Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia
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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) |
- 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 CCR [ Time Frame: 18 months ] [ Designated as safety issue: No ]Will be estimated using the method of Kaplan-Meier.
- Assessment of transplant being associated with superior RFS [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]Will be estimated using the method of Kaplan-Meier.
| Estimated Enrollment: | 85 |
| Study Start Date: | October 2009 |
| Estimated Primary Completion Date: | June 2014 (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:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Drug: dexamethasone
Given IV or PO
Other Names:
Drug: dasatinib
Given PO
Other Names:
Drug: cytarabine
Given IT
Other Names:
Drug: methotrexate
Given IV or IT
Other Names:
Biological: filgrastim
Given SC
Other Names:
Drug: methylprednisolone
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: prednisone
Given PO
Other Names:
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Drug: etoposide
Given IV
Other Names:
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic stem cell transplant
Procedure: peripheral blood stem cell transplantation
Undergo allogeneic stem cell transplant
Other Names:
Drug: sirolimus
Given PO
Other Names:
Drug: tacrolimus
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 18 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Morphologic diagnosis of acute lymphoblastic leukemia (ALL) with evidence of involvement in bone marrow and/or blood
- No extramedullary disease in the absence of bone marrow or blood involvement
- Philadelphia chromosome (Ph)- and/or BCR/ABL-positive as confirmed by standard cytogenetics, FISH, and/or PCR
- No minimally differentiated acute myeloid leukemia (M0), mixed lineage leukemia, or L3 (Burkitt) ALL
Lineage (B-cell, T-cell, or mixed B/T cell) must be determined
- Appropriate marker studies, including CD19 (B-cell), CD10, CD5, and CD7 (T-cell) must be performed
- Co-expression of myeloid antigens (CD13 and CD33) allowed
- Must be enrolled on clinical trials SWOG-9007, and ECOG-E3903 or CALGB-8461 (for ECOG and CALGB sites)
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 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)
- No active pericardial effusion, ascites, or pleural effusion of any grade
Available matched donor meeting the following criteria:
- Completely matched (i.e., HLA-A, -B, DRβ1) sibling donor OR 10/10-matched non-sibling donor
- Must not be monozygotic identical twin of patient
- Zubrod performance status 0-2
- Bilirubin ≤ 3.0 times upper limit of normal (ULN)
- AST and/or ALT ≤ 3.0 times ULN
- Serum creatinine ≤ 3.0 times ULN
- 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
- HIV-positive patients allowed except in transplantation portion of the study
- No prolonged QTc interval (QTc > 480 msec)
No other prior malignancy except for any of 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
- Any other cancer from which the patient has been disease-free for 5 years
- No known history of type I hypersensitivity or anaphylactic reactions to doxorubicin
- More than 28 days since prior induction chemotherapy
- Collection and submission of pre-treatment cytogenetic specimens must be completed within 28 days prior to registration on S0805
Contacts and Locations
Show 156 Study Locations| 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, S0805, CDR0000624250, U10CA032102 |
| Study First Received: | November 16, 2008 |
| Last Updated: | April 1, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Philadelphia Chromosome 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 Dexamethasone Doxorubicin Etoposide Methylprednisolone Hemisuccinate Prednisolone Prednisone Vincristine Lenograstim Dexamethasone acetate Methylprednisolone acetate Prednisolone acetate Methylprednisolone |
ClinicalTrials.gov processed this record on May 16, 2013