AIDS-Related Burkitt Lymphoma, Atypical Burkitt/Burkitt-Like Lymphoma, High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements, High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements, Recurrent Acute Lymphoblastic Leukemia, Recurrent Burkitt Lymphoma, Refractory Acute Lymphoblastic Leukemia, Refractory Burkitt Lymphoma
Conditions
Brief summary
This phase II trial studies how well a dose adjusted regimen consisting of etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (EPOCH) works in combination with ofatumumab or rituximab in treating patients with Burkitt lymphoma that is newly diagnosed, or has returned after a period of improvement (relapsed), or has not responded to previous treatment (refractory) or relapsed or refractory acute lymphoblastic leukemia. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as ofatumumab and rituximab, may interfere with the ability of cancer cells to grow and spread. Giving more than one drug (combination chemotherapy) together with monoclonal antibody therapy may kill more cancer cells.
Detailed description
PRIMARY OBJECTIVE: I. To evaluate the clinical efficacy of the combination of dose adjusted (DA)-EPOCH + ofatumumab in patients with newly diagnosed or relapsed/refractory Burkitt leukemia or relapsed/refractory acute lymphoblastic leukemia (ALL) defined by complete response rate. SECONDARY OBJECTIVE: I. To evaluate the safety of this combination, the overall survival and event-free survival rates. OUTLINE: Patients receive DA-EPOCH regimen comprising doxorubicin hydrochloride intravenously (IV), vincristine sulfate IV, and etoposide IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 1-2 hours on day 5; and prednisone orally (PO) twice daily (BID) on days 1-5. Patients also receive ofatumumab IV over 2 hours on days 1, 2, and 11 of cycle 1; on days 1 and 8 of cycles 2 and 4; and on days 1 and 11 of cycle 3 for a total of 9 injections. Patients may receive rituximab instead of ofatumumab if their insurance provider does not cover the cost of ofatumumab. Patients receive rituximab IV over 2 hours on days 1 and 11 of cycles 1 and 3 and on days 2 and 8 of cycles 2 and 4. Treatment repeats every 21-28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 2-4 months for 1 year and then every 4-8 months for 2 years.
Interventions
DRUGCyclophosphamide
Given IV
DRUGDoxorubicin Hydrochloride
Given IV
DRUGEtoposide
Given IV
BIOLOGICALOfatumumab
Given IV
DRUGPrednisone
Given PO
BIOLOGICALRituximab
Given IV
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Burkitt's or Burkitt-like leukemia/lymphoma, either previously untreated, or relapsed/refractory, or human immunodeficiency virus (HIV)-related; patients with double or triple hit high-grade leukemia/lymphoma are eligible also; patients HIV positive will be described and reported separately or relapsed/refractory acute lymphoblastic leukemia (ALL). * Zubrod performance status =\< 3 (Eastern Cooperative Oncology Group \[ECOG\] scale) * Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related) * Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related) * Adequate cardiac function defined as no history of clinically significant arrhythmia, or history of myocardial infarction (MI) within 3 months prior to study enrollment; cardiac function will be assessed by history and physical examination
Exclusion criteria
* Pregnant or nursing women * Active and uncontrolled disease/infection as judged by the treating physician * Unable or unwilling to sign the consent form * Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With a Response | Up to 8 years | Complete Remission: Normalization of the peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 109/L or above and platelet count of 100 x 10\^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Time | Up to 8 years | Time from date of treatment start until date of death due to any cause or last Follow-up. |
| Event-free Survival | Up to 8 years | Time from date of treatment start until the date of first objective documentation of disease-relapse. |
| Complete Response Duration | Up to 8 years | Response date to loss of response or last follow up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (DA-EPOCH and Ofatumumab or Rituximab) Patients receive DA-EPOCH regimen comprising doxorubicin hydrochloride IV, vincristine sulfate IV, and etoposide IV continuously over 96 hours on days 1-4; cyclophosphamide IV over 1-2 hours on day 5; and prednisone PO BID on days 1-5. Patients also receive ofatumumab IV over 2 hours on days 1, 2, and 11 of cycle 1; on days 1 and 8 of cycles 2 and 4; and on days 1 and 11 of cycle 3 for a total of 9 injections. Patients may receive rituximab instead of ofatumumab if their insurance provider does not cover the cost of ofatumumab. Patients receive rituximab IV over 2 hours on days 1 and 11 of cycles 1 and 3 and on days 2 and 8 of cycles 2 and 4. Treatment repeats every 21-28 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Cyclophosphamide: Given IV
Doxorubicin Hydrochloride: Given IV
Etoposide: Given IV
Ofatumumab: Given IV
Prednisone: Given PO
Rituximab: Given IV
Vincristine Sulfate: Given IV | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Treatment (DA-EPOCH and Ofatumumab or Rituximab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 39 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 4 / 14 |
Outcome results
Primary
Participants With a Response
Complete Remission: Normalization of the peripheral blood and bone marrow with 5% or less blasts in a normocellular or hypercellular marrow with a granulocyte count of 1 x 109/L or above and platelet count of 100 x 10\^9/L or above. Complete resolution of all sites of extramedullary disease is required for CR.
Time frame: Up to 8 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (DA-EPOCH and Ofatumumab or Rituximab) | Participants With a Response | 9 Participants |
Secondary
Complete Response Duration
Response date to loss of response or last follow up.
Time frame: Up to 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (DA-EPOCH and Ofatumumab or Rituximab) | Complete Response Duration | 10.0 Months |
Secondary
Event-free Survival
Time from date of treatment start until the date of first objective documentation of disease-relapse.
Time frame: Up to 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (DA-EPOCH and Ofatumumab or Rituximab) | Event-free Survival | 3.3 Months |
Secondary
Overall Survival Time
Time from date of treatment start until date of death due to any cause or last Follow-up.
Time frame: Up to 8 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (DA-EPOCH and Ofatumumab or Rituximab) | Overall Survival Time | 15.1 Months |