Combination Chemotherapy, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed Stage II, Stage III, or Stage IV Follicular Non-Hodgkin Lymphoma

This study is currently recruiting participants.
Verified February 2013 by University of Arizona
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT00732498
First received: August 9, 2008
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving combination chemotherapy together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase II trial is studying giving combination chemotherapy followed by rituximab and yttrium Y 90 ibritumomab tiuxetan to see how well it works in treating patients with relapsed stage II, stage III, or stage IV follicular non-Hodgkin lymphoma.


Condition Intervention Phase
Lymphoma
Drug: methylprednisolone
Drug: Etoposide
Drug: Cytarabine
Drug: Cisplatin
Drug: Rituximab
Drug: In Zevalin
Drug: Y Zevalin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: PHASE II TRIAL OF YTTRIUM-90-IBRITUMOMAB TIUXETAN (ZEVALIN) RADIOIMMUNOTHERAPY AFTER CYTOREDUCTION WITH ESHAP CHEMOTHERAPY IN PATIENTS WITH RELAPSED FOLLICULAR NON-HODGKIN'S LYMPHOMA

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Progression-free survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To evaluate the 1-year progression-free survival (PFS) of patients with relapsed follicular non-Hodgkin's lymphoma (NHL) treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy.

  • Median time to progression [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To evaluate the median TTP of patients with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy.


Secondary Outcome Measures:
  • Overall and complete response rates [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To evaluate the overall (ORR) and complete response rates (CR) of patients with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy


Estimated Enrollment: 52
Study Start Date: May 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ESHAP followed by Zevalin
ESHAP infusion X 2 Cycles followed by Zevalin infusion.
Drug: methylprednisolone
250 mg/m2/day IV over 1 hour days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.
Drug: Etoposide
40 mg/day IV over 1 hour days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.
Drug: Cytarabine
2000 mg/m2 IV over 2 hours days 4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.
Drug: Cisplatin
25 mg/m2/day IV at 1mg/min days 1,2,3,4 every 28 days for 2 cycles. If bone marrow <25% involved and expected biodistribution after 2 cycles yttrium-90-ibritumomab tiuxetan (Zevalin) to be administered.
Drug: Rituximab
250 mg/m2 slow IV over days 1, then 7,8 or 9 prior to In Zevalin. Rituximab + Zevalin regimen is given 4-6 weeks after completion of 2 cycles of ESHAP. Treatment can be completed within 7-9 days in an outpatient setting.
Drug: In Zevalin
5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.
Other Name: Zevalin, Yttrium-90-Ibritumomab Tiuxetan
Drug: Y Zevalin
Platelet counts from 100,000/mm3 to 149,000/mm3 will receive 0.3 mCi/kg. Platelet counts from >/= 150,000/mm3 will receive 0.4 mCi/kg, not to exceed 32 mCi Y Zevalin. Slow IV push over 10 minutes, days 7,8 or 9 given within 4 hours after Rituximab.
Other Name: Yttrium-90-Ibritumomab Tiuxetan, Zevalin

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the 1-year progression-free survival of patients with relapsed stage II-IV follicular non-Hodgkin lymphoma treated with ESHAP chemotherapy for cytoreduction followed by yttrium Y 90 ibritumomab tiuxetan radioimmunotherapy.
  • To evaluate the median time to progression in these patients.

Secondary

  • To evaluate the overall and complete response rates in patients treated with this regimen.

OUTLINE:

  • ESHAP chemotherapy: Patients receive ESHAP chemotherapy comprising etoposide IV over 1 hour, methylprednisolone IV, cisplatin IV on days 1-4, and cytarabine IV over 2 hours on day 1. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity.
  • Radioimmunotherapy: Between 4-6 weeks after completion of ESHAP chemotherapy, patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 1. Patients with < 25% bone marrow involvement and expected biodistribution proceed to treatment. Patients receive rituximab IV followed by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 7, 8, or 9.

After completion of study treatment, patients are followed periodically.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of follicular non-Hodgkin lymphoma (NHL)

    • Bulky stage II, stage III, or stage IV disease

      • Bulky disease is defined as any tumor measuring 10.0 cm or more or occupying ≥ one-third of the chest diameter
  • In first, second, third, or fourth relapse after chemotherapy

    • Unilateral or bilateral bone marrow aspirate and biopsy with cytogenetics within the past 42 days
  • Tumor CD20 positive by either flow cytometry or immunoperoxidase staining of paraffin sections using anti-CD20 antibodies
  • Bidimensionally measurable disease

    • Patients with non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within the past 42 days
  • No presence of CNS lymphoma
  • No chronic lymphocytic leukemia
  • No HIV- or AIDS-related lymphoma
  • No presence of pleural effusion

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-2
  • ANC ≥ 1,500/μL (unless decreased counts are due to marrow involvement with NHL)
  • Platelet count > 100,000/μL (unless decreased counts are due to marrow involvement with NHL)
  • Serum creatinine ≤ 2.0 mg/dL
  • Creatinine clearance ≤ 50 mL/min
  • Serum bilirubin ≤ 2.0 mg/dL
  • No renal insufficiency or renal failure
  • No known HIV positivity
  • Not pregnant or nursing
  • No prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer with 5-year disease-free status
  • No impaired bone marrow reserve, including any of the following:

    • Hypocellular bone marrow (cellularity ≤ 15%)
    • Marked ( ≥ 10%) reduction in bone marrow precursors of one or more cell lines (granulocytic, megakaryocytic, erythroid) (beyond that which would be expected for the patient's age and bone marrow cellularity)
    • History of failed stem cell collection
  • No serious, non-malignant disease or infection which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives

PRIOR CONCURRENT THERAPY:

  • At least 3 weeks since all prior therapy (6 weeks for rituximab) and recovered
  • No prior myeloablative therapies with autologous bone marrow transplantation or peripheral blood stem cell rescue
  • No prior radioimmunotherapy
  • No prior external beam radiotherapy to > 25% of active bone marrow (involved field or regional)
  • More than 4 weeks since prior major surgery, other than diagnostic surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00732498

Locations
United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724
Contact: Thomas P. Miller, MD    866-278-1554      
Contact: Ruth Cañamar    520-626-6515      
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Thomas P. Miller, MD University of Arizona
  More Information

Additional Information:
No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT00732498     History of Changes
Other Study ID Numbers: 05-0303-04, P30CA023074, CDR0000597508, HSC#0567, UARIZ-SRC17899
Study First Received: August 9, 2008
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Arizona:
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Cisplatin
Cytarabine
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Antibodies, Monoclonal
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents

ClinicalTrials.gov processed this record on April 21, 2014