Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
Conditions
Brief summary
This phase II trial studies how well etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin (DA-EPOCH) works in treating patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin, 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.
Interventions
DRUGCyclophosphamide
Given IV
DRUGDasatinib
Given PO
DRUGDoxorubicin
Given IV
DRUGEtoposide
Given IV
DRUGImatinib Mesylate
Given PO
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPrednisone
Given PO
BIOLOGICALRituximab
Given IV
DRUGVincristine Sulfate
Given IV
Sponsors
National Cancer Institute (NCI)
University of Washington
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have a confirmed diagnosis of either: * Acute lymphoblastic leukemia * Lymphoblastic lymphoma with detectable abnormal blasts in the bone marrow * In the opinion of the treating investigator, patients must be an unsuitable candidate for a pediatric-inspired regimen, reasons for which may include (but not be limited to) older age (i.e., \>= 40 years), practical/logistical barriers to or toxicity concerns from administration of a pediatric-inspired regimen, or Ph+ disease * Total bilirubin =\< 2.0 x institutional upper limit of normal (\[ULN\]; unless attributable to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =\< 4.0 x ULN) * Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5.0 x institutional ULN; (Note: patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =\< 5.0 x ULN and ALT/AST are =\< 8.0 x ULN) * Creatinine =\< 2.0 mg/dL; however, patients with a creatinine \> 2.0 mg/dL but with a calculated creatinine clearance of \> 30 ml/min, as measured by the Modification of Diet in Renal Disease (MDRD) equation, will be eligible * As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment; however, adequate recovery of blood counts will be required to receive subsequent cycles) * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2; (performance status of 3 will be allowed if poor performance status is thought to be directly secondary to ALL) * Must agree to the use of effective contraception while on study treatment, unless they are highly unlikely to conceive (defined as \[1\] surgically sterilized, or \[2\] postmenopausal \[i.e., a woman who is \> 50 years old or who has not had menses for \>= 1 year\], or \[3\] not heterosexually active for the duration of the study) * Ability to give informed consent and comply with the protocol * Anticipated survival of at least 3 months, independent of ALL
Exclusion criteria
* Patients with Burkitt lymphoma/leukemia * Patients must not have received any prior systemic therapy for ALL, except for the acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids, cytarabine, etc.) * Patients with isolated extramedullary disease or with known parenchymal central nervous system (CNS) disease * Known hypersensitivity or intolerance to any of the agents under investigation * Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol * May not be pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Morphological Complete Response Rate | Within 4 cycles of study therapy | Morphological complete remission (CR) was determined by bone marrow aspirate morphology and defined as \<5% blasts by morphology, absolute neutrophil count \>1000/uL, and platelet count \>100,000/uL. |
| Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | Within 4 cycles of study therapy | Response was determined by having no detectable disease by multiparameter flow cytometry (MFC-). For Ph+ subjects, complete molecular response (CMR) by BCR-ABL RT-PCR was assigned when MFC was undetectable. When no measurable residual disease was detected by MFC (MFC-) per EuroFlow criteria, high-throughput sequencing-based MRD testing (HTS; ClonoSEQ) was performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | Within 28 days of the last dose of the study drugs | Grade 1 or higher non-hematologic adverse events will be assessed by Common Terminology Criteria for Adverse Events version 5.0. |
| Overall Survival | Up to 2 years | Alive at 2 years after enrollment |
| Event-free Survival | Up to 2 years | Events were defined as any of the following: (1) unable to achieve either morphologic complete remission (CR) or MRD- by MFC, (2) relapse after CR, (3) MRD recurrence after achieving MRD-, or (4) death from any cause. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Chemotherapy) Patients receive etoposide IV over 96 hours, doxorubicin IV over 96 hours, and vincristine sulfate IV over 96 hours on days 1-4. Patients also receive cyclophosphamide IV over 1 hour on day 5 and prednisone PO BID on days 1-5. Patients who are Ph+ also receive imatinib mesylate or dasatinib PO QD on days 1-14. Patients who are CD20+ also receive rituximab IV on day 1 or day 5. Cycles repeat every 21 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity.
Cyclophosphamide: Given IV
Dasatinib: Given PO
Doxorubicin: Given IV
Etoposide: Given IV
Imatinib Mesylate: Given PO
Laboratory Biomarker Analysis: Correlative studies
Prednisone: Given PO
Rituximab: Given IV
Vincristine Sulfate: Given IV | 53 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment (Chemotherapy) |
|---|---|
| Age, Continuous | 49 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| High white blood cell count | 11 Participants |
| Lineage B-cell | 49 Participants |
| Lineage T-cell | 4 Participants |
| Philadelphia chromosome Philadelphia chromosome: negative | 25 Participants |
| Philadelphia chromosome Philadelphia chromosome: positive | 28 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 2 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 | 0 Participants |
| Race (NIH/OMB) White | 46 Participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 18 / 53 |
| other Total, other adverse events | 14 / 53 |
| serious Total, serious adverse events | 32 / 53 |
Outcome results
Primary
Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate
Response was determined by having no detectable disease by multiparameter flow cytometry (MFC-). For Ph+ subjects, complete molecular response (CMR) by BCR-ABL RT-PCR was assigned when MFC was undetectable. When no measurable residual disease was detected by MFC (MFC-) per EuroFlow criteria, high-throughput sequencing-based MRD testing (HTS; ClonoSEQ) was performed.
Time frame: Within 4 cycles of study therapy
Population: HTS- percentages were calculated after excluding patients (Ph+, n = 4; Ph-, n = 3) that were unable to have HTS testing performed for technical reasons.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | HTS- | Achieve within 4 cycles | 8 Participants |
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | MFC- | Achieve within 4 cycles | 20 Participants |
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | HTS- | Not achieved within 4 cycles | 16 Participants |
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | MFC- | Not achieved within 4 cycles | 8 Participants |
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | CMR | Achieve within 4 cycles | 11 Participants |
| Ph+ Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | CMR | Not achieved within 4 cycles | 17 Participants |
| Ph- Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | HTS- | Not achieved within 4 cycles | 16 Participants |
| Ph- Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | MFC- | Achieve within 4 cycles | 16 Participants |
| Ph- Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | HTS- | Achieve within 4 cycles | 6 Participants |
| Ph- Subjects | Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate | MFC- | Not achieved within 4 cycles | 9 Participants |
Primary
Number of Participants With Morphological Complete Response Rate
Morphological complete remission (CR) was determined by bone marrow aspirate morphology and defined as \<5% blasts by morphology, absolute neutrophil count \>1000/uL, and platelet count \>100,000/uL.
Time frame: Within 4 cycles of study therapy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ph+ Subjects | Number of Participants With Morphological Complete Response Rate | 27 Participants |
| Ph- Subjects | Number of Participants With Morphological Complete Response Rate | 20 Participants |
Secondary
Event-free Survival
Events were defined as any of the following: (1) unable to achieve either morphologic complete remission (CR) or MRD- by MFC, (2) relapse after CR, (3) MRD recurrence after achieving MRD-, or (4) death from any cause.
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ph+ Subjects | Event-free Survival | 32 Percentage of Participants |
Secondary
Number of Participants With Adverse Events
Grade 1 or higher non-hematologic adverse events will be assessed by Common Terminology Criteria for Adverse Events version 5.0.
Time frame: Within 28 days of the last dose of the study drugs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ph+ Subjects | Number of Participants With Adverse Events | 44 Participants |
Secondary
Overall Survival
Alive at 2 years after enrollment
Time frame: Up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ph+ Subjects | Overall Survival | 70 Percentage of Participants |