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Study Summary
No. SWOG0805:.......Leukemia......Farhad Ravandi-Kashani......Leukemia
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Study Summary Title
Study Summary
Number:
SWOG0805
Study 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).
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Physician New Patient Referral
Name:Farhad Ravandi-KashaniPatients Call:800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Dept:LeukemiaReferring MD
Call:
800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)
Phone:713-792-7305
Contact us about clinical trials
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General Information
Disease Group:LeukemiaSupported By:CTEP/SWOG
Phase of Study:Phase IIReturn
Visit:
at least twice weekly for the entire length of the intensive phase, then at
least once monthly during maintenance, more frequent during transplant phase
Treatment
Agents:
Dasatinib
Hyper-CVAD
None
Pegfilgrastim
Stem Cell Transplantation
Home Care:None
Treatment Loc:Only at MDACC
Estimated
Length of Stay
in Houston:
approximately one week every 3 weeks up to a maximum of 8; additional
hospitalizations for complications , as needed
Description/
Intervention:
The goal of this clinical research study is to learn if dasatinib can help to
control ALL when given with the standard of care and/or a stem cell transplant.
The safety of this drug will also be studied.
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Study Objectives / Outcomes
To test whether the relapse-free survival after allogeneic stem cell transplantation among Philadelphia chromosome positive and/or BCR/ABL positive acute lymphblastic lekemia (ALL) patients given an intensive short-term chemotherpay regimen of hyper-CVAD in combination withte tryrosine kinase inhibitor dasatinib is sufficiently high to warrant further investigation

To test whether the continous complete remission rate for previousl y untreated Philadelphia chromosome positive and/or BCR/ABL positive acute lymphoblastic (ALL) patients given an intensive short-term chemotherapy regimen of hyper-CVAD in combination with the tyrosine inhibitor dasatinib is sufficiently hight to warrant Phase III investigation.

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

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

To estimate the overall survival of all patients on this study.
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Study Status Information
Study Activation / Registration Date:
IRB Review and Approval Date:12/01/2010
Study Type:Phase Ii Or Phase I/Ii
Recruitment Status:Open
Projected Accrual:85
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Enrollment Eligibility
If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:1) Patients must have morphologic diagnosis of acute lymphoblastic leukemia (ALL), as defined in Section 4.1b 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 AML or mixed lieage leukemia are not eligible for this study. patients with L3(Burkitts) are also not eligible.

2) Continuation of No. 1 - For ALL in marrow or perpheral blood, immunophnotyping of the blood or marrow lymphblasts must be perfomed to determine lieage (B cell, T-cell, or misxed B/T cell),. NOTE: Appropriate marker studies including CD19 (B cell), CD10, CD5, and CD7 (T cell) must be performed. Coexpression 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 (MPR) (myeloid cells) must be determined.

3) Patients (PTs) may have received no more than 1 course of remission induction therapy for ALL, providing this induction course was given prior to the results of the cytogenetics testing for Ph/BCR/ABL status being known. PTs who have received any post-remission therapy for ALL or who have relapsed from complete remission are not eligible. (PTs w/ previously untreated ALL can be eligible, & PTs who have received one course of remission induction therapy for ALL can be eligible, regardless of their response to therapy.) Any prior induction chemotherapy must have been completed no more than 28 days prior to registration.

4) Continuation of # 3 ------- NOTE: if the patient has been initiated on the protocol defined regimen (i.e. the hyperCVAD regimen without a Tyrosine kinase inhibitor) before the 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).

5) For patients who have received any prior therapy that was NOT remission induction therapy, one of the following must be true: 1.) 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 less than or equal to 2; or 2.) The patient must have rapidly progressive disease (per institutional guidelines).

6) Induction/ Consolidation Registration (Registration Step 1)- For previously treated patients, the Study Coordinator 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.

7) Induction/Consolidation Registration (Registration Step 1) - Patients must be Philadelphia (Ph) chromosome positive and/or BCR/ABL positive as confirmed by standard cytogenetics, Fluorescence in situ Hybridization (FISH), and/or PCR testing performed by local laboratory. NOTE: Samples will be submitted centrally for verification of results

8) Induction/Consolidation Registration (Registration Step 1) - Patients must have a bilirubin less than or equat to 3.0 x Institutional Upper Limit of Normal (IULN) within 14 days prior to registration.

9) Induction/Consolidation Registration (Registration Step 1) - Patients must have SGOT (AST) less than or equal to 3.0 x upper limit of normal (IULN) and/or SGPT (ALT) less than or equal to 3.0 x IULN within 14 days prior to registration.

10) Induction/Consolidation Registration (Registration Step 1) - Patients must have a serum creatinine less than or equal to 3.0 x IULN within 14 days prior to registration.

11) Induction/Consolidation Registration (Registration Step 1) - 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 < or equal to Grade 2 or pleural effusion < or equal to Grade 1.

12) Induction/Consolidation Registration (Registration Step 1) - Patients must have Zubrod Performance Status of 0-2.

13) Induction/Consolidation Registration (Registration Step 1) - Patients must be greater than or equal to 18 and less than or equal to 60 years of age.

14) Induction/Consolidation Registration (Registration Step 1) - 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.

15) Induction/Consolidation Registration (Registration Step 1) - Collection of pretreatment marrow specimens must be completed within 28 days prior to registration. Pretreatment specimens of bone marrow (or peripheral blood if the marrow aspirate is a dry tap) must be submitted to the site's preferred CLIA-approved cytogenetics laboratory (see protocol sections 9.1 and 15.1a). Reports of the results must be submitted as described in protocol section 14.0. Note that cytogenetics are required at other timepoints (see protocol section 9.1-9.4)

16) ECOG sites: Cytogenetic studies are performed locally. Prior to registration on S0805 ECOG patients must be registered on E3903, Ancillary laboratory protocol for collecting diagnostic material on patients considered for ECOG treatment trials for leukemia or erlated hematologic disorders. Karyotypes and FISH reports must be submitted for central review, via E3903, to the Mayo Clinic Cytogenetics Laboratory in Rochester. Note that S0805 also requires the submission of follow-up cytogenetics.

17) Induction/Consolidation Registration (Registration Step 1) - PTs must be registered on CALGB-8461 ("Cytogenetic Studies in Acute Leukemia"). Pretreatment specimens must be submitted as outlined in CALGB-8461 and for cytogenetic analysis. Note that protocol CALGB-8461 also requires submission of remission and relapse specimens.

18) Induction/Consolidation Registration (Registration Step 1) - Patients must not be pregnant or nursing because of the teratogenic potential of the drugs used in this study. 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.

19) Induction/Consolidation Registration (Registration Step 1) - Patients must not have prior history of known Type I hypersensitivity or anaphylactic reactions to doxorubicin.

20) Induction/Consolidation Registration (Registration Step 1) - All patients 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.

21) Induction/Consolidation Registration (Registration Step 1) - At the time of patient registration, the treating institution's name and 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.

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Criteria truncated, please contact Prinicipal Investigator's office for full criteria

Exclusion Criteria:1) Induction/Consolidation Registration (Registration Step 1) - Patients must not have active pericardial effusion, ascites, or pleural effusion of any grade, or prolonged QTc interval (QTc > 480 msec).

2) Induction/Consolidation Registration (Registration Step 1) - Patients must not be pregnant or nursing because of the teratogenic potential of the drugs used in the is study. Women/men of reproductive potential must have agreed to use an effective contraceptive method. Women of reproductive potential must have a negative pregnancy test performed within 14 days prior to registration.

3) Induction/Consolidation Registration (Registration Step 1): Patients must not have prior history of known Type I hypersensitivity of anaphylactic reactions to doxorubicin.

4) Donors must not be monozygotic identical twins of their recipients.

5) Donors must not be pregnant or breastfeeding.

6) Donors must not have sensitivity to filgrastim or E. coli-derived recombinant protein products.

7) Donors must not have HIV, HBV, or HCV infection.

8) Donors must not have thrombocytopenia less than 150 x 10(9)/L (less than 150,000/mcl) at baseline.

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Links
Registration Number: NCT00792948
Study Information on Clinical Trials Registry (clinicaltrials.gov)

Other Links:
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Results


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