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| ID | Type | Description | Link |
|---|---|---|---|
| NCI-2014-01301 | Registry Identifier | CTRP (Clinical Trial Reporting Program) | |
| 2684.00 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| R01HL121568 | U.S. NIH Grant/Contract | View source | |
| RG9214012 | Other Identifier | Fred Hutch/University of Washington Cancer Consortium | |
| 2P01CA018029 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.
OUTLINE: Patients are assigned to 1 of 4 treatment arms.
CONDITIONING:
ARMS A AND C (high-intensity myeloablative conditioning): Patients undergo total body irradiation twice daily (BID) on days -10 to -7. Patients also receive thiotepa intravenously (IV) over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
ARMS B AND D (lower-intensity myeloablative conditioning): Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation once daily (QD) on days -2 and -1.
TRANSPLANT: In all arms, patients undergo allogeneic HSCT with granulocyte colony-stimulating factor (GCSF)-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0.
GVHD PROPHYLAXIS:
ARMS A AND C: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or orally (PO) (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
ARMS B AND D: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on days -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the principal investigator.
After completion of study treatment, patients are followed up at 80-100 days, 360 days, and then yearly for up to 5 years.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A (MRD) | Experimental | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
|
| Arm B (MRD) | Experimental | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplantation | Procedure | Undergo allogeneic HSCT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Chronic GVHD | Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression. | Up to 5 years post-transplant |
| Time to Completion of Prednisone | Measure the number of days to discontinuation of prednisone in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome) | Up to 5 years post-transplant |
| Time to Completion of All Immunosuppression | Measure the number of days to discontinuation of all immunosuppression in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome) | Up to 5 years post-transplant |
| Requirement of Immunosuppression at 2 Years After Transplant | Number of patients requiring immunosuppression 2 years after transplant. | At 2 years post transplant |
| Acute GVHD | Presence of acute graft-versus-host disease (GVHD) grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver, in patients who received Naive t cell depleted PBSCT. Staging and grading are found on page 8 of the JCO supplement (Bleakley et al., 2022, original references Glucksberg et all, 1974, Przepiorka et all, 1995 ) with higher grade indicating worse outcomes. | Through day 100 post-transplant |
| Graft Failure |
| Measure | Description | Time Frame |
|---|---|---|
| Transplant Related Mortality by Day 100 | Defined as mortality in any patient for whom there has not been a diagnosis of relapse. | Through day 100 post-transplant |
| Relapse | Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology. |
| Measure | Description | Time Frame |
|---|---|---|
| Other Immunosuppressive Agents | Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) | Up to 5 years |
| aGVHD Management - Secondary | Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management |
Inclusion Criteria:
Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation and have one of the following diagnoses:
Patients 0-49 years old will be enrolled in Arm A or C (high-intensity)
Patients 50-60 years old will be enrolled in Arm B or D (lower intensity); patients eligible for Arms B or D also include those who have received previous allogeneic HCT, or who have co-morbid conditions rendering them unsuitable for high-dose conditioning, determined in consultation with the principal investigator
Patient with a HLA-matched (HLA-A, B, C, and DR beta 1 [DRB1] molecularly matched) unrelated donor or related donor capable of donating PBSC
DONOR INCLUSION:
HLA-matched related donors >= 18 years and capable and willing to donate PBSC (Arms A and B)
HLA-matched unrelated donors (HLA-A, B, C, and DRB1 matched based on high-resolution typing) capable and willing to donate PBSC (Arms C and D)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marie Bleakley | Fred Hutch/University of Washington Cancer Consortium | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | 15232 | United States | ||
| Fred Hutch/University of Washington Cancer Consortium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35007144 | Result | Bleakley M, Sehgal A, Seropian S, Biernacki MA, Krakow EF, Dahlberg A, Persinger H, Hilzinger B, Martin PJ, Carpenter PA, Flowers ME, Voutsinas J, Gooley TA, Loeb K, Wood BL, Heimfeld S, Riddell SR, Shlomchik WD. Naive T-Cell Depletion to Prevent Chronic Graft-Versus-Host Disease. J Clin Oncol. 2022 Apr 10;40(11):1174-1185. doi: 10.1200/JCO.21.01755. Epub 2022 Jan 10. |
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Of the 84 enrolled participants, only 77 received naïve T-cell deplete grafts. 6 out of the 7 remaining participants received unmanipulated grafts, 5 because cell selection precluded inadequate donor CD34 cells, and 1 because cell selection was unsuccessful. The seventh participant switched to cord blood transplant because the donor became medically unavailable after the patient had begun conditioning. Characteristics and outcomes of these patients are in table S2 and S10 of JCO paper.
Participants were recruited based on referral for Hematopoietic Cell Transplant at Fred Hutchinson Cancer Center and University of Pittsburgh Medical Center between July 2014 and March 2020. The first participant enrolled on March 23, 2015 and the last participant enrolled on March 11, 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A (MRD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| 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 | Aug 2, 2019 |
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| Arm C (MUD) | Experimental | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
|
| Arm D (MUD) | Experimental | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| Cyclophosphamide | Drug | Given IV |
|
|
| Fludarabine Phosphate | Drug | Given IV |
|
|
| Laboratory Biomarker Analysis | Other | Correlative studies |
|
| Methotrexate | Drug | Given IV |
|
|
| Mycophenolate Mofetil | Drug | Given IV and PO |
|
|
| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC |
|
|
| Peripheral Blood Stem Cell Transplantation | Procedure | Undergo PBSCT with CD45RA-depleted cells |
|
|
| Tacrolimus | Drug | Given IV or PO |
|
|
| Thiotepa | Drug | Given IV |
|
|
| Total-Body Irradiation | Radiation | Undergo TBI |
|
|
Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft. |
| Up to 5 years post-transplant |
| Up to 5 years post-transplant |
| Up to day 100 |
| Engraftment - ANC >500/uL | Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days | Through day 100 post-transplant |
| Engraftment - ANC <1,000/uL | Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results | through Day 100 post-transplant |
| Platelet Engraftment | Time to platelet count > 20,000/uL for 3 days without transfusion | Through day 100 post-transplant |
| Platelet Engraftment - 50,000/uL | Time to platelet count > 50,000/uL for 3 days without transfusion | Through day 100 post-transplant |
| Chimerism Analysis | Will be analyzed from peripheral blood or marrow. | Up to 360 days |
| Seattle |
| Washington |
| 98109 |
| United States |
| FG001 | Arm B (MRD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
| FG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| FG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
| Alive at Day 28 post transplant |
|
| Alive at Day 100 post transplant |
|
| Alive at 1 year post transplant |
|
| Alive at 2 years post transplant |
|
| Alive at 3 years post transplant |
|
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A (MRD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| BG001 | Arm B (MRD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
| BG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| BG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Chronic GVHD | Occurrence of chronic graft-versus-host disease (GHVD), defined operationally as the occurrence of compatible symptoms meeting National Institutes of Health criteria and requiring systemic pharmacological immunosuppression. | Participants who received Naive T cell depleted PBSCT and were alive at Day 100 post-transplant were analyzed. | Posted | Count of Participants | Participants | Up to 5 years post-transplant |
|
|
| |||||||||||||||||||||||||||||||||||
| Other Pre-specified | Other Immunosuppressive Agents | Use of additional immune suppressive agents other than first line therapy (prednisone and tacrolimus/cyclosporine) | Not Posted | Up to 5 years | Participants | ||||||||||||||||||||||||||||||||||||||||
| Primary | Time to Completion of Prednisone | Measure the number of days to discontinuation of prednisone in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome) | Participants who received NTCD PBSC transplant and were alive at day 28 post-transplant | Posted | Median | Standard Deviation | Days post transplant | Up to 5 years post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Primary | Time to Completion of All Immunosuppression | Measure the number of days to discontinuation of all immunosuppression in recipients of CD45RA+ T cell-depleted PBSCT by arm. Possible outcomes range from no systemic immunosuppression (best outcome) to 5 years on immunosuppression (poor outcome) | Participants who received NTCD PBSC transplant and were alive at day 28 post-transplant | Posted | Median | Standard Deviation | Days | Up to 5 years post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Primary | Requirement of Immunosuppression at 2 Years After Transplant | Number of patients requiring immunosuppression 2 years after transplant. | Participants who received NTCD PBSC and were alive at 2 years | Posted | Count of Participants | Participants | At 2 years post transplant |
| |||||||||||||||||||||||||||||||||||||
| Primary | Acute GVHD | Presence of acute graft-versus-host disease (GVHD) grades II-IV, defined operationally as the occurrence of compatible symptoms or signs in the skin, gastrointestinal tract, or liver, in patients who received Naive t cell depleted PBSCT. Staging and grading are found on page 8 of the JCO supplement (Bleakley et al., 2022, original references Glucksberg et all, 1974, Przepiorka et all, 1995 ) with higher grade indicating worse outcomes. | Participants who received Naive T Cell Depleted PBSC and were alive at day 100 post-transplant | Posted | Count of Participants | Participants | Through day 100 post-transplant |
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | aGVHD Management - Secondary | Requirement for secondary systemic therapy for acute graft-versus-host disease (GVHD) management | Not Posted | Up to day 100 | Participants | ||||||||||||||||||||||||||||||||||||||||
| Primary | Graft Failure | Defined operationally as failure to reach an absolute neutrophil count (ANC) of > 500/ul for 3 consecutive days by day 28 or irreversible decrease in ANC to < 100 after an established donor graft. | Participants who received a Naive T Cell depleted PBSCT and who were alive at day 28 post-transplant | Posted | Count of Participants | Participants | Up to 5 years post-transplant |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Transplant Related Mortality by Day 100 | Defined as mortality in any patient for whom there has not been a diagnosis of relapse. | All participants who received a NTCD PBSC transplant | Posted | Count of Participants | Participants | Through day 100 post-transplant |
| |||||||||||||||||||||||||||||||||||||
| Secondary | Relapse | Defined by the presence of malignant cells in marrow, peripheral blood, or extramedullary sites by histopathology. | All participants who received a Naive T cell deplete transplant | Posted | Count of Participants | Participants | Up to 5 years post-transplant |
| |||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Engraftment - ANC >500/uL | Time to absolute neutrophil count (ANC) of > 500/uL on the first of three consecutive days | Participants who received NTCD PBSC and were alive at day 28 post-transplant | Posted | Median | Standard Deviation | Days | Through day 100 post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Engraftment - ANC <1,000/uL | Time to absolute neutrophil count (ANC) of > 1,000/uL on the first of three consecutive test results | Participants who received NTCD PBSC transplant and were alive at day 28 post-transplant | Posted | Median | Standard Deviation | Days | through Day 100 post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Platelet Engraftment | Time to platelet count > 20,000/uL for 3 days without transfusion | Participants who received NTCD PBSC and were alive at Day 100 post-transplant | Posted | Median | Standard Deviation | Days post transplant | Through day 100 post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Platelet Engraftment - 50,000/uL | Time to platelet count > 50,000/uL for 3 days without transfusion | Participants who received NTCD PBSC and were alive at Day 100 post-transplant | Posted | Median | Standard Deviation | Days post transplant | Through day 100 post-transplant |
| ||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Chimerism Analysis | Will be analyzed from peripheral blood or marrow. | Not Posted | Up to 360 days | Participants |
Serious and other adverse events were reported from pre-transplant conditioning through day 100 post-transplant. All-cause mortality (including both relapse and non-relapse mortality) was assessed for up to 5 years post-transplant.
Only grades 3-5 non-hematologic adverse events were captured.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A (MRD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. | 5 | 21 | 21 | 21 | 6 | 21 |
| EG001 | Arm B (MRD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with GCSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. | 4 | 20 | 17 | 20 | 8 | 20 |
| EG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. | 4 | 18 | 18 | 18 | 6 | 18 |
| EG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. | 4 | 18 | 15 | 18 | 8 | 18 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Heart Failure | Cardiac disorders | CTCAE v4 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Esophagitis | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Gastrointestinal Pain | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Gastroparesis | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Mucositis oral | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Typhlitis | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Fever | General disorders | CTCAE v4 | Systematic Assessment |
| |
| Pain | General disorders | CTCAE v4 | Systematic Assessment |
| |
| Hepatic Failure | Hepatobiliary disorders | CTCAE v4 | Systematic Assessment |
| |
| Anorectal infection | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Catheter related infection | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Enterocolitis | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Infections and infestations - Other | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Lung Infection | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Otitis Media | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Soft Tissue Infection | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | CTCAE v4 | Systematic Assessment |
| |
| Vascular access complication | Injury, poisoning and procedural complications | CTCAE v4 | Systematic Assessment |
| |
| Weight loss investigations | Investigations | CTCAE v4 | Systematic Assessment |
| |
| Anorexia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | CTCAE v4 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE v4 | Systematic Assessment |
| |
| Arachnoiditis | Nervous system disorders | CTCAE v4 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | CTCAE v4 | Systematic Assessment |
| |
| Headache | Nervous system disorders | CTCAE v4 | Systematic Assessment |
| |
| Intracranial hemorrhage | Nervous system disorders | CTCAE v4 | Systematic Assessment |
| |
| Mania | Psychiatric disorders | CTCAE v4 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | CTCAE v4 | Systematic Assessment |
| |
| Aspiration | Respiratory, thoracic and mediastinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Pulmonary edema | Respiratory, thoracic and mediastinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Rash, maculo-papular | Skin and subcutaneous tissue disorders | CTCAE v4 | Systematic Assessment |
| |
| Capillary leak syndrome | Vascular disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | CTCAE v4 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | CTCAE v4 | Systematic Assessment |
| |
| Cytokine release syndrome | Immune system disorders | CTCAE v4 | Systematic Assessment |
| |
| Infections and infestations, other | Infections and infestations | CTCAE v4 | Systematic Assessment |
| |
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypermagnesemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypokalemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hyponatremia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE v4 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | CTCAE v4 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE v4 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE v4 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marie Bleakley, MD, PhD | Fred Hutch Cancer Center | 206-667-6572 | mbleakle@fredhutch.org |
| Mar 12, 2026 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D015465 | Leukemia, Myeloid, Accelerated Phase |
| D015456 | Leukemia, Biphenotypic, Acute |
| D001752 | Blast Crisis |
| D000099067 | Blastic Plasmacytoid Dendritic Cell Neoplasm |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D000754 | Anemia, Refractory, with Excess of Blasts |
| D015470 | Leukemia, Myeloid, Acute |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D007945 | Leukemia, Lymphoid |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002471 | Cell Transformation, Neoplastic |
| D063646 | Carcinogenesis |
| D009385 | Neoplastic Processes |
| D015620 | Histiocytic Disorders, Malignant |
| D008223 | Lymphoma |
| D019337 | Hematologic Neoplasms |
| D009371 | Neoplasms by Site |
| D012878 | Skin Neoplasms |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D000753 | Anemia, Refractory |
| D000740 | Anemia |
| D009190 | Myelodysplastic Syndromes |
Not provided
Not provided
| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C042382 | fludarabine phosphate |
| D008727 | Methotrexate |
| C015342 | merphos |
| D009173 | Mycophenolic Acid |
| D036102 | Peripheral Blood Stem Cell Transplantation |
| D016559 | Tacrolimus |
| D013852 | Thiotepa |
| D014916 | Whole-Body Irradiation |
| 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 |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D002208 | Caproates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D018380 | Hematopoietic Stem Cell Transplantation |
| D033581 | Stem Cell Transplantation |
| D017690 | Cell Transplantation |
| D064987 | Cell- and Tissue-Based Therapy |
| D001691 | Biological Therapy |
| D013812 | Therapeutics |
| D014180 | Transplantation |
| D013514 | Surgical Procedures, Operative |
| D018942 | Macrolides |
| D007783 | Lactones |
| D013721 | Triethylenephosphoramide |
| D001388 | Aziridines |
| D001389 | Azirines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D011878 | Radiotherapy |
| D008919 | Investigative Techniques |
Not provided
Not provided
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Mild Chronic GVHD not requiring systemic corticosteroids |
|
| Mild Chronic GVHD requiring systemic corticosteroids |
|
| Moderate Chronic GVHD (requiring systemic corticosteroids) |
|
| Severe Chronic GVHD (requiring systemic corticosteroids) |
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
|
|
| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
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| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
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| OG002 | Arm C (MUD / High Intensity Conditioning) | HIGH-INTENSITY MYELOABLATIVE CONDITIONING: Patients undergo total body irradiation BID on days -10 to -7. Patients also receive thiotepa IV over 4 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days with taper in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11. |
| OG003 | Arm D (MUD / Low Intensity Conditioning) | LOWER-INTENSITY MYELOABLATIVE CONDITIONING: Patients receive cyclophosphamide IV over 1 hour on day -6, fludarabine phosphate IV over 30 minutes on days -6 to -2, and thiotepa IV over 4 hours on days -5 and -4. Patients also undergo total body irradiation QD on days -2 and -1. TRANSPLANT: In all arms, patients undergo allogeneic HSCT with G-CSF-mobilized CD34-enriched PBSC and CD45RA-depleted cells on day 0. GVHD PROPHYLAXIS: Beginning day -1, patients receive tacrolimus IV over 22-24 hours or PO (BID if given PO) for 50 days and mycophenolate mofetil IV and PO every 8 hours on day -3 to approximately day 30, with or without taper at the discretion of the treating physician. Mycophenolate mofetil should be continued or resumed after day 30 if donor chimerism is low, after discussion with the Principal Investigator. |
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