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| Name | Class |
|---|---|
| Astex Pharmaceuticals, Inc. | INDUSTRY |
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Primary Objective:
1. To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation.
Secondary Objectives:
During the study, patients will have blood, urine, bone marrow, and X-ray exams done. These exams are done to monitor the results of the transplantation. Blood tests will be done daily while patients are hospitalized.
Patients in this study will receive chemotherapy and/or radiation to treat their malignancy and prevent graft rejection. This is given before the infusion of donor cells.
Patients with myeloid leukemias may receive busulfan by vein (IV) for 4 days and cyclophosphamide by vein for 2 days.
Patients with lymphoid malignancies may receive thiotepa by vein in one dose, cyclophosphamide by vein for 2 days, and irradiation for 4 days.
Other chemotherapy treatments may be used before donor cell infusion.
IV injections will be given through a previously inserted catheter that extends into the vena cava (a large chest vein).
Patients will be randomly picked (as in the toss of a coin) to receive one of five different treatments. This is done to learn the benefit of pentostatin treatment and the appropriate dose. Four of the treatments will use different dose schedules of pentostatin. The fifth treatment group will receive no pentostatin at all. All patients receive tacrolimus and methotrexate.
Pentostatin will be given by vein in 4 doses during the first month after transplant. Tacrolimus (FK506) will be given by vein or mouth for 6 months. Methotrexate will be given by vein for 3 doses in the first week after transplant.
Patients will receive blood and platelet transfusions after the transplant. The number of transfusions will depend on how quickly the blood cell counts return to a normal range.
Patients will remain in the hospital for about 4-6 weeks and in the Houston area for 100 days after the transplant.
This is an investigational study. All of the study drugs are commercially available. Pentostatin will not be used for GVHD prevention outside of this study. A total of 150 patients will take part in this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| No Pentostatin | Experimental | Group 1: No Pentostatin |
|
| Pentostatin 0.5 | Experimental | Group 2: Pentostatin 0.5 mg/m^2 |
|
| Pentostatin 1 | Experimental | Group 3: Pentostatin 1 mg/m^2 |
|
| Pentostatin 1.5 | Experimental | Group 4: Pentostatin 1.5 mg/m^2 |
|
| Pentostatin 2 | Experimental | Group 5: Pentostatin 2 mg/m^2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pentostatin | Drug | Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients Without GVHD at 100 Days | The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days. | 100 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marcos de Lima, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| U.T.M.D. Anderson Cancer Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 19654407 | Derived | Parmar S, Del Lima M, Zou Y, Patah PA, Liu P, Cano P, Rondon G, Pesoa S, de Padua Silva L, Qazilbash MH, Hosing C, Popat U, Kebriaei P, Shpall EJ, Giralt S, Champlin RE, Stastny P, Fernandez-Vina M. Donor-recipient mismatches in MHC class I chain-related gene A in unrelated donor transplantation lead to increased incidence of acute graft-versus-host disease. Blood. 2009 Oct 1;114(14):2884-7. doi: 10.1182/blood-2009-05-223172. Epub 2009 Aug 4. |
| Label | URL |
|---|---|
| UT MD Anderson Cancer Center website | View source |
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A total of 150 patients were enrolled, and 147 were available for analysis. Two patients assigned to the 1.5 mg/m^2 arm were removed without receiving treatment (due to ineligibility, and poor donor cell collection). A patient assigned to arm 2.0 mg/m^2 withdrew consent before being treated.
Recruitment Period: September 15, 2000 to July 26, 2007; All recruitment done at UT MD Anderson Cancer Center
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| ID | Title | Description |
|---|---|---|
| FG000 | No Pentostatin | Group 1: No Pentostatin |
| FG001 | Pentostatin 0.5 | Group 2: Pentostatin 0.5 mg/m^2 |
| FG002 | Pentostatin 1 | Group 3: Pentostatin 1 mg/m^2 |
| FG003 | Pentostatin 1.5 | Group 4: Pentostatin 1.5 mg/m^2 |
| FG004 | Pentostatin 2 | Group 5: Pentostatin 2 mg/m^2 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | No Pentostatin | Group 1: No Pentostatin |
| BG001 | Pentostatin 0.5 | Group 2: Pentostatin 0.5 mg/m^2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients Without GVHD at 100 Days | The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days. | All analysis was intention to treat (ITT). | Posted | Number | participants | 100 days |
|
|
7 Years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | No Pentostatin | Group 1: No Pentostatin |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased Creatinine | Renal and urinary disorders | CTCAE (2.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marcos de Lima, MD / Professor | UT MD Anderson Cancer Center | 713-745-3219 | bmcmullin@mdanderson.org |
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| ID | Term |
|---|---|
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D006086 | Graft vs Host Disease |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D015649 | Pentostatin |
| D016559 | Tacrolimus |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D003070 | Coformycin |
| D005573 | Formycins |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
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|
| Tacrolimus | Drug | Given intravenously from day -2, and will be switched to oral dosing when tolerated. |
|
|
| Methotrexate | Drug | Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2. |
|
| Withdrawal by Subject |
|
| BG002 |
| Pentostatin 1 |
Group 3: Pentostatin 1 mg/m^2 |
| BG003 | Pentostatin 1.5 | Group 4: Pentostatin 1.5 mg/m^2 |
| BG004 | Pentostatin 2 | Group 5: Pentostatin 2 mg/m^2 |
| BG005 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
| 0 |
| 27 |
| 28 |
| 37 |
| EG001 | Pentostatin 0.5 | Group 2: Pentostatin 0.5 mg/m^2 | 0 | 10 | 9 | 10 |
| EG002 | Pentostatin 1 | Group 3: Pentostatin 1 mg/m^2 | 0 | 29 | 17 | 29 |
| EG003 | Pentostatin 1.5 | Group 4: Pentostatin 1.5 mg/m^2 | 0 | 61 | 40 | 61 |
| EG004 | Pentostatin 2 | Group 5: Pentostatin 2 mg/m^2 | 0 | 10 | 7 | 10 |
| TTP/HUS | Renal and urinary disorders | CTCAE (2.0) | Systematic Assessment |
|
| CMV | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| bacterial | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| viral | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| parasite | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
| fungal | Infections and infestations | CTCAE (2.0) | Systematic Assessment |
|
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| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003853 | Deoxyribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |