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.
Active, not recruiting
Phase 2
| Drug | Synonyms | Arms |
|---|---|---|
| Cyclophosphamide | (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719, Cyclophosphamide Monohydrate | Treatment (chemotherapy) |
| Dasatinib | BMS-354825, Sprycel, 5-Thiazolecarboxamide, Dasatinib Hydrate, Dasatinib Monohydrate | Treatment (chemotherapy) |
| Doxorubicin | Adriablastin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin | Treatment (chemotherapy) |
| Etoposide | Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213 | Treatment (chemotherapy) |
| Imatinib Mesylate | CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571 | Treatment (chemotherapy) |
| Prednisone | .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl, Dacortin, DeCortin, Decortisyl, Decorton, Delta 1-Cortisone, Delta-Dome, Deltacortene, Deltacortisone, Deltadehydrocortisone, Deltasone, Deltison, Deltra, Econosone, Lisacort, Meprosona-F, Metacortandracin, Meticorten, Ofisolona, Orasone, Panafcort, Panasol-S, Paracort, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisonum, Prednitone, Promifen, Servisone, SK-Prednisone | Treatment (chemotherapy) |
| Rituximab | ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83, Rituximab ABBS | Treatment (chemotherapy) |
| Vincristine Sulfate | Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate | Treatment (chemotherapy) |
PRIMARY OBJECTIVES:
I. To examine the potential efficacy of DA-EPOCH as front-line therapy for adults with acute
lymphoblastic leukemia/lymphoma (ALL).
SECONDARY OBJECTIVES:
I. To evaluate the safety and feasibility of this regimen. II. To evaluate the
progression-free (PFS) and overall survival (OS) of patients after receiving DA-EPOCH for
newly-diagnosed ALL.
III. To explore for novel genetic/genomic biomarkers of prognosis and response to treatment
in adults with ALL.
IV. To compare outcomes predicted by the presence or absence of minimal residual disease
(MRD) as determined by either multiparameter flow cytometry (MFC) or high-throughput
sequencing (HTS).
OUTLINE:
Patients receive etoposide intravenously (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 orally (PO) twice a day (BID) on days 1-5. Patients
with disease features that predict sensitivity to ABL kinase inhibitors (e.g., Philadelphia
Chromosome positive (Ph+) [i.e., t(9;22)]; rearrangements involving PDGFRA, PDGFRB, ABL2, or
other genetic lesions that activate kinase receptor signaling): imatinib mesylate or
dasatinib PO once per day (QD) on days 1-14. The decision to add imatinib or dasatinib will
be left to the treating physician and will be based on the available scientific literature to
support the sensitivity of genomic alterations to these TKIs. 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.
After completion of study treatment, patients are followed up every 3 months for 2 years and
every 6 months for 3 years.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Treatment (chemotherapy) | Experimental | 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. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Complete minimal residual disease response rate |
| Time Frame: | Up to 12 weeks |
| Safety Issue: | |
| Description: | Will be assessed by a Simon two-stage minimax design. |
| Measure: | Incidence of adverse events |
| Time Frame: | Within 28 days of the last dose of the study drugs |
| Safety Issue: | |
| Description: | Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Incidence of adverse events will be evaluated. |
| Measure: | Next-Generation gene sequencing |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | Correlations between specific genetic abnormalities and outcome with this treatment will be explored. Reporting will be primarily descriptive, using established statistical methods. |
| Measure: | Overall survival |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | Reporting will be primarily descriptive, with comparisons using established statistical methods. Binary outcomes will be estimated with proportions and associated confidence intervals. Will be estimated using Kaplan-Meier or cumulative incidence estimates. |
| Measure: | Presence or absence of minimal residual disease |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | Will be assessed by multiparameter flow cytometry or high-throughput sequencing. Reporting will be primarily descriptive, with comparisons using established statistical methods. Binary outcomes will be estimated with proportions and associated confidence intervals, time-to-event outcomes will be estimated using Kaplan-Meier or cumulative incidence estimates, as appropriate. Outcomes will be compared between those with and those without minimal residual disease. The chi-square test (or Fisher's exact test) will be used for binary outcomes; the log-rank test will be used for time-to-event outcomes. |
| Measure: | Progression-free survival |
| Time Frame: | Up to 2 years |
| Safety Issue: | |
| Description: | Reporting will be primarily descriptive, with comparisons using established statistical methods. Binary outcomes will be estimated with proportions and associated confidence intervals. Will be estimated using Kaplan-Meier or cumulative incidence estimates. |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | University of Washington |
June 7, 2021
