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Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors Clinical Trials Data presented on Clinical Trials Search isn't meant to be a substitute for qualified health advice, calls or treatment using a genuine doctor. We are not docs. Always consult your dr. on Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors conditions. Clinical Trials Search.org is a site dedicated to listing clinical research studies in human subjects. Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors Clinical research trials and Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors healthcare trials occur in a lot of of places throughout the United States. A clinical trial or clinical study is a research project with human volunteer subjects. Clinical drug trials and pharmaceutical clinical trials generally assess the potency of new drugs. The intent of the studies / undertakings is to figure out certain human medical questions. Clinical trials are a popular means for mDs, government agencies, and private sector corporations to locate remedies for all kinds of circumstances, including Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors. Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors Clinical Trials and other clinical trials allow volunteers to obtain health treatment alternatives before they are available to the masses. Many times the participants undergo treatment for free, and sometimes they are paid for their time. Occasionally there is a cost for a Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors clinical trial. Participants typically obtain the most effective healthcare available for their Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors condition. Dangers are a reality, nonetheless, and can include extra or frequent mD trips, medical hazards (potentially life-endangering), and/or the treatment being uneffective. Trials are federally regulated with rigid guidelines to protect clinical trials patients.
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Home > "E" Clinical Trials Conditions > Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors  Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors
Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors
For Condition: Leukemia
Status: Recruiting
Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) ,
Synopsis: Some high-risk leukemia patients do not have an available family or unrelated donor whose bone marrow is an identical match; their only curative option is to have a transplant from a partially matched family donor. Such transplants are more risky due to an increased risk of graft rejection (loss of the donor's transplanted cells), graft-versus-host disease (injury to healthy tissues from incoming donor cells), and infections which can be fatal. The purpose of this study is to decrease this risk of transplant complications by evaluating a new transplant regimen for high-risk leukemia patients with partially matched related donors. Fifty-one patients between the ages of 10 and 50 will be enrolled in this study. Study participants will receive a preparative regimen consisting of total body irradiation, cyclophosphamide, fludarabine and thiotepa. In order to decrease the risk of graft rejection, patients will receive some additional irradiation to the lymph nodes, called total lymphoid irradiation, as well as two additional medications, cyclosporine and prednisone. Study participants will be followed up for four years to assess long-term disease status and overall survival.
Details: Many patients with malignancies potentially curable by bone marrow transplantation (BMT) are not considered for such treatment because an HLA-identical family or unrelated donor is not available. For these patients, the only curative option is a transplant from a partially HLA-matched related donor (PMRD). Such transplants are feasible but are less successful than matched sibling donor transplants. When the allograft is not T cell depleted, graft-versus-host disease (GVHD) becomes the most significant problem with severe GVHD occurring in about half of the patients. Therefore, T cell depletion is usually performed on the allograft prior to transplant to reduce the risk of GVHD. Although this is a successful strategy for GVHD prophylaxis, T cell depletion results in an increased risk of graft rejection and delayed immune reconstitution, leading to more relapse and post-transplant infectious complications and canceling out any potential benefit of GVHD reduction. The success of PMRD transplants has increased significantly over the last decade due to several recent improvements in the preparative regimen and graft manipulation. The use of high-doses of purified CD34+ hematopoietic progenitor cells combined with a highly immunosuppressive chemoradiotherapy protocol has provided sustained engraftment in over 90 percent of transplant recipients in spite of profound T cell depletion. The incidence of acute and chronic GVHD has been a rare occurrence owing to the success of improvements in T cell depleting technology and the use of pre-transplant anti-thymocyte globulin (ATG). In this setting, the major causes of morbidity and mortality relate to delayed immune reconstitution resulting from the paucity of infused immune cells. We hypothesize that immune recovery following PMRD transplants could be improved by (1) the avoidance of pre-transplant ATG in the preparative regimen (which is known to persist in the blood for 2-4 weeks post-transplant) and (2) the infusion of donor immune cells which have been treated ex vivo to selectively remove alloreactivity. The current protocol will test the first principle - that ATG can be eliminated safely from the preparative regimen without negatively impacting engraftment or GVHD prevention. We will utilize a highly immunosuppressive preparative regimen consisting of fludarabine, cyclophosphamide, thiotepa, and total body irradiation (TBI). This will be followed by a stem cell-rich, T cell-depleted peripheral blood stem cell (PBSC) transplant, containing a CD34 dose of 5 x 106/kg and a CD3 cell dose of less than1 x104 CD3+ cells/kg. Low dose cyclosporine will be given for 3 months following transplant for GVHD prophylaxis. In addition, total lymphoid irradiation (TLI) will be administered the week prior to admission for additional host immunosuppression. The results of this trial will form the basis of the next planned protocol - the addition of donor lymphocytes selectively depleted of alloreactivity to the stem cell inoculum to improve immune reconstitution. This protocol is designed as a pilot study to assess the safety of this novel preparative regimen in patients receiving T cell depleted PBSC transplants from PMRDs. Up to 51 patients will be treated on this protocol. The study will be formally monitored to ensure that serious adverse events, such as acute GVHD, graft failure, and TRM, do not substantially exceed their anticipated rates. Stopping rules will minimize the risk of untoward or unexpected side effects. We will also examine the incidence chronic GVHD, relapse, transplant-related mortality (TRM), disease-free and overall survival. This protocol will be restricted to patients aged 10 to 50 years who are at very high risk of dying from their malignancy. Patients will be followed up for 4 years to assess long-term disease-free and overall survival.
Eligibility:
Study Type: Interventional, Treatment, Safety/Efficacy
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA - Patient: Ages 10-50 years Diagnosed with one of the following Diseases: High-risk myelodysplastic Syndrome (MDS): any of these categories: (1) transformation to acute leukemia (defined as greater than or equal to 15 percent blasts), (2) secondary to prior treatment with chemotherapy and/or radiation, or (3) the presence of complex cytogenetics (greater than or equal to 3 karyotypic abnormalities) or monosomy/deletion of chromosome 7. AML: high-risk patients in first remission (greater than or equal to 3 karyotypic abnormalities, monosomy or deletion of chromosome 5 or 7, 11q23 abnormality, prior diagnosis of MDS, or prior chemotherapy or radiation); all patients in second or subsequent remission; primary induction failure or partial remission; untested or sensitive relapse. CML: (1) blast crisis or (2) accelerated phase disease which has failed treatment with Gleevec, defined as failure to achieve a hematologic response after 3 months of standard-dose therapy (600mg/day) or disease progression on therapy. Myeloproliferative Diseases: diagnosis of agnogenic myeloid metaplasia, essential thrombocythemia, or polycythemia vera, AND evidence of transformation to acute leukemia. ALL: high-risk patients in first remission [t(9;22) or 11q23 chromosomal abnormality, CR greater than or equal to 4 weeks from induction or requiring greater than or equal to 2 induction regimens]. All patients in second or subsequent remission. Access to this protocol is only for patients in whom no better donor alternative (HLA matched related or -unrelated stem cell donor) is available within the time available to perform a transplant before the disease becomes untreatable. Full informed consent from the patient - the patient's decision to proceed with the protocol to be based on the understanding that a better matched donor is unavailable within the time-constraint for performing the transplant before terminal disease progression. No major organ dysfunction precluding transplantation ECOG performance status of 0 or 1 Life expectancy greater than 3 months Ability to comprehend the investigational nature of the study and provide informed consent Availability of an HLA- mismatched family donor, up to 75 years old Women of childbearing age with a negative pregnancy test may participate EXCLUSION CRITERIA - Patient: Any of the following: Pregnant Age less than 10 years or greater than 50 years Availability of a matched related or unrelated donor transplant: (5/6 or 6/6 HLA-matched sibling donor available or unrelated donor search reveals a 6/6 match) ECOG performance status of 2 or more Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible Major anticipated illness or organ failure incompatible with survival from BMT Life expectancy less than 3 months Relapsed leukemia refractory to appropriate salvage therapy Uncontrolled infection DLCO less than 65 percent predicted Left ventricular ejection fraction: less than 40 percent estimated Creatinine greater than 2.0 mg/dl or creatinine clearance less than 60 mL/min Serum bilirubin greater than 4 mg/dl Transaminases greater than 3x upper limit of normal. HIV positive History of other malignancies except basal cell, squamous carcinoma of the skin, remote history of cancer now considered cured, or positive Pap smear and subsequent negative follow up. Failure to collect adequate numbers of CD34+ cells for transplant. INCLUSION CRITERIA - Donor: 3/6 or 4/6 HLA-matched family donor Age 2 to 75 years old Fit to receive G-CSF and give peripheral blood stem cells (normal blood count, normotensive, no history of stroke, no history of severe heart disease) Patients or his/her parents(s)/responsible guardian(s) must be able to comprehend the investigational nature of the study and provide informed consent EXCLUSION CRITERIA - Donor: Any of the following: Pregnant or lactating Age less than 2 or greater than 75 Weight less than or equal 18kg HIV positive. Donors who are positive for HBV, HCV or HTLV-I may be used at the discretion of the investigator following counseling and approval from the recipient. Severe psychiatric illness. Mental deficiency sufficiently severe as to make compliance with the stem cell mobilization and collection unlikely, and making informed consent impossible. Unfit to receive G-CSF and undergo apheresis. (Uncontrolled hypertension, history of stroke, thrombocytopenia)
Total Enrollment: 51
Location and Contact Information:
National Heart, Lung and Blood Institute (NHLBI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 030209; 03-H-0209
Study Start Date: June 9, 2003
Record last reviewed: May 29, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00062725
Other Leukemia Studies:
1. Treatment for Chronic Pain in Patients With Advanced Cancer
2. Blood and Marrow Transplant Clinical Research Network
3. Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma
4. Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
5. Denileukin Diftitox in Treating Patients With Non-Hodgkin's Lymphoma
Related Studies:
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Other Maryland Clinical Trials
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Evaluating a New Transplant Regimen for High-Risk Leukemia Patients with Partially Matched Related Donors
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