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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00792948
First received: November 16, 2008
Last updated: July 28, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention Phase
Adult Acute Lymphoblastic Leukemia in Remission
B-cell Adult Acute Lymphoblastic Leukemia
L1 Adult Acute Lymphoblastic Leukemia
L2 Adult Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
T-cell Adult Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: vincristine sulfate
Drug: dexamethasone
Drug: dasatinib
Drug: cytarabine
Drug: methotrexate
Biological: filgrastim
Drug: methylprednisolone
Drug: leucovorin calcium
Drug: prednisone
Radiation: total-body irradiation
Drug: etoposide
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Drug: sirolimus
Drug: tacrolimus
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Combination of Hyper-CVAD and Dasatinib 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)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Probability of relapse-free survival (RFS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Will be estimated using the method of Kaplan-Meier.

  • Probability of patients being alive and in continuous complete remission (CCR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Will be estimated using the method of Kaplan-Meier.


Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: From the date of initial registration on the study until death from any cause, assessed up to 5 years ] [ Designated as safety issue: No ]
    OS will be estimated using the method of Kaplan-Meier.

  • MRD as assessed using real-time quantitative polymerase chain reaction and flow cytometry [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Correlation between the two measures of MRD measured on the same remission specimens will be examined using scatterplots and correlation analysis. The prognostic effect for relapse of each measure will be illustrated using cumulative incidence plots, and estimated using Cox regression models.


Estimated Enrollment: 85
Study Start Date: September 2009
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (chemotherapy, radiation, transplant)
See Detailed Description
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Drug: dexamethasone
Given IV or PO
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: dasatinib
Given PO
Other Names:
  • BMS-354825
  • Sprycel
Drug: cytarabine
Given IT
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: methotrexate
Given IV or IT
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Biological: filgrastim
Given SC
Other Names:
  • G-CSF
  • Neupogen
Drug: methylprednisolone
Given IV
Other Names:
  • Depo-Medrol
  • Medrol
  • MePRDL
  • Solu-Medrol
  • Wyacort
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: prednisone
Given PO
Other Names:
  • DeCortin
  • Deltra
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic stem cell transplant
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic stem cell transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Drug: sirolimus
Given PO
Other Names:
  • AY 22989
  • Rapamune
  • rapamycin
  • SLM
Drug: tacrolimus
Given IV
Other Names:
  • FK 506
  • Prograf
Other: laboratory biomarker analysis
Correlative studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792948

  Show 160 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Farhad Ravandi-Kashani Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00792948     History of Changes
Other Study ID Numbers: NCI-2009-00800, NCI-2009-00800, CDR0000624250, S0805, S0805, U10CA032102, U10CA180888
Study First Received: November 16, 2008
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia
Leukemia, Lymphoid
Philadelphia Chromosome
Abnormal Karyotype
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Translocation, Genetic
Chromosome Aberrations
Pathologic Processes
Cyclophosphamide
Cytarabine
Methotrexate
Sirolimus
Tacrolimus
Liposomal doxorubicin
Dexamethasone
Doxorubicin
Etoposide
Methylprednisolone Hemisuccinate
Prednisolone
Prednisone
Vincristine
Lenograstim
Dexamethasone acetate
Methylprednisolone acetate

ClinicalTrials.gov processed this record on August 01, 2014