Trial Outcomes & Findings for Modified Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) Program for Acute Lymphoblastic Leukemia (NCT NCT00671658)

Last Updated: 2020-12-03

Results Overview

Response - Complete remission (CR): Normalization peripheral blood \& bone marrow 5% or \<blasts in normocellular or hypercellular marrow granulocyte count of 1x10\^9/L or \> \& platelet count \>100x10\^9/L; CR with incomplete platelet recovery (CRp): CR but platelet count \<100x10\^9/L. CR with incomplete recovery (CRi): CR but platelet count \<100x10\^9/L or absolute neutrophil count \< 1x10\^9/L. Partial response (PR): As above except for presence of 6-25% marrow blasts. Lymphoblastic lymphoma (\& ALL subtypes with extramedullary disease): CR - disappearance all known disease. PR - \>50% decrease in tumor size using sum of product, includes 50% volume decrease in lesions measurable in 3 dimensions. No Response (NR) - No significant change (includes stable disease). Lesions decreased size but \<50% or lesions with slight enlargement \<25% increase in size. Progressive Disease (PD): Appearance new lesions, 25% or \> increase in size existing lesions (\>50% if 1 lesion \& \<2).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

220 participants

Primary outcome timeframe

Response assessed following first 21 day course up to end of treatment with 8 cycles, up to 210 days

Results posted on

2020-12-03

Participant Flow

Recruitment Period: 11/02/2002 to 8/28/2012. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	HYPER-CVAD Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Overall Study STARTED	220
Overall Study COMPLETED	215
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	HYPER-CVAD Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Overall Study Physician Decision	5

Baseline Characteristics

Modified Hyper-CVAD (Cyclophosphamide, Vincristine, Adriamycin, and Dexamethasone) Program for Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	HYPER-CVAD n=220 Participants Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Age, Continuous	46 years n=5 Participants
Sex: Female, Male Female	102 Participants n=5 Participants
Sex: Female, Male Male	118 Participants n=5 Participants
Region of Enrollment United States	220 participants n=5 Participants

PRIMARY outcome

Timeframe: Response assessed following first 21 day course up to end of treatment with 8 cycles, up to 210 days

Outcome measures

Outcome measures
Measure	HYPER-CVAD n=215 Participants Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Number of Participants With a Response Complete Response (CR)	198 Participants
Number of Participants With a Response Complete Response without Platelet Recovery	3 Participants
Number of Participants With a Response Partial Response (PR)	4 Participants

Adverse Events

HYPER-CVAD

Serious events: 61 serious events

Other events: 24 other events

Deaths: 25 deaths

Serious adverse events

Serious adverse events
Measure	HYPER-CVAD n=220 participants at risk；n=215 participants at risk Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Eye disorders Vision Loss	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Sepsis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Neutropenic Fever	15.8% 34/215 • Number of events 60 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Blood and lymphatic system disorders Hemorrhage CNS	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Nausea/Vomiting	1.4% 3/215 • Number of events 3 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Infection	14.9% 32/215 • Number of events 54 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Diarrhea	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Nervous system disorders Memory Impairment	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Nervous system disorders Psychosis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Nervous system disorders Seizures	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Musculoskeletal and connective tissue disorders Paraparesis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Cardiac disorders Hypotension	1.4% 3/215 • Number of events 3 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Pain	3.3% 7/215 • Number of events 7 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Nervous system disorders Syncope	1.9% 4/215 • Number of events 5 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Blood and lymphatic system disorders Neutropenia	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Eye disorders Blurred Vision	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Psychiatric disorders Anxiety	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Hepatobiliary disorders Acute Pancreatitis	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Musculoskeletal and connective tissue disorders Arm Fracture	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Death	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Skin and subcutaneous tissue disorders Rash	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Stomatitis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Dehydration	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Respiratory, thoracic and mediastinal disorders Hydro-Pneumothorax	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Musculoskeletal and connective tissue disorders Soft Tissue Necrosis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Colitis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Blood and lymphatic system disorders Fibrinogen decreased	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Metabolism and nutrition disorders Hyperbilirubinemia	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Constipation	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Hemorrhoids	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Flu-Like Syndrome	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Nervous system disorders Neuropathy	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Vascular disorders Thrombosis Embolism	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Abdominal Pain	1.9% 4/215 • Number of events 4 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Hepatobiliary disorders Acute Cholecystitis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Renal and urinary disorders Acute Renal Failure	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Cardiac disorders Atrial Fibrillation	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Back Pain	1.4% 3/215 • Number of events 3 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Blood and lymphatic system disorders Bactremia	0.47% 1/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Bronchitis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Cellulitis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Chest Pain	1.9% 4/215 • Number of events 4 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Respiratory, thoracic and mediastinal disorders Cough	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Duodenal Ulcer	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Vascular disorders Deep Vein Thrombosis	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Fever	1.9% 4/215 • Number of events 5 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Gastrointestinal Rectum Hemorrhage	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Hemorrhage Gastrointestinal	0.47% 1/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Renal and urinary disorders Kidney Stones	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Respiratory, thoracic and mediastinal disorders Lung Hemorrhage	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Mucositis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Skin and subcutaneous tissue disorders Musculoskeletal Soft tissue discomfort	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
General disorders Pain Gallbladder	1.4% 3/215 • Number of events 3 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Partial Small Bowel Obstruction	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Gastrointestinal disorders Perforated Sigmoid Colon	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Pneumonia	0.93% 2/215 • Number of events 2 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Renal and urinary disorders Renal Failure	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Eye disorders Right Eye Retinal Necrosis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Vascular disorders Right Subclavian Thrombosis	0.47% 1/215 • Number of events 1 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.

Other adverse events

Other adverse events
Measure	HYPER-CVAD n=220 participants at risk；n=215 participants at risk Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide (CTX) 300 mg/m\^2 IV, Doxorubicin 50 mg/m\^2 IV, Vincristine 2 mg IV, Dexamethasone 40 mg IV or oral (PO). Methotrexate (MTX) 12 mg intrathecally (6 mg if via Ommaya reservoir) for Courses 1,3,5,7 - 200 mg/m\^2 IV followed by 800 mg/m\^2 for Courses 2,4,6,8. Cytarabine 100 mg intrathecal for Courses 1,3,5,7 - 3 gm/m\^2 IV for Courses 2,4,6,8. G-CSF 10 ug/kg subcutaneous injection. Mesna 600 mg/m\^2 a day IV, Pegylated asparaginase 2000 International units/m\^2 IV. Pegfilgrastim 6 mg (flat dose) within 72 hours after completion of chemotherapy. Solumedrol 40 mg IV for Courses 2,4,6,8.
Gastrointestinal disorders Diarrhea	4.5% 10/220 • Number of events 10 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Neutropenic Fever	10.9% 24/220 • Number of events 24 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Infections and infestations Infection	9.1% 20/220 • Number of events 20 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.
Blood and lymphatic system disorders Neutropenia	5.5% 12/220 • Number of events 12 • Up to 8 cycles of 21 days with 7 day waiting period in between (approximately 28 days) then 30 following last treatment, therefore up to 210 days for completed treatment periods.

Additional Information

Hagop Kantarjian, MD./ Chair

The University of Texas (UT) MD Anderson Cancer Center

Phone: 713-792-7026

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place