Trial Outcomes & Findings for Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms (NCT NCT00217425)
NCT ID: NCT00217425
Last Updated: 2023-06-18
Results Overview
12-month progression-free survival is defined as the probability of patients remaining alive and progression-free at 12 months from study entry.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
46 participants
Primary outcome timeframe
Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.
Results posted on
2023-06-18
Participant Flow
The first patient was accrued on September 14, 2006.
Participant milestones
| Measure |
Treatment (A-CHOP Followed by MA)
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
Overall Study
STARTED
|
46
|
|
Overall Study
Treated
|
44
|
|
Overall Study
Eligible and Treated
|
39
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
37
|
Reasons for withdrawal
| Measure |
Treatment (A-CHOP Followed by MA)
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
Overall Study
Never started treatment
|
2
|
|
Overall Study
Patient ineligible
|
5
|
|
Overall Study
Lack of Efficacy
|
13
|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Other complicating disease
|
1
|
|
Overall Study
Other
|
4
|
Baseline Characteristics
Bevacizumab and Combination Chemotherapy in Treating Patients With Peripheral T-Cell Lymphoma or Natural Killer Cell Neoplasms
Baseline characteristics by cohort
| Measure |
Treatment (A-CHOP Followed by MA)
n=39 Participants
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
Age, Continuous
|
60 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.Population: Eligible and treated patients
12-month progression-free survival is defined as the probability of patients remaining alive and progression-free at 12 months from study entry.
Outcome measures
| Measure |
Treatment (A-CHOP Followed by MA)
n=39 Participants
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
12-Month Progression-Free Survival (PFS)
|
0.44 probability
Interval 0.31 to 0.63
|
SECONDARY outcome
Timeframe: Assessed after cycle 3, cycle 6, and cycle 8 (if given).Population: Eligible and treated
Overall response rate is defined as proportion of patients who achieve complete remission \[CR, unconfirmed CR (CRu) or Functional CR\] or partial remission. Response is assessed using the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma (Chesen, 1999).
Outcome measures
| Measure |
Treatment (A-CHOP Followed by MA)
n=39 Participants
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
Overall Response Rate
|
0.90 proportion
Interval 0.76 to 0.93
|
SECONDARY outcome
Timeframe: Assessed every 3 months the first 2 years from study entry and every 6 months 3-5 years from study entry.Population: Eligible and treated patients
3-year overall survival is defined as the probability of patients surviving at 3 years from study entry.
Outcome measures
| Measure |
Treatment (A-CHOP Followed by MA)
n=39 Participants
Patients receive 6-8 cycles of bevacizumab and combination chemotherapy comprising cyclophosphamide, doxorubicin, vincristine, and prednisone (A-CHOP) followed by 8 cycles of maintenance bevacizumab (MA), as outlined below. Bevacizumab 15 mg/kg is administered on day 1 over 90 min (first cycle), 60 min (second cycle) and 30 min for the subsequent cycles. CHOP (cyclophosphamide 750 mg/m 2 ; doxorubicin 50 mg/m 2 ; vincristine 1.4 mg/m2 \[max. 2 mg\]; prednisone 100 mg daily on days 1-5) is administered on day 1 of a 21-day cycle. Radiographic response is assessed after cycles 3, 6 and 8 of ACHOP and after cycle 8 of MA. Patients receive six cycles of ACHOP if they achieve a complete response (CR) after three cycles, eight cycles if they achieve a partial response (PR) after three cycles. Non-responders are removed from the study. ACHOP responders receive maintenance bevacizumab 15 mg/kg every 21 days for eight cycles.
|
|---|---|
|
3-Year Overall Survival
|
0.39 probability
Interval 0.26 to 0.58
|
Adverse Events
Treatment (ACHOP Followed by MA)
Serious events: 34 serious events
Other events: 39 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (ACHOP Followed by MA)
n=44 participants at risk
Adverse events in all treated patients regardless of eligibility.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
31.8%
14/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count decreased
|
27.3%
12/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Neutrophil count decreased
|
52.3%
23/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
11.4%
5/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Cardiac disorders
Ventricular arrhythmia
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypertension
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypotension
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Cardiac disorders
Left ventricular systolic dysfunction
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Cardiac disorders
Restrictive cardiomyopathy
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fatigue
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Weight loss
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Death NOS
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Colitis
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Constipation
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Mucositis oral
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Colonic perforation
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Intra-abdominal hemorrhage
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
18.2%
8/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Infections and infestations - Other, spe
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Lung infection
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Anorectal infection
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Infections and infestations
Urinary tract infection
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Aspartate aminotransferase increased
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Blood bilirubin increased
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.5%
2/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
4.5%
2/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Investigations - Other, specify
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Esophageal pain
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Headache
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.5%
2/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Reproductive system and breast disorders
Vaginal inflammation
|
2.3%
1/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Thromboembolic event
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
Other adverse events
| Measure |
Treatment (ACHOP Followed by MA)
n=44 participants at risk
Adverse events in all treated patients regardless of eligibility.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Blood and lymphatic system disorders
Anemia
|
34.1%
15/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
White blood cell decreased
|
15.9%
7/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Lymphocyte count decreased
|
18.2%
8/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Neutrophil count decreased
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Platelet count decreased
|
15.9%
7/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Vascular disorders
Hypertension
|
11.4%
5/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fatigue
|
65.9%
29/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Fever
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Psychiatric disorders
Insomnia
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Weight loss
|
27.3%
12/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
11.4%
5/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
38.6%
17/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Anorexia
|
27.3%
12/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Constipation
|
31.8%
14/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Diarrhea
|
20.5%
9/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Abdominal distension
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Gastritis
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
20.5%
9/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Mucositis oral
|
11.4%
5/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Nausea
|
34.1%
15/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dysgeusia
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
18.2%
8/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Bronchopulmonary hemorrhage
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
General disorders
Edema limbs
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Alkaline phosphatase increased
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Alanine aminotransferase increased
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Aspartate aminotransferase increased
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
43.2%
19/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hypokalemia
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Renal and urinary disorders
Proteinuria
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Metabolism and nutrition disorders
Hyponatremia
|
15.9%
7/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Investigations
Investigations - Other, specify
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Dizziness
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
54.5%
24/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Eye disorders
Watering eyes
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
4/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Nervous system disorders
Headache
|
11.4%
5/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
13.6%
6/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
15.9%
7/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Voice alteration
|
6.8%
3/44 • Assessed every 3 weeks while on treatment and for 30 days after the end of treatment
|
Additional Information
Study Statistician
ECOG Statistical Office
Phone: 617-632-3012
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place