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

Status: Active

Description

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.

Eligibility Criteria

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

Locations & Contacts

Washington

Seattle
Fred Hutch / University of Washington Cancer Consortium
Status: Active
Contact: Ryan Daniel Cassaday
Phone: 206-606-1202
Email: cassaday@seattlecca.org

Trial Objectives and Outline

PRIMARY OBJECTIVE:

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) receive 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 tyrosine kinase inhibitor (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.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Fred Hutch / University of Washington Cancer Consortium

Principal Investigator
Ryan Daniel Cassaday

Trial IDs

Primary ID 9770
Secondary IDs NCI-2016-02050, RG1016012
Clinicaltrials.gov ID NCT03023046