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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03023046
• Other study ID #: 9770
• Secondary ID: NCI-2016-0205097
• Status: Completed
• Phase: Phase 2
• Start date: February 23, 2017
• Est. completion date: May 1, 2022

Study information

• Verified date: June 2022
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: May 1, 2022
• Est. primary completion date: May 20, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Lymphoblastic Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Cyclophosphamide
Given IV
• Dasatinib
Given PO
• Doxorubicin
Given IV
• Etoposide
Given IV
• Imatinib Mesylate
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Prednisone
Given PO

Biological:
• Rituximab
Given IV

Drug:
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Within 4 cycles of study therapy
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.	Within 4 cycles of study therapy
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.	Within 28 days of the last dose of the study drugs
Secondary	Overall Survival	Alive at 2 years after enrollment	Up to 2 years
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.	Up to 2 years