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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Methylprednisolone
Etoposide
Cytarabine
Cisplatin
Rituximab
In-Zevalin
Y-Zevalin
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • The University of Arizona Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ESHAP followed by Zevalin and Rituximab

Arm Description

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

Outcomes

Primary Outcome Measures

Progression-free Survival at 1 Year
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
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 Response Rate
To evaluate the overall (ORR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy. Descriptive and summary statistics for demographic and clinical variables obtained. The incidences of reported adverse events (AEs) tabulated. Kaplan-Meier survival analysis for PFS and OS performed on TPP. All the analyses were performed using Stata [12].
Complete Response Rate
To evaluate the complete (CR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy

Full Information

First Posted
August 9, 2008
Last Updated
August 23, 2019
Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00732498
Brief Title
Rituximab, Yttrium Y 90 Ibritumomab Tiuxetan in Patients W/Relapsed Stage II, III, or IV Follicular NHL
Acronym
ESHAP
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
May 15, 2006 (Actual)
Primary Completion Date
October 15, 2018 (Actual)
Study Completion Date
October 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Arizona
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ESHAP followed by Zevalin and Rituximab
Arm Type
Experimental
Arm Description
Etoposide, Methylprednisolone, Cytarabine, Cisplatin (ESHAP) infusion X 2 Cycles followed by Rituximab and In-Zevalin or Y-Zevalin.
Intervention Type
Drug
Intervention Name(s)
Methylprednisolone
Other Intervention Name(s)
Methylprednisolone sodium succinate, Solu-Medrol
Intervention Description
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
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Vespesid
Intervention Description
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
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Cytosine Arabinoside
Intervention Description
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
Intervention Name(s)
Cisplatin
Other Intervention Name(s)
CDDP
Intervention Description
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
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Ibritumomab, Rituxan
Intervention Description
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
Intervention Name(s)
In-Zevalin
Other Intervention Name(s)
Zevalin, Yttrium-90-Ibritumomab Tiuxetan
Intervention Description
5 mCi slow IV push over 10 minutes days 1. Given within 4 hours after Rituximab.
Intervention Type
Drug
Intervention Name(s)
Y-Zevalin
Other Intervention Name(s)
Yttrium-90-Ibritumomab Tiuxetan, Zevalin
Intervention Description
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 Outcome Measure Information:
Title
Progression-free Survival at 1 Year
Description
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.
Time Frame
1 year
Title
Median Time to Progression
Description
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.
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
To evaluate the overall (ORR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy. Descriptive and summary statistics for demographic and clinical variables obtained. The incidences of reported adverse events (AEs) tabulated. Kaplan-Meier survival analysis for PFS and OS performed on TPP. All the analyses were performed using Stata [12].
Time Frame
5 years
Title
Complete Response Rate
Description
To evaluate the complete (CR) response rate with relapsed follicular NHL treated with ESHAP chemotherapy for cytoreduction (2 cycles) followed by Ibritumomab tiuxetan (Zevalin) radioimmunotherapy
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel O. Persky, MD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Arizona Cancer Center
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/29471300
Description
Journal Article

Learn more about this trial

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

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