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

Sponsor

Asan Medical Center (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02054559

Collaborator

(none)

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: R-CHOP Radiation: Radiotherapy	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Jan 1, 2020

Arms and Interventions

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)	Drug: R-CHOP R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone)) Radiation: Radiotherapy

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)

Drug: R-CHOP

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (or prednisolone))

Radiation: Radiotherapy

Outcome Measures

Primary Outcome Measures

To compare 3-year event-free survival [3 years]
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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.