Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML
Sponsor
Stanford University (Other)
Overall Status
Terminated
CT.gov ID
NCT00568633
Collaborator
Genzyme, a Sanofi Company (Industry)
58
5
2
101
11.6
0.1
Study Details
Study Description
Brief Summary
Acute myeloid leukemia (AML) is a cancer of the bone marrow that mostly affects older adults. Even with the best chemotherapy, two-year disease-free survival is achieved in a minority of patients. Bone marrow transplantation from a sibling donor may improve cure rates; however, patients over 50 years of age have a high risk of complications and therefore generally are excluded from this treatment option. Recently our group developed a transplantation strategy for older cancer patients that protects against transplant-associated complications, yet does not interfere with the ability of the transplanted donor cells to destroy cancer cells. With this new method, we can now safely evaluate transplantation as a curative therapy for AML patients over the age of 50. We have assembled clinical and scientific researchers throughout the state of California to study and compare bone marrow transplantation using our new approach with the best standard of care chemotherapy in AML patients over the age of 50. The results of this study have the potential to establish a new treatment standard that will improve survival of older AML patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
58 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Treatment assignment was based on availability of an HLA-matched donor.Treatment assignment was based on availability of an HLA-matched donor.
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A California Cooperative Clinical Study Comparing Allogeneic Hematopoietic Cell Transplantation Using Nonmyeloablative Host Conditioning With Total Lymphoid Irradiation and Anti-thymocyte Globulin Versus Best Standard of Care in Acute Myeloid Leukemia (AML) in First Complete Remission
Actual Study Start Date
:
Aug 1, 2007
Actual Primary Completion Date
:
Dec 31, 2015
Actual Study Completion Date
:
Dec 31, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Allo-HSCT + TLI + ATG Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 |
Procedure: Allogeneic HSCT
Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg.
Other Names:
Drug: Anti-thymocyte globulin (ATG)
1.5 mg/kg for 5 days by IV
Other Names:
Drug: Cyclosporine (CSP)
6.25 mg/kg twice daily oral
Other Names:
Drug: Mycophenolate mofetil (MMF)
15 mg/kg twice daily oral
Other Names:
Radiation: Total lymphoid irradiation (TLI)
80 cGy/fraction radiotherapy in 10 fractions.
Drug: Methylprednisolone sodium succinate
1.0 mg/kg for 5 days by IV
Other Names:
|
| Active Comparator: Best Standard Care Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
Drug: Best standard care
Intervention consist of:
Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation)
Autologous transplantation
Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning
Umbilical cord blood transplantation
Haploidentical transplantation
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [2 years]
Overall survival defined as the time interval between the date of attaining a first complete remission (CR) and the date of death from any cause. The outcome is reported as the number of participants alive (without dispersion).
Secondary Outcome Measures
- Disease-free Survival (DFS) [2 years]
Disease-free survival is defined as the time interval between the date of attaining a first complete remission (CR) and the date of relapse. Disease free survival (DFS) will compared to conventional therapy vs Non-myeloablative Host Conditioning (NMA HCT). The outcome is reported as the number of participants which never experienced disease relapse (without dispersion).
- Non-relapse Mortality [2 years]
Non-relapse mortality is defined as death that occurs after therapy, from any cause except a cause associated with relapse. This will be reported as the number of participants experiencing non-relapse mortality (a number without dispersion).
- Relapse Rate [2 years]
Relapse will be determined as ≥ 5% blast cells in the bone marrow, not secondary to regeneration after myelosuppressive therapy; OR emergence of extramedullary leukemia; OR the re-emergence of blasts in the peripheral blood. The outcome will be reported as the number and percentage of participants that meet these criteria (a number without dispersion).
- Transplant-related Mortality [100 days and 6 months]
Transplant-related mortality will be assessed as any death occurring within 6 months post-transplant, from any cause except relapse. It will be measured at 100 day and 6 months after transplant. The outcome is expressed as at the number of participants experiencing transplant-related mortality (a number without dispersion).
- Complete Donor Hematopoietic Cell Chimerism [2 years]
Complete donor hematopoietic cell chimerism was evaluated in transplant recipients. Complete donor chimerism will be assessed as the presence of > 95% donor T-cells (CD3+) in the blood. The outcome is reported as the percentage of participants that achieve complete donor chimerism, a number without dispersion.
- Early Graft Loss [2 years]
Early graft loss means a failure to achieve donor T-cell chimerism of > 5% at any time after transplant. The outcome is reported as the percentage of participants that experience early graft loss, a number without dispersion.
- Patients Completing the Intended Therapy in Both Arms [2 years]
The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion
Eligibility Criteria
Criteria
Ages Eligible for Study:
50 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
INCLUSION CRITERIA
-
≥ 50 years of age and ≤ 75 years of age.
-
De novo acute myelogenous leukemia (AML), based on FAB and WHO criteria.
-
Intermediate or unfavorable cytogenetic abnormalities based on Southwest Oncology Group (SWOG) Cytogenetic Criteria.
-
First morphologic complete remission (CR), or CRp (a complete remission but with low platelets) following 1 or 2 courses of induction therapy, documented no more than 8 weeks prior to the date of enrollment and confirmed at time of enrollment.
-
Karnofsky Performance Score ≥ 60.
-
Suitable for non-myeloablative transplantation or best treatment.
-
Able to understand and willing to sign a written informed consent document.
EXCLUSION CRITERIA
-
AML with favorable cytogenetic features based on SWOG Cytogenetic Criteria
-
AML, either treatment-related or MDS-related
-
Active CNS disease as identified by positive CSF cytospin at time of enrollment.
-
Prior or concurrent malignancies except localized non-melanoma skin malignancies or treated cervical carcinoma in situ. (EXCEPTION: Cancer treated with curative intent > 5 years previously is allowed. EXCEPTION: Low grade lymphoma is allowed as long as active treatment is not required for control of disease)
-
Planned for allogeneic transplant using a full-dose conditioning
-
Life expectancy < 1 year due to diseases other than malignancy
-
Pregnant or breastfeeding.
-
HIV-seropositive.
-
Uncontrolled infection (presumed or documented) with progression after appropriate therapy for greater than one month.
-
Symptomatic coronary artery disease or uncontrolled congestive heart failure. Left ventricular ejection fraction (LVEF) is not required to be measured, however if measured, exclusion if ejection fraction is < 30%.
-
Requiring supplementary continuous oxygen. Diffusing capacity of the lungs for carbon monoxide (DLCO) is not required to be measured, however if it is measured, exclusion if DLCO < 35%.
-
Fulminant liver failure
-
Cirrhosis with evidence of portal hypertension or bridging fibrosis
-
Alcoholic hepatitis
-
Esophageal varices
-
A history of bleeding esophageal varices
-
Hepatic encephalopathy
-
Uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time
-
Ascites related to portal hypertension
-
Chronic viral hepatitis with total serum bilirubin > 3 mg/dL
-
Symptomatic biliary disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Kaiser Permanente Northern California | Hayward | California | United States | 94545 |
| 2 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | Univeristy of California Davis Medical Center | Sacramento | California | United States | 95817 |
| 4 | Stanford University School of Medicine | Stanford | California | United States | 94305 |
| 5 | West Virginia University Hospital | Morgantown | West Virginia | United States | 26506 |
Sponsors and Collaborators
- Stanford University
- Genzyme, a Sanofi Company
Investigators
- Principal Investigator: Robert Lowsky, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Robert Lowsky,
Professor of Medicine,
Stanford University
ClinicalTrials.gov Identifier:
NCT00568633
Other Study ID Numbers:
- IRB-05567
- 97843
- BMT190
First Posted:
Dec 6, 2007
Last Update Posted:
Sep 24, 2019
Last Verified:
Aug 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Period Title: Overall Study | ||
| STARTED | 25 | 33 |
| COMPLETED | 25 | 33 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care | Total |
|---|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation | Total of all reporting groups |
| Overall Participants | 25 | 33 | 58 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
20
80%
|
26
78.8%
|
46
79.3%
|
| >=65 years |
5
20%
|
7
21.2%
|
12
20.7%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
60
(5.1)
|
60
(6)
|
60
(5.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
11
44%
|
11
33.3%
|
22
37.9%
|
| Male |
14
56%
|
22
66.7%
|
36
62.1%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
3
9.1%
|
3
5.2%
|
| Not Hispanic or Latino |
25
100%
|
30
90.9%
|
55
94.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
1
3%
|
1
1.7%
|
| Asian |
2
8%
|
5
15.2%
|
7
12.1%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
2
6.1%
|
2
3.4%
|
| Black or African American |
0
0%
|
2
6.1%
|
2
3.4%
|
| White |
22
88%
|
21
63.6%
|
43
74.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
1
4%
|
2
6.1%
|
3
5.2%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
25
100%
|
33
100%
|
58
100%
|
Outcome Measures
| Title | Overall Survival (OS) |
|---|---|
| Description | Overall survival defined as the time interval between the date of attaining a first complete remission (CR) and the date of death from any cause. The outcome is reported as the number of participants alive (without dispersion). |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 33 |
| Count of Participants [Participants] |
9
36%
|
13
39.4%
|
| Title | Disease-free Survival (DFS) |
|---|---|
| Description | Disease-free survival is defined as the time interval between the date of attaining a first complete remission (CR) and the date of relapse. Disease free survival (DFS) will compared to conventional therapy vs Non-myeloablative Host Conditioning (NMA HCT). The outcome is reported as the number of participants which never experienced disease relapse (without dispersion). |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 33 |
| Count of Participants [Participants] |
5
20%
|
9
27.3%
|
| Title | Non-relapse Mortality |
|---|---|
| Description | Non-relapse mortality is defined as death that occurs after therapy, from any cause except a cause associated with relapse. This will be reported as the number of participants experiencing non-relapse mortality (a number without dispersion). |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 33 |
| Count of Participants [Participants] |
1
4%
|
2
6.1%
|
| Title | Relapse Rate |
|---|---|
| Description | Relapse will be determined as ≥ 5% blast cells in the bone marrow, not secondary to regeneration after myelosuppressive therapy; OR emergence of extramedullary leukemia; OR the re-emergence of blasts in the peripheral blood. The outcome will be reported as the number and percentage of participants that meet these criteria (a number without dispersion). |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 33 |
| Count of Participants [Participants] |
20
80%
|
24
72.7%
|
| Title | Transplant-related Mortality |
|---|---|
| Description | Transplant-related mortality will be assessed as any death occurring within 6 months post-transplant, from any cause except relapse. It will be measured at 100 day and 6 months after transplant. The outcome is expressed as at the number of participants experiencing transplant-related mortality (a number without dispersion). |
| Time Frame | 100 days and 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Best Standard Care arm did not receive transplant, and are not evaluable for transplant outcomes. |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 0 |
| At 100 days |
0
0%
|
|
| At 6 months |
1
4%
|
| Title | Complete Donor Hematopoietic Cell Chimerism |
|---|---|
| Description | Complete donor hematopoietic cell chimerism was evaluated in transplant recipients. Complete donor chimerism will be assessed as the presence of > 95% donor T-cells (CD3+) in the blood. The outcome is reported as the percentage of participants that achieve complete donor chimerism, a number without dispersion. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Best Standard Care arm did not receive transplant, and are not evaluable for transplant outcomes. |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 0 |
| Number [percentage of participants] |
56
224%
|
| Title | Early Graft Loss |
|---|---|
| Description | Early graft loss means a failure to achieve donor T-cell chimerism of > 5% at any time after transplant. The outcome is reported as the percentage of participants that experience early graft loss, a number without dispersion. |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the Best Standard Care arm did not receive transplant, and are not evaluable for transplant outcomes. |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 0 |
| Number [percentage of participants] |
4
16%
|
| Title | Patients Completing the Intended Therapy in Both Arms |
|---|---|
| Description | The assessment for completion of the intended therapy (in both arms) will be reported as the percentage of participants, a number without dispersion |
| Time Frame | 2 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care |
|---|---|---|
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation |
| Measure Participants | 25 | 33 |
| Number [percentage of participants] |
100
400%
|
81.8
247.9%
|
Adverse Events
| Time Frame | 2 years | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Non-serious adverse events were not collected in this study. | |||
| Arm/Group Title | Allo-HSCT + TLI + ATG | Best Standard Care | ||
| Arm/Group Description | Participants achieving complete remission after consolidation therapy & who have 5 of 6 HLA-match sibling donor to provide PBSC harvest for transplant. Pre-transplant subjects receive: Total lymphoid radiation (TLI) Days -11 to -7, and Days -4 to -1 (2 fractions on day -1) Anti-thymocyte globulin (ATG) Days -11 to -7 Methylprednisolone Days -11 to -7 Cyclosporine (CSP) Days -4 to +2 5+ of 6 HLA-matched CD34+ cells on Day 0 Mycophenolate mofetil (MMF), Day 0 to Day +28 Allogeneic HSCT: Allogeneic, 5+ of 6 HLA-matched PBSC transplant from sibling, mobilized to target of 5 x 10e6 CD34+ cells/kg and < 7 x 10e8 CD3+ cells/kg. Anti-thymocyte globulin (ATG): 1.5 mg/kg for 5 days by IV Cyclosporine (CSP): 6.25 mg/kg twice daily oral Mycophenolate mofetil (MMF): 15 mg/kg twice daily oral Total lymphoid irradiation (TLI): 80 cGy/fraction radiotherapy in 10 fractions. Methylprednisolone sodium succinate: 1.0 mg/kg for 5 days by IV | Regular medical care for participants who achieve complete remission after standard consolidation therapy, but do not have a 5 of 6 HLA-match sibling donor. Treatment may consist of: Additional consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation Best standard care: Intervention consist of: Consolidation chemotherapy (3-4 cycles of cytarabine +/- an anthracycline agent, or other consolidation) Autologous transplantation Non-Myeloablative unrelated-donor transplant, +/- TLI and ATG conditioning Umbilical cord blood transplantation Haploidentical transplantation | ||
All Cause Mortality |
||||
| Allo-HSCT + TLI + ATG | Best Standard Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/25 (64%) | 20/33 (60.6%) | ||
Serious Adverse Events |
||||
| Allo-HSCT + TLI + ATG | Best Standard Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/25 (80%) | 24/33 (72.7%) | ||
| General disorders | ||||
| Death not otherwise specified | 1/25 (4%) | 1 | 1/33 (3%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Relapse, leukemia | 20/25 (80%) | 20 | 24/33 (72.7%) | 24 |
| Nervous system disorders | ||||
| Altered mental status | 1/25 (4%) | 1 | 0/33 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Allo-HSCT + TLI + ATG | Best Standard Care | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 0/33 (0%) | ||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Robert Lowsky, Professor of Medicine (Blood and Marrow Transplantation) |
|---|---|
| Organization | Stanford University |
| Phone | 650-725-8950 |
| rlowsky@stanford.edu |
Responsible Party:
Robert Lowsky,
Professor of Medicine,
Stanford University
ClinicalTrials.gov Identifier:
NCT00568633
Other Study ID Numbers:
- IRB-05567
- 97843
- BMT190
First Posted:
Dec 6, 2007
Last Update Posted:
Sep 24, 2019
Last Verified:
Aug 1, 2019