Clinical Trials /

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

NCT03023046

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Lymphoblastic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: 9770
  • SECONDARY ID: NCI-2016-02050
  • SECONDARY ID: 9770
  • SECONDARY ID: P30CA015704
  • SECONDARY ID: RG1016012
  • NCT ID: NCT03023046

Conditions

  • Acute Lymphoblastic Leukemia
  • Lymphoblastic Lymphoma

Interventions

DrugSynonymsArms
Cyclophosphamide(-)-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 MonohydrateTreatment (chemotherapy)
DasatinibBMS-354825, Sprycel, 5-Thiazolecarboxamide, Dasatinib Hydrate, Dasatinib MonohydrateTreatment (chemotherapy)
DoxorubicinAdriablastin, Hydroxyl Daunorubicin, HydroxyldaunorubicinTreatment (chemotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Treatment (chemotherapy)
Imatinib MesylateCGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571Treatment (chemotherapy)
Prednisone.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-PrednisoneTreatment (chemotherapy)
RituximabABP 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 ABBSTreatment (chemotherapy)
Vincristine SulfateKyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateTreatment (chemotherapy)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (chemotherapy)ExperimentalPatients 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.
  • Cyclophosphamide
  • Dasatinib
  • Doxorubicin
  • Etoposide
  • Imatinib Mesylate
  • Prednisone
  • Rituximab
  • Vincristine Sulfate

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete minimal residual disease response rate
Time Frame:Up to 12 weeks
Safety Issue:
Description:Will be assessed by a Simon two-stage minimax design.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Within 28 days of the last dose of the study drugs
Safety Issue:
Description:Will be assessed by Common Terminology Criteria for Adverse Events version 5.0. Incidence of adverse events will be evaluated.
Measure:Next-Generation gene sequencing
Time Frame:Up to 2 years
Safety Issue:
Description:Correlations between specific genetic abnormalities and outcome with this treatment will be explored. Reporting will be primarily descriptive, using established statistical methods.
Measure:Overall survival
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Presence or absence of minimal residual disease
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Progression-free survival
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Washington

Last Updated

December 5, 2019