R-CHOP Alone vs. R-CHOP Plus Radiotherapy for Localized CD20+ DLBCL (ASPIRE)

Randomized Phase III Trial Comparing R-CHOP Alone and R-CHOP Plus Radiotherapy for Localized CD20+ Diffuse Large B-cell Lymphoma (DLBCL)

To compare the efficacy and safety of chemotherapy alone and combined modality therapy in the treatment of localized CD20 (+) diffuse large B-cell lymphoma

Study Overview

• Status: Withdrawn
• Conditions: Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Radiation: Radiotherapy; Drug: R-CHOP

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Histologically confirmed CD20-positive Diffuse Large B-cell Lymphoma (DLBCL), NOS
• Immunostains for CD20, CD5, CD3, CD10, MUM-1, BCL-6, BCL-2 and Ki-67 and the in situ hybridization for Epstein-Barr virus are recommended for diagnosis of DLBCL, NOS.
• No prior treatment for DLBCL
• Stage I or contiguous II disease (Involvement of two adjacent lymph node regions or organ involvement with regional lymph nodes)
• Performance status: ECOG 0-2.
• Age ≥ 18 years
• Cardiac ejection fraction ≥ 45% as measured by MUGA or 2D ECHO without clinically significant abnormalities
• Adequate renal function: serum creatinine level < 2 mg/dL
• Adequate liver functions
• Adequate hematological function: hemoglobin ≥ 9.0 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma
• Life expectancy >= 6 months
• A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.
• Female patients of child bearing potential must use an effective method of birth control (i.e. hormonal contraceptive, intrauterine device,diaphragm with spermicide, condom with spermicide or abstinence) during treatment period and 1 month thereafter; Males must use an effective method of birth control during treatment period and 3 months thereafter.

Exclusion Criteria:

• Other subtypes NHL than CD20 (+) DLBCL, NOS
• Transformed DLBCL from follicular lymphoma or other indolent lymphomas
• Bulky disease ( longest diameter >=10 cm)
• Previous treatment for DLBCL with immunotherapy or chemotherapy except for short-term corticosteroids (duration of ≤ 8 days) before inclusion
• CNS involvement by lymphoma or any evidence of spinal cord compression.
• Primary Central Nervous System (CNS) DLBCL
• Primary testicular lymphoma
• Primary breast lymphoma
• Patients with a known history of HIV seropositivity or HCV (+). (Patients who have HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine, etc) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.)
• Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin, early gastric cancer or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 3 years
• Pregnant or lactating women
• Men who are not surgically sterile and women of childbearing potential not employing adequate contraception
• Other serious illness or medical conditions
• Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
• History of significant neurological or psychiatric disorders including dementia or seizures
• Active uncontrolled infection (viral, bacterial or fungal infection)
• Other serious medical illnesses
• Known hypersensitivity to any of the study drugs or its ingredients
• Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Total 6 cycles of R-CHOP	Drug: R-CHOP; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone))
Experimental: Total 3 cycles of R-CHOP + RT; Total 3 cycles of R-CHOP followed by radiotherapy (involved field or involved site radiotherapy, 30-50 Gy/ 15-25 fractions)	Radiation: Radiotherapy; Drug: R-CHOP; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone))

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare 3-year event-free survival	definition of events: failure to achieve CR after completion of planned 1st-line treatment, progression of disease, relapse, institution of a new anticancer treatment or any cause of death) rate in patients with CD20 (+) diffuse large B-cell lymphoma treated with either R-CHOP chemotherapy alone or R-CHOP plus radiotherapy	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate and compare OS between the two arms	3 years
To evaluate and compare the ORR and CR rate	after completion of treatment
To evaluate and compare disease-free survival (DFS)	3 years
To evaluate treatment-failure pattern	3 years
Number of Participants with Adverse Events in each arm	3 years
To assess patient-reported outcomes (PROs) in both arms	3 years
A role of interim PET after 3 cycles of R-CHOP chemotherapy: correlation with PFS and OS	3 years

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2020

Study Registration Dates

• First Submitted: January 29, 2014
• First Submitted That Met QC Criteria: February 2, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Estimate): February 23, 2016
• Last Update Submitted That Met QC Criteria: February 20, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: radiotherapy; localized; diffuse large B-cell lymphoma; R-CHOP chemotherapy
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: AMC_NHL02