Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia
Condition: 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; Recurrent Adult Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Cyclophosphamide; Cytarabine; Dasatinib; Dexamethasone; Doxorubicin Hydrochloride; Etoposide; Filgrastim; Laboratory Biomarker Analysis; Leucovorin Calcium; Methotrexate; Methylprednisolone; Peripheral Blood Stem Cell Transplantation; Prednisone; Sirolimus; Tacrolimus; Total-Body Irradiation; Vincristine Sulfate
Intervention description: Undergo allogeneic stem cell transplant; Given IV; Given IT; Given PO; Given IV or PO; Given IV; Given IV; Given SC; Correlative studies; Given IV; Given IV or IT; Given IV; Undergo allogeneic stem cell transplant; Given PO; Given PO; Given IV; Undergo TBI; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Sirolimus; Dexamethasone; Dexamethasone acetate; Prednisone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Cortisone; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Dasatinib; Podophyllotoxin; Tacrolimus; Lenograstim; Prednisolone hemisuccinate; Prednisolone phosphate; BB 1101; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 97.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          -  INDUCTION/CONSOLIDATION REGISTRATION:

          -  Patients must have a morphologic diagnosis of acute lymphoblastic leukemia (ALL), with
             evidence of ALL involvement in bone marrow and/or blood; patients with only
             extramedullary disease in the absence of bone marrow or blood involvement are not
             eligible; patients with M0 acute myeloid leukemia (AML) or mixed lineage leukemia are
             not eligible for this study; patients with L3 (Burkitts) are also not eligible

               -  For ALL in marrow or peripheral blood, immunophenotyping of the blood or marrow
                  lymphoblasts must be performed to determine lineage (B cell, T-cell, or mixed B/T
                  cell); NOTE: appropriate marker studies including cluster of differentiation
                  (CD)19 (B cell), CD10, CD5, and CD7 (T cell) must be performed; co-expression of
                  myeloid antigens (CD13 and CD33) will not exclude patients; if possible, the
                  lineage specific markers cytoplasmic CD22 or CD79a (B cells), cytoplasmic CD3 (T
                  cells) and cytoplasmic myeloperoxidase (MPO) (myeloid cells) must be determined

          -  Patients may have received no more than one course of remission induction therapy for
             ALL; patients who have received any post-remission therapy for ALL or who have
             relapsed from complete remission are not eligible; (patients with previously untreated
             ALL can be eligible, and patients who have received one course of remission induction
             therapy for ALL can be eligible, regardless of their response to therapy); patients
             may have received no more than 14 days of tyrosine kinase inhibitor therapy prior to
             registration; any prior induction chemotherapy must have been completed no more than
             28 days prior to registration

               -  NOTE: If the patient has been initiated on the protocol defined regimen (i.e. the
                  hyper-CVAD regimen without a tyrosine kinase inhibitor) before the Philadelphia
                  chromosome (Ph)/BCR-ABL status was known, the patient may be registered on the
                  protocol and start dasatinib; in this first course, dasatinib will be
                  administered up to day 14 (i.e. if the patient is registered on day 5 and starts
                  therapy on day 6, only 8 days of dasatinib will be administered and dasatinib
                  will be completed on day 14)

          -  For patients who have received any prior therapy that was NOT remission induction
             therapy, one of the following must be true:

               -  At least 6 weeks must have elapsed since any monoclonal antibodies were given, at
                  least 7 days must have elapsed since any other treatment was given, and all
                  toxicities of the remission induction therapy must have resolved to grade =< 2

               -  The patient must have rapidly progressive disease (per institutional guidelines)

          -  For previously treated patients, the study chair must be contacted before
             registration, in order to determine the regimen to be given in the first course of
             induction/consolidation therapy, based on prior therapy

          -  Patients must be Philadelphia (Ph) positive and/or BCR/ABL positive as confirmed by
             standard cytogenetics, fluorescent in situ hybridization (FISH), and/or polymerase
             chain reaction (PCR) testing performed by local laboratory; NOTE: samples will be
             submitted centrally for verification of results

          -  Patients must have a bilirubin =< 3.0 x institutional upper limit of normal (IULN)
             within 14 days prior to registration

          -  Patients must have serum glutamic oxaloacetic transaminase (SGOT) (aspartate
             aminotransferase [AST]) =< 3.0 x IULN and/or serum glutamate pyruvate transaminase
             (SGPT) (alanine aminotransferase [ALT]) =< 3.0 x IULN within 14 days prior to
             registration; if both tests are done then both values must be =< 3.0 x IULN

          -  Patients must have a serum creatinine =< 3.0 x IULN within 14 days prior to
             registration

          -  Patients must not have active pericardial effusion, ascites, or pleural effusion of
             any grade; exception: if the effusion is suspected to be related to the leukemia, the
             patient may have pericardial effusion of =< grade 2 or pleural effusion =< grade 1

          -  Patients may not have any clinically significant cardiovascular disease including the
             following:

               -  Myocardial infarction or ventricular tachyarrhythmia within 6 months

               -  Prolonged corrected QT (QTc) >= 480 msec (Fridericia correction)

               -  Ejection fraction less than institutional normal

               -  Major conduction abnormality (unless a cardiac pacemaker is present)

               -  Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of
                  breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with
                  or without stress test as needed in addition to electrocardiogram (EKG) to rule
                  out QTc prolongation; the patient may be referred to a cardiologist at the
                  discretion of the principal investigator; patients with underlying
                  cardiopulmonary dysfunction should be excluded from the study

          -  Patients must have Zubrod performance status of 0-2

          -  No other prior malignancy is allowed except for the following: adequately treated
             basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated
             stage I or II cancer from which the patient is currently in complete remission, or any
             other cancer from which the patient has been disease-free for 5 years

          -  Collection and submission of pre-treatment cytogenetic specimens must be completed
             within 28 days prior to registration on S0805

          -  Collection and submission of pretreatment marrow and/or peripheral blood specimens for
             cellular and molecular studies, including verification of BCR/ABL status must be
             completed within 28 days prior to registration

          -  Patients must not be pregnant or nursing; women/men of reproductive potential must
             have agreed to use an effective contraceptive method; a woman is considered to be of
             "reproductive potential" if she has had menses at any time in the preceding 12
             consecutive months; in addition to routine contraceptive methods, "effective
             contraception" also includes heterosexual celibacy and surgery intended to prevent
             pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy,
             bilateral oophorectomy or bilateral tubal ligation; however, if at any point a
             previously celibate patient chooses to become heterosexually active during the time
             period for use of contraceptive measures outlined in the protocol, he/she is
             responsible for beginning contraceptive measures

          -  Patients must not have prior history of known type I hypersensitivity or anaphylactic
             reactions to doxorubicin

          -  Patients or their legally authorized representative must be informed of the
             investigational nature of this study and must sign and give written informed consent
             in accordance with institutional and federal guidelines

          -  At the time of patient registration, the treating institution's name and
             identification (ID) number must be provided to the Data Operations Center in Seattle
             in order to ensure that the current (within 365 days) date of institutional review
             board approval for this study has been entered into the data base

          -  MAINTENANCE/INTENSIFICATION:

          -  Patient must have achieved CR or CRi within 2 courses of Induction/Consolidation
             Chemotherapy; patient must remain in CR or CRi until beginning Maintenance
             Chemotherapy and this must be re-documented by bone marrow and peripheral blood
             examination within 28 days prior to registration to Step 2

          -  All treatment related toxicities must have resolved to =< grade 2

          -  Patients must not have received allogeneic stem cell transplant

          -  TRANSPLANT REGISTRATION:

          -  Patients must have an available completely matched sibling donor or a 10/10 matched
             non-sibling donor

          -  Patients must have allogeneic stem cell transplant arranged prior to registration to
             Step 3

          -  Patients must have documented CR or CRi within 14 days prior to registration to Step 3

          -  Patients must not be HIV + (human immunodeficiency virus); a negative HIV test must be
             obtained within 14 days prior to registration

          -  POST TRANSPLANT/POST-MAINTENANCE SINGLE-AGENT DASATINIB THERAPY:

          -  Patients must have reached day 100 post transplant or must have completed protocol
             maintenance/intensification (or must have been approved by the Study Chair after early
             removal from maintenance/intensification)

          -  Patients must be in CR or CRi based on bone marrow and peripheral blood examination
             within 28 days prior to registration to Step 4

          -  Patients must have recovered to =< grade 2 from all treatment related toxicity