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

Sponsor

University of Southampton (Other)

Overall Status

Terminated

CT.gov ID

NCT00637832

Collaborator

(none)

Enrollment

Locations

Arm

81.2

Actual Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisolone Drug: vincristine sulfate Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

1 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Short Chemo Radiotherapy in Follicular Lymphoma Trial of 90Y Ibritumomab Tiuxetan (ZevalinTM) as Therapy for First and Second Relapse in Follicular Lymphoma

Actual Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Jan 6, 2015

Actual Study Completion Date :

Jan 6, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: single group	Biological: rituximab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisolone Drug: vincristine sulfate Radiation: yttrium Y 90 ibritumomab tiuxetan

Arm

Intervention/Treatment

Experimental: single group

Biological: rituximab

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: prednisolone

Drug: vincristine sulfate

Radiation: yttrium Y 90 ibritumomab tiuxetan

Outcome Measures

Primary Outcome Measures

Overall response rate, including combined complete response and partial response []

Secondary Outcome Measures

Time to disease progression []
Time to next treatment []
Response duration in patients with responding disease []
Safety []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
2	Mount Vernon Cancer Centre at Mount Vernon Hospital	Northwood	England	United Kingdom	HA6 2RN
3	Dorset Cancer Centre	Poole Dorset	England	United Kingdom	BH15 2JB
4	Southampton General Hospital	Southampton	England	United Kingdom	SO16 6YD
5	Saint Bartholomew's Hospital	London		United Kingdom	EC1A 7BE