- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02538926
Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
A Phase II Study of Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin Plus Asparaginase (DA-EPOCH-A) for Adults With Acute Lymphoblastic Leukemia/Lymphoma
Study Overview
Status
Conditions
- Recurrent Adult Acute Lymphoblastic Leukemia
- B Acute Lymphoblastic Leukemia
- Recurrent B Lymphoblastic Lymphoma
- Refractory B Lymphoblastic Lymphoma
- B Lymphoblastic Lymphoma
- Recurrent T Lymphoblastic Leukemia/Lymphoma
- Refractory T Lymphoblastic Lymphoma
- T Acute Lymphoblastic Leukemia
- T Lymphoblastic Lymphoma
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the efficacy of dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride plus asparaginase (DA-EPOCH-A) in adults with acute lymphoblastic leukemia/lymphoma (ALL).
SECONDARY OBJECTIVES:
I. To evaluate the safety and feasibility of this regimen.
OUTLINE:
Patients receive etoposide, doxorubicin hydrochloride, and vincristine sulfate intravenously (IV) continuously over days 1-4, cyclophosphamide IV over 1 hour on day 5, and prednisone orally (PO) twice daily (BID) on days 1-5. Patients also receive asparaginase intramuscularly (IM) or IV over 1-2 hours every 2-3 days, beginning day 7 of each course. Patients who are cluster of differentiation (CD)20 positive and Philadelphia chromosome negative also receive rituximab IV on day 1 or 5. Patients who are Philadelphia chromosome positive also receive imatinib mesylate PO on days 1-14. Treatment repeats every 21 days for up to 8 courses 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 then every 6 months for 3 years.
Study Type
Phase
- Phase 2
Contacts and Locations
Study Locations
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients must have a confirmed diagnosis of either B- or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma that is either:
- Arm A: Initially diagnosed at age 40 or later, OR
- Arm B: Relapsed after or failed to respond to >= 1 previous chemotherapy regimen
- The regimen under study must constitute a reasonable therapeutic option
- Presence of >= 5% abnormal blasts in the bone marrow
- Patients with prior allogeneic hematopoietic cell transplantation (HCT) must be at least 90 days post-HCT and must be on =< 20 mg of prednisone (or equivalent dose of an alternative corticosteroid) for treatment/prevention of graft-vs-host disease
- Total bilirubin =< 1.5 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 =< 2.5 x ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x institutional ULN
- Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =< 3.0 x ULN and ALT/AST are =< 5.0 x ULN
- Creatinine =< 1.5 mg/dL; however, patients with a creatinine > 1.5 mg/dL but with a calculated creatinine clearance of > 60 ml/min, as measured by the Modification of Diet in Renal Disease (MDRD) equation, will be eligible
- Measurement of left ventricular ejection fraction (LVEF) should be performed in patients with prior anthracycline exposure or known history of arrhythmia or structural heart disease; in these cases, LVEF must be >= 40%
- 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
- Per good clinical practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with DA-EPOCH-A +/- imatinib (imatinib mesylate) +/- rituximab, should be resolved to grade 1 or less
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
- Women of childbearing potential must have a negative pregnancy test and must agree to the use of effective contraception while on treatment; men must also agree to the use of effective contraception while on treatment
- Ability to give informed consent and comply with the protocol
- Anticipated survival of at least 3 months
Exclusion Criteria:
- Patients with Burkitt lymphoma/leukemia
Patients must not have received chemotherapy within 14 days of enrollment, with the two following exceptions:
- Routine systemic maintenance therapy (e.g., Abelson murine leukemia viral oncogene homolog 1 [ABL] kinase inhibitor, methotrexate, 6-mercaptopurine, vincristine, etc.) and intrathecal/intraventricular therapy
- Systemic therapy for the acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids, cytarabine, etc.)
- May not have prior malignancies unless the expected survival is at least 2 years
- For patients with Philadelphia chromosome positive (Ph+) ALL, they must not have progressed within 3 months of receiving imatinib or have a documented ABL kinase mutation known to confer resistance to imatinib (e.g., T315I)
- Patients with persistent grade 2 or higher peripheral sensory or motor neuropathy of any cause
- Patients with isolated extramedullary disease or with parenchymal central nervous system (CNS) disease
- Known hypersensitivity or intolerance to any of the agents under investigation
Human immunodeficiency virus (HIV) positive or evidence of infection with hepatitis B or C virus, as defined by any of the following criteria (if patients have not previously been tested for the following, these will be conducted during screening):
- HIV antibody positive
- Hepatitis B surface antigen or core antibody positive
- Hepatitis C antibody positive
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (DA-EPOCH-A)
Patients receive etoposide, doxorubicin hydrochloride, and vincristine sulfate IV continuously over days 1-4, cyclophosphamide IV over 1 hour on day 5, and prednisone PO BID on days 1-5.
Patients also receive asparaginase IM or IV over 1-2 hours every 2-3 days, beginning day 7 of each course.
Patients who are CD20 positive and Philadelphia chromosome negative also receive rituximab IV on day 1 or 5. Patients who are Philadelphia chromosome positive also receive imatinib mesylate PO on days 1-14.
Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.
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Correlative studies
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
Given IV
Other Names:
Given IV
Other Names:
Given IM or IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Complete minimal residual disease response rate
Time Frame: Up to 5 years
|
A Simon two-stage optimum design will be used to define success of this treatment in the two subgroups of patients.
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Up to 5 years
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Overall response rate (complete response + partial response)
Time Frame: Up to 5 years
|
A Simon two-stage optimum design will be used to define success of this treatment in the two subgroups of patients.
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Up to 5 years
|
Overall survival
Time Frame: From time of initiation of study therapy to up to 5 years
|
A Simon two-stage optimum design will be used to define success of this treatment in the two subgroups of patients.
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From time of initiation of study therapy to up to 5 years
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Progression-free survival
Time Frame: From time of initiation of study therapy to up to 5 years
|
A Simon two-stage optimum design will be used to define success of this treatment in the two subgroups of patients.
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From time of initiation of study therapy to up to 5 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence of adverse events, graded using the National Cancer Institute Common Terminology Criteria for Adverse Events
Time Frame: Up to 30 days post-treatment, or until patient receives an alternative anti-cancer therapy, whichever date comes first
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Up to 30 days post-treatment, or until patient receives an alternative anti-cancer therapy, whichever date comes first
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ryan Cassaday, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Disease Attributes
- Lymphoma
- Leukemia
- Recurrence
- Lymphoma, Non-Hodgkin
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Lymphoid
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Dermatologic Agents
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Keratolytic Agents
- Cyclophosphamide
- Etoposide
- Etoposide phosphate
- Antibodies
- Podophyllotoxin
- Immunoglobulins
- Rituximab
- Prednisone
- Doxorubicin
- Liposomal doxorubicin
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Vincristine
- Asparaginase
- Imatinib Mesylate
- Cortisone
Other Study ID Numbers
- 9459 (Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium)
- P30CA015704 (U.S. NIH Grant/Contract)
- NCI-2015-01402 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- CC9459
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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