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

Phase 2
18 Years
Open (Enrolling)
Mantle Cell Lymphoma

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Trial Information

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

- 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.

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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Jennifer R Brown, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana-Farber Cancer Institute


United States: Institutional Review Board

Study ID:




Start Date:

February 2005

Completion Date:

December 2013

Related Keywords:

  • Mantle Cell Lymphoma
  • Fludarabine
  • Mitoxantrone
  • Rituximab
  • Zevalin
  • Mantle Cell Lymphoma
  • Relapsed Mantle Cell Lymphoma
  • Lymphoma
  • Lymphoma, Mantle-Cell



Dana-Farber Cancer Institute Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617