NCT01203722已完成1 期
Reduced Intensity, Partially HLA Mismatched Allogeneic BMT for Hematologic Malignancies Using Donors Other Than First-degree Relatives
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins1 个研究点 分布在 1 个国家目标入组 87 人开始时间: 2010年9月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 87
- 试验地点
- 1
- 主要终点
- Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD)
研究概览
简要总结
If transplantation using mismatched unrelated donors or non-first-degree relatives could be performed with an acceptable toxicity profile, an important unmet need would be served. Towards this goal, the current study extends our platform of nonmyeloablative, partially HLA-mismatched bone marrow transplant (BMT) and Peripheral Blood Stem Cell Transplant (PBSCT) to the use of such donors, investigating up to several postgrafting immunosuppression regimens that incorporate high-dose Cy. Of central interest is the incorporation of sirolimus into this postgrafting immunosuppression regimen.
The primary goal for phase 1 is to identify a transplant regimen associated with acceptable rates of severe acute GVHD and NRM by Day 100 and for phase 2 estimate the 6-month probability of survival without having had acute grade III- IV GVHD or graft failure.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patient Inclusion Criteria:
- •Patient age 0.5-75 years
- •Absence of a suitable related or unrelated bone marrow donor who is molecularly matched at HLA-A, B, Cw, DRB1, and DQB
- •Absence of a suitable partially HLA-mismatched (haploidentical), first-degree related donor. Donors who are homozygous for the CCR5delta32 polymorphism are given preference.
- •Eligible diagnoses:
- •Relapsed or refractory acute leukemia in second or subsequent remission, with remission defined as <5% bone marrow blasts morphologically
- •Poor-risk acute leukemia in first remission, with remission defined as <5% bone marrow blasts morphologically:
- •AML with at least one of the following:
- •AML arising from MDS or a myeloproliferative disorder, or secondary AML
- •Presence of Flt3 internal tandem duplications
- •Poor-risk cytogenetics: Complex karyotype [> 3 abnormalities], inv(3), t(3;3), t(6;9), MLL rearrangement with the exception of t(9;11), or abnormalities of chromosome 5 or 7
- •Primary refractory disease
- •ALL (leukemia and/or lymphoma) with at least one of the following:
- •Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), or MLL rearrangement
- •Clear evidence of hypodiploidy
- •Primary refractory disease
- •Biphenotypic leukemia
- •MDS with at least one of the following poor-risk features:
- •Poor-risk cytogenetics (7/7q minus or complex cytogenetics)
- •IPSS score of INT-2 or greater
- •Treatment-related MDS
- •MDS diagnosed before age 21 years
- •Progression on or lack of response to standard DNA-methyltransferase inhibitor therapy
- •Life-threatening cytopenias, including those generally requiring greater than weekly transfusions
- •Interferon- or imatinib-refractory CML in first chronic phase, or non-blast crisis CML beyond first chronic phase.
- •Philadelphia chromosome negative myeloproliferative disease.
- •Chronic myelomonocytic leukemia.
- •Juvenile myelomonocytic leukemia.
- •Low-grade non-Hodgkin lymphoma (including SLL and CLL) or plasma cell neoplasm that has:
- •progressed after at least two prior therapies (excluding single agent rituximab and single agent steroids), or
- •in the case of lymphoma undergone histologic conversion;
- •patients with transformed lymphomas must have stable disease or better.
- •Poor-risk CLL or SLL as follows:
- •11q deletion disease that has progressed after a combination chemotherapy regimen,
- •17p deletion disease,
- •or histologic conversion;
- •patients with transformed lymphomas must have stable disease or better.
- •Aggressive non-Hodgkin lymphoma as follows, provided there is stable disease or better to last therapy:
- •NK or NK-T cell lymphoma, hepatosplenic T-cell lymphoma, or subcutaneous panniculitic T-cell lymphoma, blastic/ blastoid variant of mantle cell lymphoma
- •Hodgkin or aggressive non Hodgkin lymphoma that has failed at least one multiagent regimen, and the patient is either ineligible for autologous BMT or autologous BMT is not recommended.
- •Eligible subtypes of aggressive non-Hodgkin lymphoma include:
- •mantle cell lymphoma
- •follicular grade 3 lymphoma
- •diffuse large B-cell lymphoma or its subtypes, excluding primary CNS lymphoma
- •primary mediastinal large B-cell lymphoma
- •large B-cell lymphoma, unspecified
- •anaplastic large cell lymphoma, excluding skin-only disease
- •Burkitt's lymphoma or atypical Burkitt's lymphoma (high-grade B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's), in complete remission
- •Patients with CLL, SLL, or prolymphocytic leukemia must have < 20% bone marrow involvement by malignancy (to lower risk of graft rejection).
- •One of the following, in order to lower risk of graft rejection:
- 另有 9 项未显示
排除标准
- •Not pregnant or breast-feeding.
- •No uncontrolled bacterial, viral, or fungal infection.
- •Note: HIV-infected patients are potentially eligible. Eligibility of HIV-infected patients will be determined on a case-by-case basis.
- •No previous allogeneic BMT (syngeneic BMT permissible).
- •Active extramedullary leukemia or known active CNS involvement by malignancy. Such disease treated into remission is permitted.
- •Donor Inclusion Criteria:
- •Potential donors consist of:
- •Unrelated donors
- •Second-degree relatives
- •First cousins
- •The donor and recipient must be identical at at least 5 HLA alleles based on high resolution typing of HLA-A, -B, -Cw, -DRB1, and -DQB1, with at least one allele matched for a HLA class I gene (HLA-A, -B, or -Cw) and at least one allele matched for a class II gene (HLA-DRB1 or -DQB1).
- •Meets institutional selection criteria and medically fit to donate. 4 . Lack of recipient anti-donor HLA antibody. Note: In some instances, low level, non-cytotoxic HLA specific antibodies may be permissible if they are found to be at a level well below that detectable by flow cytometry. This will be decided on a case-by-case basis by the PI and one of the immunogenetics directors. Pheresis to reduce anti-HLA antibodies is permissible; however eligibility to proceed with the transplant regimen would be contingent upon the result.
- •Donor Exclusion Criteria:
- •Donor must not be HLA identical to the recipient.
- •Has not donated blood products to recipient.
研究组 & 干预措施
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Fludarabine (Drug)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Cytoxan (Drug)
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Cytoxan (Drug)
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Total Body Irradiation (Radiation)
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Allogeneic Blood or Marrow Transplant (Procedure)
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Mycophenolate Mofetil (Drug)
REGIMEN B
Active Comparator
Pre-BMT :
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy total body irradiation (TBI) administered in a single fraction
Day 0: Allogeneic blood or marrow transplantation (BMT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: Mycophenolate Mofetil (MMF) 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Sirolimus (Drug)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Fludarabine (Drug)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Total Body Irradiation (Radiation)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Allogeneic Blood or Marrow Transplant (Procedure)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Mycophenolate Mofetil (Drug)
REGIMEN C
Active Comparator
Pre-BMT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: BMT
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 5 thru Day 180: Tacrolimus 1 mg administered IV QD
干预措施: Tacrolimus (Drug)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Fludarabine (Drug)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Cytoxan (Drug)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Total Body Irradiation (Radiation)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Peripheral Blood Stem Cell Transplant (Procedure)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Mycophenolate Mofetil (Drug)
REGIMEN B2
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Sirolimus (Drug)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Fludarabine (Drug)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Cytoxan (Drug)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Total Body Irradiation (Radiation)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Peripheral Blood Stem Cell Transplant (Procedure)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Mycophenolate Mofetil (Drug)
REGIMEN B3: HIV patients with CCRd32 homozygous donors
Active Comparator
Pre-PBSCT:
- Day -6 through -2: Fludarabine 30 mg/m2/day (adjusted for renal function; maximum cumulative dose, 150 mg/m2) administered IV
- Day -6 and -5: Cytoxan 14.5 mg/kg/day administered IV
- Day -1: 400 cGy TBI administered in a single fraction
Day 0: Peripheral Blood Stem Cell Transplant (PBSCT)
Post-Transplantation Immunosuppression Consisting of:
- Day 3 and 4: High-dose Cytoxan 50mg/kg/day (adjusted according to IBW) administered IV
- Day 5: Sirolimus loading dose 6 mg PO once
- Day 5 thru Day 35: MMF 15 mg/kg PO TID (maximum daily dose 3 g/day)
- Day 6 thru Day 180: Sirolimus maintenance dose 2 mg PO QD with dose adjustments to maintain trough of 3 - 12 ng/mL
干预措施: Sirolimus (Drug)
结局指标
主要结局
Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD)
时间窗: Study Day 100
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable rates of severe acute GVHD (\< 25%).
Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM)
时间窗: Study Day 100
Two immunosuppressive regimens with Fludarabine-Cytoxan-TBI conditioning will be studied in reduced-intensity, partially HLA mismatched allogeneic BMT from unrelated or non-first-degree related donors. Transplant regimen will be determined by acceptable number of participants with transplant-related NRM.
6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure.
时间窗: 6 months
Number of participants who do not have grade II-IV GVHD or evidence of graft failure will be assessed.
次要结局
- Progression-free Survival(2 years)
- Event-free Survival(7 years)
- Overall Survival(7 years)
- Cumulative Incidence of Progression or Relapse(7 years)
- Cumulative Incidence of Non-relapse Mortality (NRM).(7 years)
- Cumulative Incidence of Acute Grade II-IV GVHD.(1 year)
- Cumulative Incidence of Acute Grade III-IV GVHD(1 year)
- Cumulative Incidence of Chronic GVHD(1 year)
- Cumulative Incidence of Graft Failure(1 year)
- Cumulative Incidence of Neutrophil Recovery(1 year)
- Cumulative Incidence of Platelet Recovery(1 year)
- Cumulative Incidence of Donor Engraftment(1 year)
- Cumulative Incidence of Failure Free Survival(7 years)
研究者
研究点 (1)
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