Combination Chemotherapy and Nelarabine in Treating Patients With T-cell Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma
Study Details
Study Description
Brief Summary
This phase II trial studies the side effects and how well combination chemotherapy and nelarabine work in treating patients with T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy, such as cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine, mercaptopurine, prednisone, pegaspargase, nelarabine, and venetoclax 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 |
|---|---|---|
|
Phase 2 |
Detailed Description
PRIMARY OBJECTIVES:
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To determine the complete remission (CR) rate and progression-free survival following treatment with hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with nelarabine in previously untreated patients with T-cell acute lymphoblastic leukemia (ALL) and T-cell lymphoblastic lymphoma.
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To determine the safety and overall survival of previously untreated patients with T-cell ALL and T-cell lymphoblastic lymphoma.
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To determine the safety and efficacy of adding pegaspargase to the regimen.
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To determine the safety and efficacy of adding venetoclax to the regimen.
OUTLINE:
COURSES 1, 3, 5, and 7 (hyper-CVAD): Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on day 1-3, doxorubicin IV over 24 hours on day 4, vincristine IV over 15-30 minutes on days 4 and 11, and dexamethasone IV or orally (PO) once daily (QD) on days 1-4 and 11-14.
COURSES 2, 4, 6, and 8 (methotrexate/cytarabine): Patients receive methotrexate IV over 24 hours on day 1 and cytarabine IV over 2 hours BID on days 2 and 3.
Patients also receive venetoclax PO QD on days 1-14 of each course. Courses of hyper-CVAD and methotrexate/cytarabine repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients also receive nelarabine IV over 2 hours once daily (QD) for 5 days and pegaspargase IV over 2 hours on day 5 after completion of course 4 and after the completion of course 5 in the absence of disease progression or unacceptable toxicity.
MAINTENANCE COURSES 1-5, 8-17, and 20-30 (mercaptopurine, vincristine, methotrexate, and prednisone [POMP]): Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO once weekly, vincristine sulfate IV on day 1, prednisone PO QD on days 1-5, and venetoclax PO QD on days 1-7. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
INTENSIFICATION COURSES 6 and 7: Patients receive nelarabine IV QD over 2 hours on days 1-5 and pegaspargase IV over 2 hours on day 5. Patients also receive venetoclax PO QD on days 1-14. Courses repeat every 21-35 days in the absence of disease progression or unacceptable toxicity.
INTENSIFICATION COURSES 18 and 19: Patients receive methotrexate IV over 2 hours on day 1, pegaspargase IV over 2 hours on day 2, and venetoclax PO QD on days 1-14 in the absence of disease progression or unacceptable toxicity.
POMP maintenance therapy continues for 30 months in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment (nelarabine and combination chemotherapy) See Detailed Description |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IV
Other Names:
Drug: Dexamethasone
Given IV or PO
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IV and PO
Other Names:
Drug: Nelarabine
Given IV
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Drug: Prednisone
Given PO
Other Names:
Drug: Venetoclax
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Complete remission rate [3 years]
The sample size will provide an estimate of relapse rate at 3 years with a 95% confidence interval of width +/- 10%.
- Duration of remission [Up to 9 years]
Duration of remission will be evaluated.
- Progression-free survival [3 years]
Progression-free survival will be estimated.
- Overall survival [3 years]
Overall survival will be estimated.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Previously untreated T cell ALL including T cell lymphoblastic lymphoma; failure to one induction course of chemotherapy are eligible; patients in CR after =< 2 courses are also eligible
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Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 3
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Serum bilirubin less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 5.0 mg/dL is acceptable
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Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) less than or equal to 4 x upper limit of normal (ULN)
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Serum creatinine less than or equal to 2.0 mg/dL unless considered due to involvement by tumor when an upper limit of 2.5 mg/dL is acceptable
Exclusion Criteria:
- Pregnant or nursing women
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | M D Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Farhad Ravandi-Kashani, M.D. Anderson Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 2006-0328
- NCI-2012-01518
- 2006-0328