Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

A Phase II Study of Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin (DA-EPOCH) as Front-Line Therapy for Adults With Acute Lymphoblastic Leukemia/Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Etoposide; Drug: Dasatinib; Drug: Cyclophosphamide; Drug: Prednisone; Drug: Vincristine Sulfate; Biological: Rituximab; Drug: Doxorubicin; Drug: Imatinib Mesylate

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16-213; VP-16; VP-16-213; Drug: Dasatinib; Given PO; Other Names: BMS-354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; 5-Thiazolecarboxamide; Drug: Cyclophosphamide; Given IV; Other Names: Cytoxan; CTX; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; Drug: Prednisone; Given PO; Other Names: Deltasone; Orasone; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Panafcort; Panasol-S; Paracort; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisonum; Prednitone; Promifen; Servisone; SK-Prednisone; Drug: Vincristine Sulfate; Given IV; Other Names: Oncovin; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Vincasar; Vincosid; Vincrex; Vincristine, sulfate; Biological: Rituximab; Given IV; Other Names: Rituxan; MabThera; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituximab ABBS; 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; Drug: Doxorubicin; Given IV; Other Names: Adriablastin; Hydroxyl Daunorubicin; Hydroxyldaunorubicin; Drug: Imatinib Mesylate; Given PO; Other Names: Gleevec; CGP 57148; CGP57148B; Glivec; STI 571; STI-571; STI571

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 4 cycles of study therapy
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.	Within 4 cycles of study therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Within 28 days of the last dose of the study drugs
Overall Survival	Alive at 2 years after enrollment	Up to 2 years
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.	Up to 2 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2017
• Primary Completion (Actual): May 20, 2021
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: January 12, 2017
• First Posted (Estimate): January 18, 2017

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: June 18, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Keratolytic Agents; Cyclophosphamide; Etoposide; Etoposide phosphate; Antibodies; Podophyllotoxin; Immunoglobulins; Rituximab; Prednisone; Doxorubicin; Liposomal doxorubicin; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Vincristine; Daunorubicin; Imatinib Mesylate; Cortisone; Dasatinib
• Other Study ID Numbers: 9770 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2016-02050 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); RG1016012 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No