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

NCT ID: NCT00637832

Last Updated: 2022-01-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-01
• Study Completion Date: 2015-01-06

Brief Summary

RATIONALE: 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. 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. 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 rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy and yttrium Y 90 ibritumomab tiuxetan works in treating patients with relapsed follicular non-Hodgkin lymphoma.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the response rates in patients with relapsed follicular non-Hodgkin lymphoma treated with short-duration rituximab and combination chemotherapy (R-chemo) followed by rituximab and yttrium Y 90 ibritumomab tiuxetan.

Secondary

• To evaluate the duration of response in patients treated with this regimen.
• To evaluate the quality of response in order to determine the conversion rate from partial response to complete response in patients treated with this regimen.
• To evaluate the toxicity of yttrium Y 90 ibritumomab tiuxetan when administered after 3 courses of R-chemo.

OUTLINE: This is a multicenter study.

• Chemoimmunotherapy (R-CHOP or R-CVP): Patients receive R-CHOP comprising rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Alternatively, patients who have already been exposed to prior tolerance doses of anthracyclines receive R-CVP comprising rituximab IV, cyclophosphamide IV, and vincristine IV on day 1 and oral prednisolone on days 1-5. Treatment repeats every 3 weeks for up to 3 courses.

Patients with objective evidence of response on CT scan or those with < 25% bone marrow involvement and no signs of bone marrow hypocellularity (< 15%) on bone marrow biopsy proceed to radioimmunotherapy.

• Radioimmunotherapy: Four to 6 weeks after completion of R-CHOP or R-CVP, patients receive rituximab IV followed no more than 4 hours later by yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes.

After completion of study therapy, patients are followed periodically for up to 5 years.

Conditions

Lymphoma

Study Design

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

Study Groups

single group

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisolone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

yttrium Y 90 ibritumomab tiuxetan

Intervention Type: RADIATION

Interventions

rituximab

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

prednisolone

Intervention Type: DRUG

vincristine sulfate

Intervention Type: DRUG

yttrium Y 90 ibritumomab tiuxetan

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed grade 1, 2, or 3 follicular non-Hodgkin lymphoma

• Stage II, III, or IV disease (according to the Ann Arbor staging system)
• CD20-positive disease
• Initial disease bulk ≤ 10 cm
• In first or second relapse after prior treatment with a rituximab-containing chemotherapy regimen (R-chemo) or chemotherapy alone

• Relapse must have occurred ≥ 6 months after completion of R-chemo

• Relapse that occurred < 6 months after completion of chemotherapy alone allowed
• Has at least one of the following symptoms requiring initiation of treatment:

• Nodal mass > 5 cm in its greater diameter
• B symptoms
• Elevated serum lactate dehydrogenase (LDH) or β2-microglobulin
• Involvement of ≥ 3 nodal sites (each with a diameter > 3 cm)
• Symptomatic splenic enlargement
• Compressive syndrome
• No primary refractory disease
• No large pleural or peritoneal effusions
• No CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy ≥ 6 months
• Absolute granulocyte count ≥ 1,500/mm³
• Platelet count ≥ 1,000/mm³
• Serum creatinine < 1.5 times upper limit of normal (ULN)
• Total bilirubin < 1.5 times ULN
• AST < 5 times ULN
• No active obstructive hydronephrosis
• No evidence of active infection requiring IV antibiotics
• No advanced heart disease or other serious illness that would preclude study evaluation
• No known HIV infection
• No human anti-mouse antibody (HAMA) reactivity
• No known hypersensitivity to murine antibodies or proteins
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 12 months after completion of study treatment
• No other prior malignancy, except for adequately treated skin cancer, cervical cancer in situ, or other cancer for which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior investigational drugs and recovered
• No prior radioimmunotherapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Southampton

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tim Illidge

Role: PRINCIPAL_INVESTIGATOR

The Christie NHS Foundation Trust

Locations

Christie Hospital

Manchester, England, United Kingdom

Mount Vernon Cancer Centre at Mount Vernon Hospital

Northwood, England, United Kingdom

Dorset Cancer Centre

Poole Dorset, England, United Kingdom

Southampton General Hospital

Southampton, England, United Kingdom

Saint Bartholomew's Hospital

London, , United Kingdom

Countries

United Kingdom

References

Illidge TM, McKenzie HS, Mayes S, Bates A, Davies AJ, Pettengell R, Stanton L, Cozens K, Hampson G, Dive C, Zivanovic M, Tipping J, Gallop-Evans E, Radford JA, Johnson PW. Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. Br J Haematol. 2016 Apr;173(2):274-82. doi: 10.1111/bjh.13954. Epub 2016 Feb 5.

Reference Type: DERIVED

PMID: 26849853 (View on PubMed)

Other Identifiers

USCTU-SCHRIFT-06-DOG05-44

Identifier Type: OTHER

Identifier Source: secondary_id

USCTU-RHM-CAN0542

Identifier Type: OTHER

Identifier Source: secondary_id

2007-000222-51

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EU-20819

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000588042

Identifier Type: -

Identifier Source: org_study_id