Trial Outcomes & Findings for Rituximab and Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) for Burkitt's and Burkitt's -Like Leukemia/Lymphoma (NCT NCT00669877)
NCT ID: NCT00669877
Last Updated: 2018-05-16
Results Overview
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10\^9/L, a platelet count ≥100 × 10\^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to \<100 × 10\^9/L. Partial remission (PR) was defined as a bone marrow with \>5% and \<25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10\^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
56 participants
Primary outcome timeframe
After two 21-day courses, response to treatment checked for Complete Remission (CR)
Results posted on
2018-05-16
Participant Flow
Recruitment Period: August 15, 2002 to August 28, 2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.
Participant milestones
| Measure |
Hyper-CVAD
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Overall Study
STARTED
|
56
|
|
Overall Study
COMPLETED
|
52
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Hyper-CVAD
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Overall Study
Disease Progression/Death
|
4
|
Baseline Characteristics
Rituximab and Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) for Burkitt's and Burkitt's -Like Leukemia/Lymphoma
Baseline characteristics by cohort
| Measure |
Hyper-CVAD
n=56 Participants
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Age, Continuous
|
41 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After two 21-day courses, response to treatment checked for Complete Remission (CR)Population: Of fifty-six registered, nine participants entered the study with CR therefore were not evaluable for response.
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10\^9/L, a platelet count ≥100 × 10\^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to \<100 × 10\^9/L. Partial remission (PR) was defined as a bone marrow with \>5% and \<25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10\^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR.
Outcome measures
| Measure |
Hyper-CVAD
n=47 Participants
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Complete Remission Rate: Percentage of Participants With Complete Remission (CR)
|
85 percentage of participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: After two 21-day courses, response to treatment checked for Complete Remission (CR)Population: Of fifty-six registered, nine participants entered the study with CR therefore were not evaluable for response.
Complete Remission (CR) was defined as the presence of 5% or less blasts in the bone marrow, with a granulocyte count ≥1.0 × 10\^9/L, a platelet count ≥100 × 10\^9/L, and no extramedullary disease. Complete recovery except platelets (CRp) was defined as for CR, except for recovery of platelet count to \<100 × 10\^9/L. Partial remission (PR) was defined as a bone marrow with \>5% and \<25% blasts with a granulocyte count of ≥1.0 × 109/L and a platelet count of ≥100 × 10\^9/L. Relapse was defined by recurrence of more than 5% lymphoblasts in the bone marrow aspirate or by the presence of extramedullary disease after achieving CR.
Outcome measures
| Measure |
Hyper-CVAD
n=47 Participants
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Overall Response Rate: Percentage of Participants With Complete Remission (CR) or Partial Remission (PR)
|
89 percentage of participants
|
Adverse Events
Hyper-CVAD
Serious events: 27 serious events
Other events: 47 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Hyper-CVAD
n=56 participants at risk
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
48.2%
27/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Urinary Infection
|
3.6%
2/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Pneumonia
|
8.9%
5/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Hepatobiliary disorders
Cholecystitis
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Eye disorders
Cytomegalovirus retinitis (CMV retinitis)
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Blood and lymphatic system disorders
Hemorrhage with Thrombopenia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Psychiatric disorders
Altered Mental Status
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Cardiac disorders
Arrhythmia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Cardiac disorders
Cardiac Ischemia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
General disorders
Death
|
5.4%
3/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Investigations
Fever without neutropenia
|
5.4%
3/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Injury, poisoning and procedural complications
Fracture, Hip
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Nervous system disorders
Hemorrhage, Central Nervous System
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
3.6%
2/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Cardiac disorders
Hypotension
|
3.6%
2/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Infection with neutropenia
|
12.5%
7/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Infection with normal ANC
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Infection without neutropenia
|
5.4%
3/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Infection, Blood
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Infection, wound
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Nervous system disorders
Neuropathy
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Investigations
Non-Neutropenic Fever
|
5.4%
3/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Gastrointestinal disorders
Perforation, GI Small Bowel
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Renal and urinary disorders
Renal Failure
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Nervous system disorders
Seizures
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Vascular disorders
Thrombosis
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
Other adverse events
| Measure |
Hyper-CVAD
n=56 participants at risk
Hyper-CVAD (odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Rituximab 375 mg/m2 days 1 +/- 2 days and 11 +/- 2 days for the odd courses of therapy, and days 1 +/- 2 days and 8 +/- 2 days for the even courses of therapy, first 4 courses. Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3. Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Vincristine 2 mg IV on day 4 +/- 2 days and day 11 +/- 2 days (odd courses). Dexamethasone 40 mg IV or by mouth (P.O.) daily days 1-4 +/- 2 days and days 11-14 +/- 2 days (odd courses). G-CSF 10 mg/kg/day (rounded) until neutrophil recovery 1 x 10\^9/L or higher can be substituted or can be added to pegfilgrastim if neutrophils have not recovered to 1 x 10\^9/L by day 21.
|
|---|---|
|
Infections and infestations
Bacterial Infection
|
28.6%
16/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
General disorders
Fever, Unknown Origin
|
42.9%
24/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Pneumonia, Unknown Pathogen
|
28.6%
16/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Bacterial Pneumonia
|
7.1%
4/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Viral Infection
|
7.1%
4/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Infections and infestations
Non-specified infections
|
7.1%
4/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Investigations
Elevated Alkaline phosphatase (ALT)
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
General disorders
Hemorrhage
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Renal and urinary disorders
Acute Renal Failure
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Gastrointestinal disorders
Mucositis
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Nervous system disorders
Peripheral Neuropathy
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
General disorders
Vomiting
|
3.6%
2/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Gastrointestinal disorders
Constipation
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Gastrointestinal disorders
Ileus
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.8%
1/56 • Adverse events collected through alternating treatment cycles, every 21 days or later to allow for recovery from myelosuppression, for a total of 8 courses or a total of 24 weeks.
|
Additional Information
Naval Daver, Assistant Professor, Leukemia
The University of Texas (UT) MD Anderson Cancer Center
Phone: 1-877-632-6789
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place