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

NCT03023046 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: 9770NCI-2016-02050P30CA015704RG1016012
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Lymphoblastic Leukemia; Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (3)

• Number of Participants With Adverse Events

  Within 28 days of the last dose of the study drugs

• Overall Survival

  Up to 2 years

• Event-free Survival

  Up to 2 years

Study Arms (1)

Treatment (chemotherapy)

EXPERIMENTAL

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; Drug: Dasatinib; Drug: Doxorubicin; Drug: Etoposide; Drug: Imatinib Mesylate; Other: Laboratory Biomarker Analysis; Drug: Prednisone; Biological: Rituximab; Drug: Vincristine Sulfate

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (chemotherapy)

Dasatinib DRUG

Given PO

Also known as: BMS-354825, Sprycel, 5-Thiazolecarboxamide, Dasatinib Hydrate, Dasatinib Monohydrate

Treatment (chemotherapy)

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Treatment (chemotherapy)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (chemotherapy)

Imatinib Mesylate DRUG

Given PO

Also known as: CGP 57148, CGP57148B, Gleevec, Glivec, STI 571, STI-571, STI571

Treatment (chemotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy)

Prednisone DRUG

Given PO

Also known as: .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

Treatment (chemotherapy)

Rituximab BIOLOGICAL

Given IV

Also known as: 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

Treatment (chemotherapy)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

Treatment (chemotherapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; Dasatinib; Doxorubicin; Etoposide; Imatinib Mesylate; Prednisone; deltacortene; prednylidene; Rituximab; CT-P10; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Piperazines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Limitations and Caveats

The sample sizes in this study are relatively small, making it difficult to draw definitive conclusions regarding response rate and survival with this regimen.

Results Point of Contact

• Title: Ryan Cassaday, MD
• Organization: University of Washington

cassaday@seattlecca.org

2066061202

Study Officials

• Ryan D. Cassaday

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Division of Hematology

Study Record Dates

• First Submitted: January 10, 2017
• First Posted: January 18, 2017
• Study Start: February 23, 2017
• Primary Completion: May 20, 2021
• Study Completion: May 1, 2022
• Last Updated: July 13, 2022
• Results First Posted: July 13, 2022

Record last verified: 2022-06

Locations

US (1)