Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia Clinical Trial

Official title: Phase II Study of Combination of Hyper-CVAD and Dasatinib (NSC-732517) With or Without Allogeneic Stem Cell Transplant in Patients With Philadelphia (Ph) Chromosome Positive and/or BCR-ABL Positive Acute Lymphoblastic Leukemia (ALL) (A BMT Study)

Status Active, not recruiting

Clinical Trial Summary

This phase II trial is studying the side effects of giving combination chemotherapy together with or without donor stem cell transplant and to see how well it works in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect).

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To test whether the relapse-free survival after allogeneic stem cell transplantation among Philadelphia chromosome positive and/or breakpoint cluster region (BCR)/Abelson murine leukemia viral oncogene (ABL) positive acute lymphoblastic leukemia (ALL) patients given an intensive short-term chemotherapy regimen of fractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant further investigation.

SECONDARY OBJECTIVES:

I. To test whether the continuous complete remission rate for previously untreated Philadelphia chromosome positive and/or BCR/ABL positive acute lymphoblastic leukemia (ALL) patients given an intensive short-term chemotherapy regimen of hyper-CVAD in combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant phase III investigation.

II. To investigate in a preliminary manner the relative effectiveness of minimal residual disease (MRD) detection using real-time quantitative polymerase chain reaction (PCR) for BCR/ABL versus flow cytometry to predict the outcome of patients treated by the hyper-CVAD + dasatinib regimen and/or allogeneic stem cell transplant.

TERTIARY OBJECTIVES:

I. To estimate the frequency and severity of toxicities of the intensive short-term chemotherapy regimen in these patients.

II. To estimate the overall survival of all patients on this study.

OUTLINE:

INDUCTION/CONSOLIDATION THERAPY: All patients receive both of the following regimens in alternating courses:

COURSES 1, 3, 5, 7 or 3, 5, 7, 9: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or orally (PO) once daily (QD) on days 1-4 and 11-14; dasatinib PO QD on days 1-14; cytarabine intrathecally (IT) on day 7; methotrexate IT on day 2; and filgrastim (G-CSF) subcutaneously (SC) QD or BID.

COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 24 hours on day 1; methylprednisolone IV over 30 minutes BID on days 1-3; dasatinib PO QD on days 1-14; high-dose cytarabine IV over 2 hours BID on days 2-3; leucovorin calcium IV on days 2 or 3; methotrexate IT on day 2; cytarabine IT on day 7; and G-CSF SC QD or BID.

Treatment repeats every 14-21 days for 8 courses in the absence of disease progression, unacceptable toxicity, or if patient achieves complete remission (CR) or complete remission with incomplete platelet recovery (CRi).

MAINTENANCE THERAPY*: Patients receive vincristine sulfate IV over 30 minutes on day 1, prednisone PO QD on days 1-5, and dasatinib PO QD on days 1-28.

Treatment repeats every month for 24 courses in the absence of disease progression or unacceptable toxicity or until the transplant is ready.

INTENSIFICATION: For courses 6 and 13, patients receive cyclophosphamide IV over 3 hours BID on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or PO QD on days 1-4 and 11-14; dasatinib PO QD on days 1-14; and G-CSF SC QD or BID.

NOTE: *Only if transplantation is not ready after induction/consolidation therapy or patients are not undergoing a transplant.

ALLOGENEIC STEM CELL TRANSPLANTATION (FOR PATIENTS ACHIEVING CR OR CRi):

CONDITIONING REGIMEN: Patients receive 1 of the following regimens:

REGIMEN A: Patients receive total-body irradiation (TBI) QD on days -7 to -4 and cyclophosphamide IV on days -3 and -2.

REGIMEN B: Patients receive TBI BID on days -6 to -4 and cyclophosphamide IV on days -3 and -2.

REGIMEN C: Patients receive cyclophosphamide IV on days -7 and -6 and TBI QD on days -4 to -1.

REGIMEN D: Patients receive cyclophosphamide IV on days -6 and -5 and TBI BID on days -3 to -1.

REGIMEN E: Patients receive TBI QD on days -7 to -4 and etoposide IV on day -3.

REGIMEN F: Patients receive TBI BID on days -6 to -4 and etoposide IV on day -3.

ALLOGENEIC STEM CALL TRANSPLANTATION: Patients undergo allogeneic stem cell transplantation on day 0.

GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive 1 of the following regimens:

REGIMEN A: Patients receive sirolimus PO and tacrolimus IV continuously (changing to PO BID) beginning on day -3 and continuing for 6 months.

REGIMEN B: Patients receive tacrolimus IV continuously (changing to PO BID) and continuing for 6 months, and methotrexate IV on days 1, 3, 6, and 11.

SINGLE-AGENT THERAPY: After completion of maintenance therapy or beginning on day 100 post-transplantation, patients receive dasatinib PO QD for up to 5 years.

After completion of study therapy, patients are followed every 6 months for up to 5 years. ;

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Adult B Acute Lymphoblastic Leukemia
• Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
• Adult L1 Acute Lymphoblastic Leukemia
• Adult L2 Acute Lymphoblastic Leukemia
• Adult T Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
• Recurrent Adult Acute Lymphoblastic Leukemia

• NCT number: NCT00792948
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 1, 2009
• Completion date: January 6, 2025