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A Phase III Study of Involved Field Radiation Therapy (IFRT) in Patients With Histologically Aggressive Non-Hodgkin's Lymphoma Following High Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT)


Phase 3
18 Years
N/A
Not Enrolling
Both
Lymphoma

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Trial Information

A Phase III Study of Involved Field Radiation Therapy (IFRT) in Patients With Histologically Aggressive Non-Hodgkin's Lymphoma Following High Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation (ASCT)


OBJECTIVES:

- Compare the 3-year progression-free survival of patients with relapsed or refractory
aggressive non-Hodgkin's lymphoma treated with high-dose chemotherapy and autologous
hematopoietic stem cell transplantation with or without involved-field radiotherapy.

- Compare the overall survival of patients treated with these regimens.

- Compare 3-year progression-free disease within and outside radiotherapy fields in
patients treated with these regimens.

- Compare quality of life of patients treated with these regimens.

- Compare the toxic effects of these regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
response to pre-salvage chemotherapy (primary refractory disease vs relapse), response to
post-salvage chemotherapy (complete/unconfirmed complete vs partial), and participating
center. Within 6-8 weeks after completion of autologous hematopoietic stem cell
transplantation, patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo involved-field radiotherapy (IFRT) 5 days a week for 3-5 weeks
in the absence of unacceptable toxicity.

- Arm II: Patients undergo observation only. Quality of life in arm I is assessed at
baseline, on day 1 of IFRT, at weeks 2 and 4 during IFRT, at 1 month, 4 months, every 3
months for 2 years, every 6 months for 1 year, and then annually for 2 years. Quality
of life in arm II is assessed at baseline, 1 month, 2 months, every 3 months for 2
years, every 6 months for 1 year, and then annually for 2 years.

Patients are followed at 1 month, every 3 months for 2 years, every 6 months for 1 year, and
then annually for 2 years.

PROJECTED ACCRUAL: A total of 230 patients (115 per treatment arm) will be accrued for this
study within 4.2 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed non-Hodgkin's lymphoma

- Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell
lymphoma and T-cell rich B-cell lymphoma)

- Previous indolent lymphoma (follicular center cell lymphoma, marginal zone
lymphoma, including extranodal MALT lymphoma and lymphoplasmacytoid lymphoma)
with transformation to diffuse large B-cell lymphoma at relapse

- Peripheral T-cell lymphoma

- Anaplastic large cell lymphoma (T cell or null cell)

- Small non-cleaved Burkitt-like lymphoma

- Relapsed or refractory disease after first-line anthracycline-based chemotherapy

- Bulky disease, nodal or extranodal

- Clinically or radiographically measurable mass at least 5 cm in diameter OR

- Non-bulky disease, nodal or extranodal, excluding diffuse organ (lung, liver,
kidney, or bone marrow) involvement

- Clinically or radiographically measurable disease more than 1.5 cm in
greatest transverse diameter

- Biopsy at relapse not required except for transformed lymphomas

- Patients with transformed lymphoma at diagnosis, but with indolent histology
without transformation at relapse, are not eligible

- No patients with stage IA or IIA disease at initial diagnosis who, at time of relapse
or diagnosis of refractory disease prior to salvage therapy, remained in stage IA or
IIA, with no new disease sites, without having received radiotherapy

- Received up to 2 regimens and 4 courses of salvage chemotherapy

- Monoclonal antibodies (e.g., rituximab) are not considered salvage chemotherapy

- Achieved complete response (CR), unconfirmed CR, or partial response (PR) if
bulky disease OR

- Achieved PR (but not CR) if non-bulky disease

- No residual disease involving extranodal organs diffusely (e.g., liver, lung, bone,
kidney, or leptomeningeal) after salvage chemotherapy

- Planned autologous hematopoietic stem cell transplantation (ASCT)

- ASCT conditioning must be with high-dose BEAM (carmustine, etoposide,
cytarabine, and melphalan) chemotherapy

- No disease progression after ASCT

- No major organ complication or poor hematologic recovery from ASCT that would
preclude initiation of study radiotherapy within 14 weeks after ASCT

- No more than 2 non-contiguous nodal or extranodal areas of bulky/residual disease
requiring more than 2 separate involved-field radiotherapy volume arrangements (e.g.,
field arrangement covering up to 2 involved lymph node regions or extranodal sites,
with or without 1 adjacent nodal/region or extranodal site)

- No active CNS lymphoma (parenchymal brain and/or leptomeningeal)

PATIENT CHARACTERISTICS:

Age:

- 18 and over

Performance status:

- ECOG 0-2

Life expectancy:

- Not specified

Hematopoietic:

- Not specified

Hepatic:

- Not specified

Renal:

- Not specified

Other:

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No other malignancy within the past 5 years except basal cell carcinoma of the skin

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- See Disease Characteristics

- No prior radioimmunotherapy

Chemotherapy:

- See Disease Characteristics

Endocrine therapy:

- Not specified

Radiotherapy:

- See Disease Characteristics

- No prior total body irradiation

- No prior radiotherapy to the site of bulky disease or residual tumor

Surgery:

- Not specified

Other:

- No other concurrent anti-cancer therapy unless documentation of disease progression

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Principal Investigator

Richard Tsang, MD, FRCPC

Investigator Role:

Study Chair

Investigator Affiliation:

Princess Margaret Hospital, Canada

Authority:

United States: Federal Government

Study ID:

LY8

NCT ID:

NCT00031668

Start Date:

January 2001

Completion Date:

February 2009

Related Keywords:

  • Lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • anaplastic large cell lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin

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