Combination Chemotherapy in Treating Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia
This phase II trial studies how well combination chemotherapy works in treating adult patients with newly diagnosed acute lymphoblastic leukemia. Drugs used in chemotherapy 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. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
Inclusion Criteria
- Previously untreated Ph negative precursor B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain; patients who have untreated B-cell or T-cell ALL confirmed by conventional flow cytometry or immunohistochemical stain, but Ph status is unknown, may also enroll
- Patients with T-cell or B cell lymphoblastic lymphoma confirmed by conventional immature T- or pre B cell markers even if the bone marrow is not involved are also eligible
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Serum creatinine =< 2.0 mg/dl or a calculated creatinine clearance of > 60 ml/min
- Total bilirubin < 2.0 mg/dl (unless attributable to Gilbert's disease)
- Alkaline phosphatase =< 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 4 times the upper limit of normal (unless clinically considered to be related to liver involvement with leukemia)
- Left ventricular ejection fraction >= 50% on echocardiogram or multi gated acquisition scan (MUGA) scan
- Negative serum pregnancy test in women of childbearing potential
- Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and at least 4 months after treatment is finished
- Patients with central nervous system involvement by ALL are eligible and may receive concomitant treatment with radiation therapy and/or intrathecal chemotherapy in accordance with standard medical practice; for patients with central nervous system (CNS) disease, dexamethasone may be temporarily administered instead of prednisone to reduce CNS pressure, at the discretion of the treating physician and after discussion with the Memorial Sloan-Kettering (MSK) principal investigator (PI); once dexamethasone is no longer needed, prednisone should be given as per protocol for 28 days
Exclusion Criteria
- Previous treatment for ALL, except for prior steroids and/or hydroxyurea
- Patients known to have Philadelphia (Ph) positive (+) ALL are not eligible; leukemia cell samples will be obtained from all patients enrolled before starting protocol treatment and submitted for Philadelphia chromosome testing by either karyotyping, or breakpoint cluster region (bcr)/Abelson murine leukemia viral oncogene homolog 1 (abl1) translocation by fluorescent in situ hybridization (FISH) or by PCR; patients who are later found to have Ph+ ALL should have treatment on this trial discontinued and will not be considered in the evaluation
- Lymphoid blastic crisis of chronic myelogenous leukemia
- Mature B-cell (Burkitt's) ALL
- Active serious infections not controlled by antibiotics
- Pregnant women or women who are breast-feeding
- Concurrent active malignancy requiring immediate therapy
- Clinically significant cardiac disease (New York [NY] Heart Association class III or IV), including chronic arrhythmia, or pulmonary disease
- Known human immunodeficiency virus (HIV) positive status
- Other serious or life-threatening conditions deemed unacceptable by the principal investigator
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01920737.
PRIMARY OBJECTIVES:
I. To evaluate the efficacy of a novel pediatric-inspired regimen by the rate of molecular remission, i.e. minimal residual disease (MRD) negative status, as assessed by polymerase chain reaction (PCR) and/or flow cytometry in the bone marrow after phase I induction.
SECONDARY OBJECTIVES:
I. To determine the complete remission (CR), overall survival (OS), event-free survival (EFS) disease-free survival (DFS) rates, and MRD status after phase II induction.
II. To confirm the safety and feasibility of the treatment regimen.
TERTIARY OBJECTIVES:
I. To characterize genetic alterations in adult Philadelphia chromosome (Ph) negative acute lymphoblastic leukemia (ALL) patients using high-throughput sequencing technologies.
II. To define genes commonly mutated in ALL that encode proteins rich in the amino acid asparagine.
III. To characterize the role of micro ribonucleic acids (RNAs) in the treatment of adult Ph negative ALL.
IV. To assess the immune competency of the patient receiving maintenance treatment in first CR.
V. To check for development of neutralizing anti asparaginase serum antibodies after each dose of pegaspargase in patients without clinical manifestations of hypersensitivity (i.e. silent hypersensitivity) and patients after clinical allergy.
OUTLINE:
INDUCTION PHASE I (total duration 28 days): Patients receive daunorubicin hydrochloride intravenously (IV) on days 1-3 (in the event of a shortage of daunorubicin hydrochloride, patients may receive doxorubicin hydrochloride as a substitute); vincristine sulfate IV over 1 minute or IV piggyback (IVPB) on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on day 15; prednisone orally (PO) on days 1-28; and methotrexate intrathecally (IT) on days 8 and 15.
INDUCTION PHASE II (total duration 43 days): Beginning 4-12 days after completion of induction phase I, patients receive cyclophosphamide IVPB on days 1 and 29; cytarabine IVPB on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO on days 1-14 and 29-42; vincristine sulfate IV or IVPB on days 1, 15, 29 and 43; pegaspargase IV over 1-2 hours on day 15; prednisone PO on days 15-22; and methotrexate IT on days 1, 15, 29, and 43. Patients achieving CR proceed to intensification therapy.
INTENSIFICATION PHASE I: Patients receive methotrexate IV over 3 hours on days 1 and 15; leucovorin calcium IV every 6 hours beginning 24 hours after the start of each methotrexate dose; pegaspargase IV over 1-2 hours on day 16; and prednisone PO on days 15-22.
RE-INDUCTION PHASE I: Patients receive daunorubicin hydrochloride IV on days 1, 8, and 15 (in the event of a shortage of daunorubicin hydrochloride, patients may receive doxorubicin hydrochloride as a substitute); vincristine sulfate IV or IVPB on days 1, 8, 15, 29, and 43; pegaspargase IV over 1-2 hours on day 15; dexamethasone PO on days 15-22 and 29-36; methotrexate IT on days 1, 8, and 29; cyclophosphamide IVPB on day 29; cytarabine IVPB on days 29-32 and 36-39; and thioguanine PO on days 29-42. Patients who remain in CR then proceed to intensification chemotherapy II after blood count recovers.
INTENSIFICATION PHASE II: Patients receive combination chemotherapy as in Intensification I.
RE-INDUCTION PHASE II: Patients receive combination chemotherapy as in Re-Induction I. Patients continuing to achieve CR proceed to maintenance therapy.
MAINTENANCE (monthly for 36 months): Patients receive prednisone PO on days 1-5 (monthly in first 12 months and every 2 months in months 13-24); vincristine sulfate IV or IVPB on day 1 (monthly in first 12 months and every 2 months in months 13-36); mercaptopurine PO daily on days 1-28; methotrexate PO weekly on days 1, 8, 15, and 22; and methotrexate IT on day 1 (every 3 months during year 1). On days when methotrexate IT is given, methotrexate PO will not be administered.
After completion of study treatment, patients are followed up every month for 6 months, every 3 months for 2 1/2 years, every 6 months for 2 years, and then annually thereafter. At least 3 years of long term follow up must be completed.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJae Park
- Primary ID12-266
- Secondary IDsNCI-2013-01642
- ClinicalTrials.gov IDNCT01920737