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

Primary Purpose

Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cyclophosphamide

Dasatinib

Doxorubicin

Etoposide

Imatinib Mesylate

Laboratory Biomarker Analysis

Prednisone

Rituximab

Vincristine Sulfate

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Overall Survival

Alive at 2 years after enrollment

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.

Full Information

NCT ID

NCT03023046

First Posted

January 10, 2017

Last Updated

June 18, 2022

Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT03023046

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Completed

Study Start Date

February 23, 2017 (Actual)

Primary Completion Date

May 20, 2021 (Actual)

Study Completion Date

May 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Washington

Collaborators

National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment (chemotherapy)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

(-)-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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Dasatinib

Other Intervention Name(s)

BMS-354825, Sprycel, 5-Thiazolecarboxamide, Dasatinib Hydrate, Dasatinib Monohydrate

Intervention Description

Given PO

Intervention Type

Drug

Intervention Name(s)

Doxorubicin

Other Intervention Name(s)

Adriablastin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Imatinib Mesylate

Other Intervention Name(s)

CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571

Intervention Description

Given PO

Intervention Type

Other

Intervention Name(s)

Laboratory Biomarker Analysis

Intervention Description

Correlative studies

Intervention Type

Drug

Intervention Name(s)

Prednisone

Other Intervention Name(s)

.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

Intervention Description

Given PO

Intervention Type

Biological

Intervention Name(s)

Rituximab

Other Intervention Name(s)

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

Intervention Description

Given IV

Intervention Type

Drug

Intervention Name(s)

Vincristine Sulfate

Other Intervention Name(s)

Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Intervention Description

Given IV

Primary Outcome Measure Information:

Title

Number of Participants With Morphological Complete Response Rate

Description

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

Title

Number of Participants With Complete Measurable Residual Disease (MRD) Response Rate

Description

Time Frame

Within 4 cycles of study therapy

Secondary Outcome Measure Information:

Title

Number of Participants With Adverse Events

Description

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

Title

Overall Survival

Description

Alive at 2 years after enrollment

Time Frame

Up to 2 years

Title

Event-free Survival

Description

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ryan D. Cassaday

Organizational Affiliation

Fred Hutch/University of Washington Cancer Consortium

Official's Role

Principal Investigator

Facility Information:

Facility Name

Fred Hutch/University of Washington Cancer Consortium

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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