Reduced Intensity, Partially HLA Mismatched BMT to Treat... | NCT01203722

ID	Type	Description	Link
NA_00039823	Other Identifier	JHM IRB
P01CA015396	U.S. NIH Grant/Contract		View source

Name	Class
National Cancer Institute (NCI)	NIH

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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	Drug: Fludarabine Drug: Cytoxan Radiation: Total Body Irradiation Procedure: Allogeneic Blood or Marrow Transplant Drug: Mycophenolate Mofetil Drug: Sirolimus
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	Drug: Fludarabine Drug: Cytoxan Radiation: Total Body Irradiation Procedure: Allogeneic Blood or Marrow Transplant Drug: Mycophenolate Mofetil Drug: Tacrolimus
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

Name	Type	Description	Arm Group Labels	Other Names
Fludarabine	Drug	Fludarabine 30 mg/m2/day	REGIMEN B REGIMEN B2 REGIMEN B3: HIV patients with CCRd32 homozygous donors REGIMEN C

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD)	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%).	Study Day 100
Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM)	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.	Study Day 100
6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure.	Number of participants who do not have grade II-IV GVHD or evidence of graft failure will be assessed.	6 months

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival	All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.	2 years

Eligibility Module

Eligibility Criteria

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 DQB1.
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:
1. Relapsed or refractory acute leukemia in second or subsequent remission, with remission defined as <5% bone marrow blasts morphologically
2. 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
3. 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
4. Interferon- or imatinib-refractory CML in first chronic phase, or non-blast crisis CML beyond first chronic phase.
5. Philadelphia chromosome negative myeloproliferative disease.
6. Chronic myelomonocytic leukemia.
7. Juvenile myelomonocytic leukemia.
8. 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.
9. 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.
10. 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:
- Cytotoxic chemotherapy, an adequate course of 5-azacitidine or decitabine, or alemtuzumab within 3 months prior to start of conditioning; or
- Previous BMT within 6 months prior to start of conditioning.
NOTE: Patients who have received treatment outside of these windows may be eligible if it is deemed sufficient to reduce graft rejection risk; this will be decided on a case-by-case basis by the PI or co-PI.
Any previous BMT must have occurred at least 3 months prior to start of conditioning.
Adequate end-organ function as measured by:
1. Left ventricular ejection fraction greater than or equal to 35%, or shortening fraction > 25%, unless cleared by a cardiologist
2. Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST < 5 x ULN
3. FEV1 and FVC > 40% of predicted; or in pediatric patients, if unable to perform pulmonary function tests due to young age, oxygen saturation >92% on room air
ECOG performance status < 2 or Karnofsky or Lansky score > 60

Patient Exclusion Criteria:

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.

Name	Affiliation	Role
Richard Ambinder, MD	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins		Baltimore	Maryland	21231-2410	United States

PubMed Identifier	Type	Citation	Retractions
34425261	Derived	Rappazzo KC, Zahurak M, Bettinotti M, Ali SA, Ambinder AJ, Bolanos-Meade J, Borrello I, Dezern AE, Gladstone D, Gocke C, Fuchs E, Huff CA, Imus PH, Jain T, Luznik L, Rahmat L, Swinnen LJ, Wagner-Johnston N, Jones RJ, Ambinder RF. Nonmyeloablative, HLA-Mismatched Unrelated Peripheral Blood Transplantation with High-Dose Post-Transplantation Cyclophosphamide. Transplant Cell Ther. 2021 Nov;27(11):909.e1-909.e6. doi: 10.1016/j.jtct.2021.08.013. Epub 2021 Aug 20.
29242852

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Nov 4, 2020

Arm/Group Information

ID	Title	Description
BG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
BG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily
BG002	REGIMEN B2	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
BG003	REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00054 BG0011 BG00230 BG0032 BG00487

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Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Have Severe Acute Graft-versus-host-disease (GVHD)

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%).

aGVHD data collected for 21 of the 54 participants enrolled in Regimen B.

Posted

Count of Participants

Participants

Study Day 100

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily
OG002	REGIMEN B2	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG003	REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily

Units	Counts
Participants	OG00021 OG0011 OG00230 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002 OG0010 OG0025 OG003

Primary

Number of Participants Who Have Transplant-related Nonrelapse Mortality (NRM)

Posted

Count of Participants

Participants

Study Day 100

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001

Primary

6-month Probability of Survival as Assessed by Absence of Grade III-IV GVHD or Evidence of Graft Failure.

Number of participants who do not have grade II-IV GVHD or evidence of graft failure will be assessed.

Posted

Count of Participants

Participants

6 months

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily

Secondary

Progression-free Survival

All patients will be tracked from Day 0 to date of first objective disease progression, death from any cause, or last patient evaluation. Patients who have not progressed or died will be censored at the last date they were assessed and deemed free of relapse or progression.

Posted

Count of Participants

Participants

2 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C

Secondary

Event-free Survival

All patients will be tracked from Day 0 to date of first observed disease progression, or death from any cause, or last patient evaluation. Patients will be followed on study to identify instances of death, progression or disease recurrence.

Posted

Count of Participants

Participants

7 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C

Secondary

Overall Survival

Posted

Count of Participants

Participants

7 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C

Secondary

Cumulative Incidence of Progression or Relapse

Posted

Count of Participants

Participants

7 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C

Secondary

Cumulative Incidence of Non-relapse Mortality (NRM).

All patients will be tracked from Day 0 to date of first observed disease relapse or progression, or death from disease, or last patient evaluation. Patients who have not progressed or died by their last patient contact visit will be censored at the last date they were assessed and deemed free of relapse or progression.

Posted

Count of Participants

Participants

7 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001

Secondary

Cumulative Incidence of Acute Grade II-IV GVHD.

All suspected cases of acute GVHD must be confirmed histologically by biopsy of an affected organ (skin, liver, or gastrointestinal tract). Date of symptom onset, date of biopsy confirmation of GVHD, maximum clinical grade, and dates and types of treatment will be recorded. Dates of symptom onset of grade II or higher GVHD and grade III-IV GVHD will be recorded.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001

Secondary

Cumulative Incidence of Acute Grade III-IV GVHD

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001

Secondary

Cumulative Incidence of Chronic GVHD

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001

Secondary

Cumulative Incidence of Graft Failure

Number of cases with less than 5% donor chimerism in blood and/or bone marrow on ~Day 30 or after and on all subsequent measurements, in the absence of documented bone marrow involvement by malignancy.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily

Secondary

Cumulative Incidence of Neutrophil Recovery

Number of cases who achieve a post nadir ANC greater or equal to 500/mm3 for three consecutive measurements on different days.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily

Secondary

Cumulative Incidence of Platelet Recovery

Number of cases who achieve a platelet count greater than 20,000/mm3 or greater than 50,000/mm3 with no platelet transfusions in the preceding seven days, as measured as maintained on at least three consecutive measurements on different days.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C

Secondary

Cumulative Incidence of Donor Engraftment

Number of cases who achieve either mixed donor chimerism is defined as greater than 5%, but less than 95%, donor or full donor chimerism is defined as > 95% donor.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily

Secondary

Cumulative Incidence of Failure Free Survival

Number of cases who reach the end of the trial without severe acute (grade III-IV) GVHD, graft failure, or non-relapse mortality

Posted

Count of Participants

Participants

7 years

ID	Title	Description
OG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily
OG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	REGIMEN B	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily	2	54	1	54	1	54
EG001	REGIMEN C	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Allogeneic Blood or Marrow Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Tacrolimus: Tacrolimus 1mg intravenously, daily	0	1	0	1	0	1
EG002	REGIMEN B2	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily	1	30	0	30	0	30
EG003	REGIMEN B3: HIV Patients With CCRd32 Homozygous Donors	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 Fludarabine: Fludarabine 30 mg/m2/day Cytoxan: Pre-BMT: Cytoxan 14.5 mg/kg/day administered IV; Post-Transplantation: High-dose Cytoxan 50mg/kg/day Total Body Irradiation: 400 cGy TBI administered in a single fraction Peripheral Blood Stem Cell Transplant Mycophenolate Mofetil: 15mg/kg by mouth three times daily Sirolimus: Loading Dose: Sirolimus 6mg by mouth once; Maintenance dose: Sirolimus 2mg by mouth daily	0	2	0	2	0	2

ID	Term
D019337	Hematologic Neoplasms
D000754	Anemia, Refractory, with Excess of Blasts
D008223	Lymphoma

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D000753	Anemia, Refractory
D000740	Anemia
D009190	Myelodysplastic Syndromes
D001855	Bone Marrow Diseases
D009370	Neoplasms by Histologic Type
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
C024352	fludarabine
D003520	Cyclophosphamide
D014916	Whole-Body Irradiation
D036102	Peripheral Blood Stem Cell Transplantation
D009173	Mycophenolic Acid
D020123	Sirolimus
D016559	Tacrolimus

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D011878	Radiotherapy
D013812	Therapeutics
D008919	Investigative Techniques
D018380	Hematopoietic Stem Cell Transplantation
D033581	Stem Cell Transplantation
D017690	Cell Transplantation
D064987	Cell- and Tissue-Based Therapy
D001691	Biological Therapy
D014180	Transplantation
D013514	Surgical Procedures, Operative
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005227	Fatty Acids
D008055	Lipids
D018942	Macrolides
D007783	Lactones