Trial Outcomes & Findings for Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL. (NCT NCT00355199)
NCT ID: NCT00355199
Last Updated: 2017-08-10
Results Overview
EFS was defined from the time of the study entry to any treatment failure including disease progression or discontinuation of treatment for any reason or date of the last follow-up visit
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
246 participants
Primary outcome timeframe
36 months from end of therapy
Results posted on
2017-08-10
Participant Flow
Participant milestones
| Measure |
R-HDS
R-HDS: 3 APO: first Doxorubicin at 50 mg/m2 iv, then at 75 mg/m2 iv days 14, 28; Vincristine 1.4 mg/m2 iv days 1,14,28; Prednisone p.o 40 mg/m2 days1-28). Subsequently:high-dose (hd) Cyclophosphamide 7 g/m2 iv, day 1+ Rituximab 375 mg/m2 iv days +3;+11, harvest of peripheral blood progenitor cells (PBPC); hd-Cytarabine 2 g/m2 iv bid for 6 days. Day 7:infusion 1.5-2x10\^6 autologous CD34+ cells/kg, Rituximab 375 mg/m2 iv day+8;+16; hd-Etoposide 2.4 g/m2 iv day +1, Cisplatin 100 mg/m2 iv day+2; PBPC (2x10\^6 CD34+ cells/Kg) reinfused following etoposide/cisplatin. ASCT conditioned with mitoxantrone 60 mg/m2 iv day -5 and melphalan 180 mg/m2 iv day -2 or BEAM (BCNU 300 mg/m2 iv day -6, Etoposide 200 mg/m2 iv days -5 to -2, Ara-C 200 mg/m2 iv every 12 h x8 doses, days from -5 to -2, Melphalan 140 mg/m2 iv day-1),supported by PBPC autograft day 0. Two Rituximab days +14;+24 after ASCT. Patients with initial bulky or residual lesions received IFRT within 2-3 months after chemotherapy program.
|
R-CHOP 14
Patients enrolled into the control arm R-CHOP (rituximab 375 mg/m2 i.v., cyclophosphamide 750 mg/m2 i.v., doxorubicin 50 mg/m2 i.v., vincristine 1.4 mg/m2 i.v. given on day 1 and 100 mg/d of prednisone p.o. on days 1-5), given every 14 days x 8 cycles. The neutropenic phase was supported by G-CSF (filgrastrim 5μg/kg s.c. daily or Pegfilgrastim s.c. given once on day +1 of each cycle). CNS prophylaxis with intrathecal chemotherapy (MTX, ARAC, steroids) was given to high risk patients who, at diagnosis, had infiltration of the bone marrow, testes, Waldeyer ring, cranial air sinuses (including nasal), salivary glands and epidural space. In R-CHOP, 33 patients (27%) received intrathecal prophylaxis. Patients with initial bulky or residual lesions received IFRT within 2-3 months after chemotherapy program.
|
|---|---|---|
|
Overall Study
STARTED
|
120
|
126
|
|
Overall Study
COMPLETED
|
113
|
122
|
|
Overall Study
NOT COMPLETED
|
7
|
4
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Comparison of HD Chemotherapy Followed by Auto-transplant and R-CHOP in High Risk Patients With DLBCL.
Baseline characteristics by cohort
| Measure |
R-HDS
n=113 Participants
R-HDS : Rituximab supplemented high-dose (Cyclophosphamide,Ara-C, Methotrexate, Etoposide, Cis-Platin) sequential chemotherapy with autografting.
Rituximab-HDS: Rituximab-HDS
|
R-CHOP
n=122 Participants
Rituximab-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone).
Rituximab-CHOP: Rituximab-CHOP
|
Total
n=235 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
113 Participants
n=5 Participants
|
120 Participants
n=7 Participants
|
233 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
99 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
65 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
136 Participants
n=5 Participants
|
|
Region of Enrollment
Italy
|
113 participants
n=5 Participants
|
122 participants
n=7 Participants
|
235 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 36 months from end of therapyEFS was defined from the time of the study entry to any treatment failure including disease progression or discontinuation of treatment for any reason or date of the last follow-up visit
Outcome measures
| Measure |
R-HDS
n=113 Participants
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=122 Participants
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Event Free Survival
|
65 percentage of EFS at 3 years follow-up
Interval 56.0 to 74.0
|
62 percentage of EFS at 3 years follow-up
Interval 54.0 to 71.0
|
SECONDARY outcome
Timeframe: Through therapy completion an average of 8 monthsClinical response was assessed by complete restaging according to Cheson criteria. Cheson BD, Pfistner B, Juweid ME, et al: Revised response criteria for malignant lymphoma. J Clin Oncol 25:579-86, 2007
Outcome measures
| Measure |
R-HDS
n=113 Participants
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=122 Participants
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Complete Remission
|
86 participants
|
95 participants
|
SECONDARY outcome
Timeframe: 36 months from end of therapyDFS was defined from the time of documentation of CR to time to relapse or death as a result of lymphoma or acute toxicity of treatment or date of the last follow-up visit
Outcome measures
| Measure |
R-HDS
n=86 Participants
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=95 Participants
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Disease Free Survival
|
91 percentage of DFS at 3 years follow-up
Interval 85.0 to 97.0
|
79 percentage of DFS at 3 years follow-up
Interval 71.0 to 87.0
|
SECONDARY outcome
Timeframe: 36 months from end of therapyOS was defined from the time of the study entry to death as a result of any cause or date of the last follow-up visit
Outcome measures
| Measure |
R-HDS
n=113 Participants
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=122 Participants
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Overall Survival
|
77 percentage of OS at 3 years follow-up
Interval 70.0 to 86.0
|
74 percentage of OS at 3 years follow-up
Interval 67.0 to 82.0
|
SECONDARY outcome
Timeframe: Through therapy completion an average of 8 monthsPercentage of participants with at least one reported episode of CTC grade III or IV toxic events
Outcome measures
| Measure |
R-HDS
n=113 Participants
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=122 Participants
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Toxicity
Grade III or IV Neutropenia
|
84 percentage of participants
|
34 percentage of participants
|
|
Toxicity
Grade III or IV Anemia
|
71 percentage of participants
|
15 percentage of participants
|
|
Toxicity
Grade III or IV Thrombocytopenia
|
86 percentage of participants
|
5 percentage of participants
|
|
Toxicity
Grade III or IV Gastrointestinal
|
29 percentage of participants
|
11 percentage of participants
|
|
Toxicity
Grade III or IV Cardiac
|
4 percentage of participants
|
7 percentage of participants
|
|
Toxicity
Grade III or IV Neurological
|
0 percentage of participants
|
7 percentage of participants
|
|
Toxicity
Grade III or IV Hepatic and Metabolic
|
7 percentage of participants
|
6 percentage of participants
|
|
Toxicity
Grade III or IV Infection
|
54 percentage of participants
|
8 percentage of participants
|
SECONDARY outcome
Timeframe: Through completion of salvage therapyOutcome measures
Outcome data not reported
Adverse Events
R-HDS
Serious events: 29 serious events
Other events: 0 other events
Deaths: 30 deaths
R-CHOP 14
Serious events: 10 serious events
Other events: 0 other events
Deaths: 35 deaths
Serious adverse events
| Measure |
R-HDS
n=113 participants at risk
Patients treated with high dose sequential chemotherapy program (R-HDS) with ASCT.
|
R-CHOP 14
n=122 participants at risk
Patients treated with R-CHOP-14 (8 cycles)
|
|---|---|---|
|
Infections and infestations
Infection
|
14.2%
16/113 • Number of events 28 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
3.3%
4/122 • Number of events 6 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Blood and lymphatic system disorders
Blood/bone marrow cellularity
|
2.7%
3/113 • Number of events 3 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.82%
1/122 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Gastrointestinal disorders
Gastrointestinal
|
2.7%
3/113 • Number of events 3 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.82%
1/122 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Cardiac disorders
Cardiac
|
2.7%
3/113 • Number of events 3 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.00%
0/122 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Nervous system disorders
Neurology
|
1.8%
2/113 • Number of events 2 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.82%
1/122 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Vascular disorders
Hemorrhage/bleeding
|
0.00%
0/113 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.82%
1/122 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary
|
1.8%
2/113 • Number of events 2 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
2.5%
3/122 • Number of events 3 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Renal and urinary disorders
Renal
|
1.8%
2/113 • Number of events 2 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.00%
0/122 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy
|
0.88%
1/113 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.00%
0/122 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Vascular disorders
Vascular
|
0.88%
1/113 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.00%
0/122 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
|
Investigations
Death
|
0.00%
0/113 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
0.82%
1/122 • Number of events 1 • Through therapy scheduled and follow-up completion
Adverse event is any undesirable medical event (symptom or illness, including any abnormal laboratory values), which occurred during treatment or during the follow-up period, regardless of its relationship to treatment in use. Were reported Adverse events with severity \> 2
|
Other adverse events
Adverse event data not reported
Additional Information
Alessandro Rambaldi
Ospedale Papa Giovanni XXIII, Bergamo
Phone: 0352673684
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place