Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Stage II, III, or IV Follicular NHL

NCT ID: NCT00732498

Last Updated: 2019-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-05-15
• Study Completion Date: 2018-10-15

Brief 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.

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.

Conditions

Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ESHAP followed by Zevalin and Rituximab

Etoposide, Methylprednisolone, Cytarabine, Cisplatin (ESHAP) infusion X 2 Cycles followed by Rituximab and In-Zevalin or Y-Zevalin.

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.

Y-Zevalin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

In-Zevalin

5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Methylprednisolone sodium succinate; Solu-Medrol; Vespesid; Cytosine Arabinoside; CDDP; Ibritumomab; Rituxan; Zevalin, Yttrium-90-Ibritumomab Tiuxetan; Yttrium-90-Ibritumomab Tiuxetan, Zevalin

Eligibility Criteria

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

Exclusion Criteria

Patients with impaired bone marrow reserve, as indicated by one or more of the following:

• Platelet count < 100,000 cells/mm3
• Hypocellular bone marrow (cellularity < or = 10%)
• 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

Prior radioimmunotherapy

Presence of CNS lymphoma. Patients must not have clinical evidence of central nervous system (CNS) involvement by lymphoma.

Patients with abnormal liver function: total bilirubin > 2.0 mg/dL

Patients with abnormal renal function: serum creatinine > 2.0 mg/dL or creatinine clearance < 50 ml/min.

Patients who have received prior external beam radiation therapy to > 25% of active bone marrow (involved field or regional)

Patients who have received G-CSF or GM-CSF therapy within 2 weeks prior to treatment

Serious nonmalignant disease or infection which, in the opinion of the investigator and/or the sponsor, would compromise other protocol objectives

Major surgery, other than diagnostic surgery, within 4 weeks

Patients with pleural effusion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Arizona

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel O. Persky, MD

Role: PRINCIPAL_INVESTIGATOR

University of Arizona

Locations

The University of Arizona Cancer Center

Tucson, Arizona, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.ncbi.nlm.nih.gov/pubmed/29471300

Journal Article

Other Identifiers

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000597508

Identifier Type: OTHER

Identifier Source: secondary_id

0500000303

Identifier Type: OTHER

Identifier Source: secondary_id

05-0303-04

Identifier Type: -

Identifier Source: org_study_id