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

NCT00732498 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 05-0303-04P30CA023074CDR00005975080500000303
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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.

  1 year

• 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.

  5 years

Secondary Outcomes (2)

• Overall Response Rate

  5 years

• Complete Response Rate

  5 years

Study Arms (1)

ESHAP followed by Zevalin and Rituximab

EXPERIMENTAL

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

Drug: Methylprednisolone; Drug: Etoposide; Drug: Cytarabine; Drug: Cisplatin; Drug: Rituximab; Drug: In-Zevalin; Drug: Y-Zevalin

Interventions

Methylprednisolone 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.

Also known as: Methylprednisolone sodium succinate, Solu-Medrol

ESHAP followed by Zevalin and Rituximab

Etoposide 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.

Also known as: Vespesid

ESHAP followed by Zevalin and Rituximab

Cytarabine 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.

Also known as: Cytosine Arabinoside

ESHAP followed by Zevalin and Rituximab

Cisplatin 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.

Also known as: CDDP

ESHAP followed by Zevalin and Rituximab

Rituximab 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.

Also known as: Ibritumomab, Rituxan

ESHAP followed by Zevalin and Rituximab

In-Zevalin DRUG

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

Also known as: Zevalin, Yttrium-90-Ibritumomab Tiuxetan

ESHAP followed by Zevalin and Rituximab

Y-Zevalin 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.

Also known as: Yttrium-90-Ibritumomab Tiuxetan, Zevalin

ESHAP followed by Zevalin and Rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

Related Links

• Journal Article

MeSH Terms

Conditions

Lymphoma; Lymphoma, Follicular

Interventions

Methylprednisolone; Methylprednisolone Hemisuccinate; Etoposide; Cytarabine; Cisplatin; Rituximab; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: NCTN Program Coordinator
• Organization: University of Arizona

aselegue@email.arizona.edu

520-626-0301

Study Officials

• Daniel O. Persky, MD

  University of Arizona

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2008
• First Posted: August 12, 2008
• Study Start: May 15, 2006
• Primary Completion: October 15, 2018
• Study Completion: October 15, 2018
• Last Updated: September 4, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Locations

US (1)