relapsed mantle cell lymphoma
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: Absent cardiac blood pool on day 1, with high liver / spleen uptake Lung uptake greater than blood pool on day 1 or greater than liver on day 2-3 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jennifer R Brown, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

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