Trial Outcomes & Findings for Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma (NCT NCT01363128)

Last Updated: 2021-05-03

Results Overview

Complete Remission is Normalization of the peripheral blood and bone marrow with 5% or less blasts in marrow with a granulocyte count of 1 x 109/L or above and a platelet count of 100x 109/L or above. Complete resolution of all sites of extramedullary disease is required for CR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

Up to 8 years

Results posted on

2021-05-03

Participant Flow

Recruitment Period: August 2011 to May 2017

Participant milestones

Participant milestones
Measure	Treatment (Hyper-CVAD, Ofatumumab) COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Overall Study STARTED	69
Overall Study COMPLETED	69
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Combination Chemotherapy and Ofatumumab in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 Participants COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	68 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	41 years n=5 Participants
Sex: Female, Male Female	29 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	53 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	10 Participants n=5 Participants
Region of Enrollment United States	69 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 8 years

Outcome measures

Outcome measures
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 Participants COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Number of Participants With Complete Remission (CR)	68 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Overall Survival is defined as time from date of treatment start until date of death due to any cause or last Follow-up. For continuous data, summary statistics including n, mean, standard deviation, median, minimum and maximum will be computed. The posterior median time to event and it 95% credible interval will be estimated. Kaplan-Meier method, Log rank test and Cox proportional hazards regression modeling will be utilized to analyze survival at 4 years.

Outcome measures

Outcome measures
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 Participants COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
4-Year Overall Survival	47 Participants

PRIMARY outcome

Timeframe: Up to 4 years

Event Free Survival defined as the time from the start of therapy to time of primary refractory disease, relapse from CR, death from any cause or last follow-up. Kaplan-Meier method will be utilized to analyze event free survival for the 4 year percent alive and in CR.

Outcome measures

Outcome measures
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 Participants COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
4-year Event Free Survival	41 Participants

Adverse Events

Treatment (Hyper-CVAD, Ofatumumab)

Serious events: 46 serious events

Other events: 48 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 participants at risk COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Investigations Alanine Aminotransferase Increased	2.9% 2/69 • Number of events 2 • Up to 8 years 9 months
Blood and lymphatic system disorders Anemia	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Infections and infestations Appendicitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Infections and infestations Cellulitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Hepatobiliary disorders Cholecyisitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Colitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Constipation	4.3% 3/69 • Number of events 3 • Up to 8 years 9 months
Gastrointestinal disorders Dehydration	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Diarrhea	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Respiratory, thoracic and mediastinal disorders Dyspena	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Ear and labyrinth disorders Ear Other	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Skin and subcutaneous tissue disorders Erythema Multiforme	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Eye disorders Eye Disorders	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Injury, poisoning and procedural complications Fall	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Blood and lymphatic system disorders Neutropenic Fever	14.5% 10/69 • Number of events 13 • Up to 8 years 9 months
General disorders Fever	10.1% 7/69 • Number of events 8 • Up to 8 years 9 months
Injury, poisoning and procedural complications Fracture	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Gastric Hemorrhage	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Gastrointestinal Disorder	4.3% 3/69 • Number of events 4 • Up to 8 years 9 months
General disorders Headache	2.9% 2/69 • Number of events 2 • Up to 8 years 9 months
Vascular disorders Hypotension	4.3% 3/69 • Number of events 3 • Up to 8 years 9 months
Gastrointestinal disorders Ileus	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Infections and infestations Infection	43.5% 30/69 • Number of events 59 • Up to 8 years 9 months
General disorders Infusion Related Reaction	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Infections and infestations Lung Infection	21.7% 15/69 • Number of events 26 • Up to 8 years 9 months
Infections and infestations Meningitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Metabolism and nutrition disorders Muscle Weakness	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Nausea	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm benign, malignant	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Nervous system disorders Nervous System Disorder	1.4% 1/69 • Number of events 2 • Up to 8 years 9 months
Gastrointestinal disorders Oral Hemorrhage	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
General disorders Pain	7.2% 5/69 • Number of events 5 • Up to 8 years 9 months
Gastrointestinal disorders Pancreatitis	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Vascular disorders Peripheral Ischemia	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Injury, poisoning and procedural complications Postoperative Hemorrhage	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Rectal Hemorrhage	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Renal and urinary disorders Renal and Urinary Disorders	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Reproductive system and breast disorders Reproductive System and Breast Disorders	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Infections and infestations Sepsis	13.0% 9/69 • Number of events 11 • Up to 8 years 9 months
Cardiac disorders Sinus Tachycardia	2.9% 2/69 • Number of events 2 • Up to 8 years 9 months
Infections and infestations Sinusitis	4.3% 3/69 • Number of events 4 • Up to 8 years 9 months
Skin and subcutaneous tissue disorders Skin Lesion	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Nervous system disorders Syncope	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Vascular disorders Thromboembolic Event	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Treatment Related Secondary Malignancy	1.4% 1/69 • Number of events 1 • Up to 8 years 9 months
Gastrointestinal disorders Vomiting	2.9% 2/69 • Number of events 2 • Up to 8 years 9 months

Other adverse events

Other adverse events
Measure	Treatment (Hyper-CVAD, Ofatumumab) n=69 participants at risk COURSES 1, 3, 5, 7: Patients receive hyper-CVAD comprising cyclophosphamide IV over 3 hours every 12 hours on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 15 minutes on days 4 and 11; and dexamethasone IV over 30 minutes or PO QD on days 1-4 and 11-14. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 11 of courses 1 and 3. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 2 hours and then over 22 hours on day 1 and cytarabine IV over 2 hours every 12 hours on days 2-3. Patients also receive ofatumumab IV over 4-6 hours on days 1 and 8 of courses 2 and 4. Treatment repeats every 21-28 days for 8 courses in the absence of disease progression or unacceptable toxicity. Patients may receive maintenance therapy for an additional 30 months. Cyclophosphamide: Given IV Cytarabine: Given IV Dexamethasone: Given IV or PO Doxorubicin Hydrochloride: Given IV Laboratory Biomarker Analysis: Correlative studies Methotrexate: Given IV Ofatumumab: Given IV Vincristine Sulfate: Given IV
Investigations Alanine Aminotransferase Increased	20.3% 14/69 • Number of events 22 • Up to 8 years 9 months
Skin and subcutaneous tissue disorders Alopecia	5.8% 4/69 • Number of events 4 • Up to 8 years 9 months
Blood and lymphatic system disorders Anemia	15.9% 11/69 • Number of events 21 • Up to 8 years 9 months
Investigations Aspartate Aminotransferase Increased	7.2% 5/69 • Number of events 5 • Up to 8 years 9 months
Investigations Blood Bilirubin Increased	5.8% 4/69 • Number of events 4 • Up to 8 years 9 months
Infections and infestations Catheter Related Infection	5.8% 4/69 • Number of events 5 • Up to 8 years 9 months
Gastrointestinal disorders Constipation	7.2% 5/69 • Number of events 5 • Up to 8 years 9 months
Gastrointestinal disorders Diarrhea	8.7% 6/69 • Number of events 7 • Up to 8 years 9 months
Infections and infestations Neutropenic Fever	14.5% 10/69 • Number of events 10 • Up to 8 years 9 months
General disorders Fever	10.1% 7/69 • Number of events 7 • Up to 8 years 9 months
General disorders Headache	10.1% 7/69 • Number of events 8 • Up to 8 years 9 months
Metabolism and nutrition disorders Hyperglycemia	17.4% 12/69 • Number of events 21 • Up to 8 years 9 months
Infections and infestations Infection	11.6% 8/69 • Number of events 10 • Up to 8 years 9 months
Investigations Infusion Related Reaction	17.4% 12/69 • Number of events 13 • Up to 8 years 9 months
Nervous system disorders Insomnia	5.8% 4/69 • Number of events 4 • Up to 8 years 9 months
Gastrointestinal disorders Oral Mucositis	8.7% 6/69 • Number of events 7 • Up to 8 years 9 months
Gastrointestinal disorders Nausea	18.8% 13/69 • Number of events 17 • Up to 8 years 9 months
Investigations Neutropenia	27.5% 19/69 • Number of events 57 • Up to 8 years 9 months
General disorders Pain in Extremity	5.8% 4/69 • Number of events 9 • Up to 8 years 9 months
Nervous system disorders Peripheral Sensory Neuropathy	5.8% 4/69 • Number of events 7 • Up to 8 years 9 months
Investigations Thrombocytopenia	24.6% 17/69 • Number of events 45 • Up to 8 years 9 months
Infections and infestations Sepsis	5.8% 4/69 • Number of events 4 • Up to 8 years 9 months
Infections and infestations Skin Infection	5.8% 4/69 • Number of events 4 • Up to 8 years 9 months
Infections and infestations Upper Respiratory Infection	7.2% 5/69 • Number of events 7 • Up to 8 years 9 months
Gastrointestinal disorders Vomiting	11.6% 8/69 • Number of events 10 • Up to 8 years 9 months

Additional Information

Elias Joseph Jabbour, MD/ Professor

The University of Texas MD Anderson Cancer Center

Phone: 7137924764

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place