Overview

This trial is active, not recruiting.

Condition lymphoma
Treatments methylprednisolone, etoposide, cytarabine, cisplatin, rituximab, in-zevalin, y-zevalin
Phase phase 2
Target CD20
Sponsor University of Arizona
Collaborator National Cancer Institute (NCI)
Start date May 2006
End date December 2016
Trial size 52 participants
Trial identifier NCT00732498, 05-0303-04, 0500000303, CDR0000597508, P30CA023074

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Etoposide, Methylprednisolone, Cytarabine, Cisplatin (ESHAP) infusion X 2 Cycles followed by Rituximab and In-Zevalin or Y-Zevalin.
methylprednisolone Methylprednisolone sodium succinate
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.
etoposide Vespesid
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.
cytarabine Cytosine Arabinoside
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.
cisplatin CDDP
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.
rituximab Ibritumomab
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.
in-zevalin Zevalin, Yttrium-90-Ibritumomab Tiuxetan
5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.
y-zevalin Yttrium-90-Ibritumomab Tiuxetan, 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.

Primary Outcomes

Measure
Progression-free survival at 1 year
time frame: 1 year
Median time to progression
time frame: 5 years

Secondary Outcomes

Measure
Overall and complete response rates
time frame: 5 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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 - 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 - 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

Additional Information

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
Principal investigator Soham D Puvvada, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by University of Arizona.