Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Dana-Farber Cancer Institute.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Massachusetts General Hospital
Biogen Idec
Information provided by (Responsible Party):
Jennifer R. Brown, MD, PhD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00119730
First received: July 7, 2005
Last updated: February 20, 2013
Last verified: February 2012
  Purpose
  • 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.

Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Fludarabine
Drug: Mitoxantrone
Drug: Rituximab
Drug: Zevalin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Abbreviated Fludarabine / Mitoxantrone / Rituximab Chemotherapy Followed by Zevalin for Relapsed Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To describe the progression-free survival [ Time Frame: TBD ] [ Designated as safety issue: No ]
  • To determine the safety of FMR + Zevalin in these subjects [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  • To determine the impact of Zevalin on minimal residual disease in subjects with relapsed mantle cell lymphoma [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2005
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Intervention Details:
    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
    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.
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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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:

    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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00119730

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Dana-Farber Cancer Institute
Massachusetts General Hospital
Biogen Idec
Investigators
Principal Investigator: Jennifer R Brown, MD, PhD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Jennifer R. Brown, MD, PhD, Assistant Professor of Medicine, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00119730     History of Changes
Other Study ID Numbers: 04-251
Study First Received: July 7, 2005
Last Updated: February 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Dana-Farber Cancer Institute:
Fludarabine
Mitoxantrone
Rituximab
Zevalin
Mantle Cell Lymphoma
Relapsed Mantle Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Fludarabine
Fludarabine monophosphate
Rituximab
Mitoxantrone
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Immunosuppressive Agents
Immunologic Factors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antirheumatic Agents

ClinicalTrials.gov processed this record on April 22, 2014