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

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ClinicalTrials.gov Identifier: NCT03023046
Recruitment Status : Recruiting
First Posted : January 18, 2017
Last Update Posted : October 1, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Washington

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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Philadelphia Chromosome Positive Drug: Cyclophosphamide Drug: Dasatinib Drug: Doxorubicin Drug: Etoposide Drug: Imatinib Mesylate Other: Laboratory Biomarker Analysis Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate Phase 2

Detailed Description:

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 23, 2017
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : December 1, 2022


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.
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Drug: Dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
  • 5-Thiazolecarboxamide
  • Dasatinib Hydrate
  • Dasatinib Monohydrate

Drug: Doxorubicin
Given IV
Other Names:
  • Adriablastin
  • Hydroxyl Daunorubicin
  • Hydroxyldaunorubicin

Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213

Drug: Imatinib Mesylate
Given PO
Other Names:
  • CGP 57148
  • CGP57148B
  • Gleevec
  • Glivec
  • STI 571
  • STI-571
  • STI571

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Prednisone
Given PO
Other Names:
  • .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

Biological: Rituximab
Given IV
Other Names:
  • 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

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine Sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate




Primary Outcome Measures :
  1. Complete minimal residual disease response rate [ Time Frame: Up to 12 weeks ]
    Will be assessed by a Simon two-stage minimax design.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Within 28 days of the last dose of the study drugs ]
    Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Incidence of adverse events will be evaluated.

  2. Next-Generation gene sequencing [ Time Frame: Up to 2 years ]
    Correlations between specific genetic abnormalities and outcome with this treatment will be explored. Reporting will be primarily descriptive, using established statistical methods.

  3. Overall survival [ Time Frame: Up to 2 years ]
    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.

  4. Presence or absence of minimal residual disease [ Time Frame: Up to 2 years ]
    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.

  5. Progression-free survival [ Time Frame: Up to 2 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03023046


Locations
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United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ryan D. Cassaday    206-606-1202    cassaday@seattlecca.org   
Principal Investigator: Ryan D. Cassaday         
Sponsors and Collaborators
University of Washington
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Ryan Cassaday Fred Hutch/University of Washington Cancer Consortium

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Responsible Party: University of Washington
ClinicalTrials.gov Identifier: NCT03023046     History of Changes
Other Study ID Numbers: 9770
NCI-2016-02050 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9770 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
RG1016012 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
First Posted: January 18, 2017    Key Record Dates
Last Update Posted: October 1, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Lymphoma, Non-Hodgkin
Philadelphia Chromosome
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Prednisone
Cortisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Etoposide
Etoposide phosphate
Vincristine
Imatinib Mesylate
Dasatinib
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal