LCCC0510: Allogeneic Hematopoietic Cell Transplantation for Patients With Busulfex-based Regimen
Study Details
Study Description
Brief Summary
RATIONALE: Giving chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving a monoclonal antibody, alemtuzumab, before the transplant and tacrolimus after the transplant may stop this from happening.
PURPOSE: The phase I portion of this trial identified the maximum tolerated dose of busulfan after treating 40 patients on a dose-escalation scheme. We are now treating an additional 26 patients on the phase II portion of the trial at a Pharmacokinetic (PK)-directed dose of total area under curve (AUC) 6912 micrometer (uM)-min/24 hours. We transitioned to the Phase II portion of the study in October 2009.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
OBJECTIVES:
Primary
-
Phase I Objective: To identify the maximum tolerated dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine, ATG and methotrexate plus tacrolimus for GVHD prophylaxis
-
Phase II Objective: To determine the one-year disease-free survival (DFS) rate at the maximum tolerated dose identified during Phase I of the trial (target AUC 6912)
Secondary
-
Determine the overall and disease-free survival of patients treated with this regimen.
-
Determine the dose-limiting toxicities of this regimen in these patients.
-
Determine the capacity of test dosing of busulfan that would result in the desired area under the curve concentration exposure of patients receiving a full-dose busulfan regimen.
-
Determine the incidence of graft-vs-host disease and DNA chimerism between 1 month and 2 years post-transplantation in these patients.
-
Compare the overall survival (OS) and disease-free survival (DFS) rates for patients treated with Campath vs. patients treated with ATG/Methotrexate for GVHD control
OUTLINE: This is a non-randomized, open-label, parallel group study of busulfan. Patients are stratified according to donor relationship - matched related donor (MRD) vs matched unrelated donor (MUD).
- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours once within days -15 to -10 and then IV continuously over 90 hours on days -7 to -4. Patients with a MRD also receive Methotrexate (MTX) on Days +1, +3, and +6. Patients with a MUD receive ATG on Days -3 and -2 and MTX on Days +1, +3 and +6.
Phase I portion only: Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
-
Allogeneic peripheral blood stem cell transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on day 0. Patients then receive sargramostim (GM-CSF) subcutaneously beginning on day 5 and continuing until blood counts recover.
-
Graft-vs-host disease (GVHD) prophylaxis: Patients receive oral tacrolimus twice daily on days -1 to 180 or days -1 to 240.
-
Donor lymphocyte infusion (DLI): Patients who do not achieve CR, do not have GVHD, and have been off immunosuppressants for at least 30 days may receive up to 3 DLIs, at least 8 weeks apart, after completion of tacrolimus.
After the completion of study treatment, patients are followed periodically for up to 5 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GVHD prophylaxis Subjects with matched-related donors (MRDs) were treated with tacrolimus and methotrexate with or without alemtuzumab for graft vs host disease prophylaxis Subjects also receive busulfan and fludarabine . Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus. |
Biological: rabbit anti-thymocyte globulin (ATG)
.5 mg/kg on day -3 and 2.5 mg/kg on day -2
Biological: therapeutic allogeneic lymphocytes
minimum total cluster of differentiation (CD34+) cells of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on day 0
Drug: busulfan
PK-targeted continuous IV infusion over 90 hours on Days -7 to -4.
Drug: fludarabine phosphate
30 mg/m^2/day x 5 days intravenous piggyback (IVPB) over 30 minutes on Days -7 through -3
Drug: tacrolimus
The suggested starting dose is 0.03 mg/kg po bid starting on day -1
Procedure: allogeneic hematopoietic stem cell transplantation
A minimum total CD34+ cell dose of 3 x 10^6 cells/kg and maximum of 8 x 10^6 cells/kg will be infused on day 0
Procedure: peripheral blood stem cell transplantation
minimum total CD34+ cell dose of 3 x 10^6 cells/kg and a maximum of 8 x 10^6 cells/kg will be infused on day 0
Drug: methotrexate
5 mg/m^2 on days +1, +3 and +6
|
Outcome Measures
Primary Outcome Measures
- Three-year Relapse-free Survival (RFS) Rate at the Maximum Tolerated Dose Identified During Phase I of the Trial (Target AUC 6912) [Three years post-transplant]
Relapse is defined as new or increased sites of disease or positive one marrow after a complete response (CR). The RFS was calculated as the percentage of patients who were alive and without relapse at 3 years
- Number of Participants With Dose Limiting Toxicities (DLTs) [first 6 weeks or 42 days following stem cell infusion]
Dose limiting toxicity will be defined as any irreversible grade 3 or any grade 4 non-hematologic toxicity that is related to busulfan infusion and not graft vs host disease or late infection after recovery from the initial period of myelosuppression. The maximum tolerated dose (MTD) is defined as the dose with probability of dose limiting toxicity (DLT) of 0.25. The dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine and alemtuzumab plus tacrolimus for GVHD prophylaxis.
Secondary Outcome Measures
- Capacity of Test Dosing of Busulfan That Would Result in the Desired Area Under the Curve Concentration Exposure of Patients Receiving a Full-dose Busulfan Regimen [Day -15 to Day -11]
Test doses of busulfan were administered and plasma levels were measured to determine a targeted AUC dosing estimate. The capacity is reported as the precision with which these test dose goals predicted the actual 90-hour mean AUC levels.Dose targeting precision was estimated by root mean squared error.
- Incidence of Graft vs Host Disease in Patients Between One Month and Two Years Post Transplant [100 days post transplant]
GVHD can be mild, moderate or severe depending on the differences in tissue type between patient and donor. GVHD can be acute or chronic. Its symptoms can include: Rashes, which include burning and redness, that erupt on the palms or soles and may spread to the trunk and eventually to the entire body Blistering, causing the exposed skin surface to flake off in severe cases Nausea, vomiting, abdominal cramps, diarrhea and loss of appetite, which can indicate that the gastrointestinal (digestive) tract is affected Jaundice, or a yellowing of the skin, which can indicate liver damage Excessive dryness of the mouth and throat, leading to ulcers Dryness of the lungs, vagina and other surfaces
- Incidence of DNA Chimerism in Patients Between One Month Post Transplant [30 days post transplant]
Deoxyribonucleic acid (DNA) chimerism is a measure identifying the genetic profiles of the transplant recipient and of the donor and then evaluating the extent of mixture in the recipient's blood, bone marrow, or other tissue.
- Overall Survival [Three years post-transplant]
Percentage of participants alive at 3 years post transplant
Eligibility Criteria
Criteria
INCLUSION CRITERIA
Histologically confirmed diagnosis of any of the following:
Chronic lymphocytic leukemia or prolymphocytic leukemia Chemotherapy-refractory or advanced disease after ≥ 3 prior treatments Chronic myelogenous leukemia Diagnosis based on t(9;22) or related t(9;12) cytogenetic abnormalities AND characterized by elevated white blood counts (WBC) in peripheral blood or marrow Patients with progressive disease on imatinib mesylate or other protein tyrosine kinase inhibitors; less than a major cytogenetic or fluorescent in situ hybridization (FISH) complete response (CR) after a minimum of 6 months of targeted therapy; or less than a complete FISH or cytogenetic response after 12 months of targeted therapy are eligible Patients with other cytogenetic abnormalities, such as t(9;12), that are associated with an aggressive clinical course are eligible Non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma Any World Health Organization (WHO) classification histologic subtype allowed Must have advanced disease as defined by relapse after initial CR or failure to achieve CR OR deemed to have less than a 30% likelihood of durable response with an autologous stem cell transplant Refractory low-grade NHL histologies or any intermediate or aggressive large cell or mantle cell lymphoma allowed Acute myeloid leukemia (AML) High-risk disease in first CR (CR1) OR evidence of any recurrent disease beyond CR1 High-risk individuals are those requiring more than 1 course of induction therapy to achieve remission; those with extra-medullary disease at presentation; or those with high-risk cytogenetic abnormalities (abnormalities of chromosomes 5, 7, 2, trisomy 8, or 3) or > 2 cytogenetic abnormalities
-
Multiple myeloma
-
Myelodysplastic syndromes (MDS) Must have MDS defined by WHO criteria with > 5% blasts or high-risk cytogenetic abnormalities (abnormalities of chromosomes 5, 7, 2, trisomy 8, or 3)
-
Acute lymphoblastic leukemia (ALL) High-risk disease in CR1 OR beyond CR1 High-risk disease includes the following: t(9;22) or t(4;11); WBC > 30,000/mm³ at presentation; non-T-cell phenotype; or more than 30 years of age
-
Myelofibrosis/agnogenic myeloid metaplasia
-
Patients must be transfusion dependant or have evidence of evolving AML as evidenced by an excess of blasts or a state of marrow failure/fibrosis
-
Myeloproliferative disorders with advanced disease (e.g., progressive or spent phase polycythemia vera, myelofibrosis, or essential thrombocythemia)
-
Any of the following categories of donors are acceptable*:
-
Human Leucocyte Antigen (HLA)-identical or 1 antigen-mismatched sibling (5/6, 6/6, or 8/10) donor
-
Minimal serologic typing required for class I (A, B); molecular typing required for class II (DRB1)
-
8/10 matched unrelated donor (MUD)
-
Molecular analysis at HLA-A, -B, -C, -DRB1 and -DQB1 (8/10 match) by high resolution typing is required
-
5/6 MUD
-
Molecular analysis at HLA-A, -B, and -DRB1 required Note: *No syngeneic donors
PATIENT CHARACTERISTICS:
-
Performance status 0-2
-
Bilirubin ≤ 2 times upper limit of normal (ULN)
-
Aspartate aminotransferase (AST) ≤ 2 times ULN
-
Creatinine clearance ≥ 50 mL/min
-
Not pregnant or nursing
-
Negative pregnancy test
-
Fertile patients must use effective contraception
-
Diffusing capacity of the lungs for carbon monoxide (DLCO) > 60% with no symptomatic pulmonary disease
-
Left ventricular ejection fraction (LVEF) ≥ 50% by multigated acquisition (MUGA) scan
EXCLUSION CRITERIA Uncontrolled or severe cardiovascular disease, pulmonary disease, or infection that, in the opinion of the treating physician, would make this study unreasonably hazardous to the patient Other serious illness that would limit survival to < 2 years Psychiatric condition that would preclude study compliance Uncontrolled diabetes mellitus or active serious infection Active second malignancy except for nonmelanomatous skin cancer Known hypersensitivity to E. coli-derived products HIV positivity
PRIOR CONCURRENT THERAPY:
-
See Disease Characteristics
-
More than 4 weeks since prior chemotherapy, radiotherapy, or surgery
-
Cranial radiotherapy or intrathecal therapy as prophylaxis against central nervous system (CNS) recurrence within the past 4 weeks allowed (in high-risk patients)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill | North Carolina | United States | 27599-7295 |
Sponsors and Collaborators
- UNC Lineberger Comprehensive Cancer Center
- National Cancer Institute (NCI)
- Otsuka America Pharmaceutical
Investigators
- Principal Investigator: Thomas C. Shea, MD, UNC Lineberger Comprehensive Cancer Center
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- LCCC 0510
- P30CA016086
- NCT00618306
Study Results
Participant Flow
| Recruitment Details | Patients with advanced, refractory, or high-risk hematologic cancers who were deemed suitable for myeloablative conditioning were recruited from one institution. |
|---|---|
| Pre-assignment Detail | A total of 55 subjects were consented, but one subject was not enrolled due to disease progression or death prior to protocol therapy. |
| Arm/Group Title | Experimental: GVHD Prophylaxis |
|---|---|
| Arm/Group Description | Experimental: GVHD prophylaxis Subjects with matched-related donors (MRDs) were treated with tacrolimus and methotrexate with or without alemtuzumab for graft vs host disease prophylaxis Subjects also receive busulfan and fludarabine . Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus. |
| Period Title: Overall Study | |
| STARTED | 54 |
| COMPLETED | 54 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Experimental: GVHD Prophylaxis |
|---|---|
| Arm/Group Description | Experimental: GVHD prophylaxis Subjects with matched-related donors (MRDs) were treated with tacrolimus and methotrexate with or without alemtuzumab for graft vs host disease prophylaxis Subjects also receive busulfan and fludarabine . Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus. |
| Overall Participants | 54 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
50
|
| Sex: Female, Male (Count of Participants) | |
| Female |
20
37%
|
| Male |
34
63%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
1
1.9%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
5.6%
|
| White |
48
88.9%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
2
3.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
54
100%
|
| Donor-recipient sex (Count of Participants) | |
| Male-Female |
6
11.1%
|
| Female-Male |
12
22.2%
|
| Male-Male |
22
40.7%
|
| Female-Female |
14
25.9%
|
| Host cytomegalovirus (CMV) status (Count of Participants) | |
| Negative |
18
33.3%
|
| Positive |
36
66.7%
|
| Disease histology (Count of Participants) | |
| Myelogenous leukemia |
26
48.1%
|
| Myelodysplasia |
8
14.8%
|
| Chronic myelogenous leukemia |
1
1.9%
|
| Acute lymphoblastic leukemia |
7
13%
|
| Non-Hodgkin Lymphoma |
5
9.3%
|
| Hodgkin lymphoma |
2
3.7%
|
| Myelofibrosis |
1
1.9%
|
| Chronic lymphoblastic leukemia |
1
1.9%
|
| Chronic myelomonocytic leukemia |
1
1.9%
|
| Plastic cell leukemia |
2
3.7%
|
| Type of transplant (Count of Participants) | |
| Matched unrelated donor (MUD) |
34
63%
|
| Matched unrelated donor (MRD) |
20
37%
|
| Disease risk (Count of Participants) | |
| Low |
16
29.6%
|
| Intermediate |
20
37%
|
| High |
18
33.3%
|
Outcome Measures
| Title | Three-year Relapse-free Survival (RFS) Rate at the Maximum Tolerated Dose Identified During Phase I of the Trial (Target AUC 6912) |
|---|---|
| Description | Relapse is defined as new or increased sites of disease or positive one marrow after a complete response (CR). The RFS was calculated as the percentage of patients who were alive and without relapse at 3 years |
| Time Frame | Three years post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Because AUC levels varied between the groups and the goal was to identify an actual achieved AUC-based dose, additional outcome analyses were undertaken by dividing patients into thirds according to the actual AUCs delivered rather than the original planned AUCs. |
| Arm/Group Title | Low Busulfan AUC Tertile | Intermediate Busulfan AUC Tertile | High Busulfan AUC Tertile |
|---|---|---|---|
| Arm/Group Description | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 5078 (full range 3933-5615) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 6372 (full range 5639-6965) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 7605 (full range 7054-8863) microM/min |
| Measure Participants | 18 | 18 | 18 |
| Number [percentage of participants] |
22
40.7%
|
39
NaN
|
43
NaN
|
| Title | Number of Participants With Dose Limiting Toxicities (DLTs) |
|---|---|
| Description | Dose limiting toxicity will be defined as any irreversible grade 3 or any grade 4 non-hematologic toxicity that is related to busulfan infusion and not graft vs host disease or late infection after recovery from the initial period of myelosuppression. The maximum tolerated dose (MTD) is defined as the dose with probability of dose limiting toxicity (DLT) of 0.25. The dose of continuous infusion IV busulfan based on blood levels derived from a test dose in conjunction with fludarabine and alemtuzumab plus tacrolimus for GVHD prophylaxis. |
| Time Frame | first 6 weeks or 42 days following stem cell infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 |
|---|---|---|---|---|---|
| Arm/Group Description | Target AUC/24 hrs of 4800 micrometer (uM)-min +/-15% | Target AUC/24 hrs of 5760 uM-min +/- 15% | Target AUC/24 hrs of 6912 uM-min +/- 15% | Target AUC/24 hrs of 7603 uM-min+/- 15% | Target AUC/24 hrs of 8363 uM-min+/- 15% |
| Measure Participants | 14 | 7 | 24 | 7 | 2 |
| Number [DLTs] |
1
|
1
|
1
|
2
|
2
|
| Title | Capacity of Test Dosing of Busulfan That Would Result in the Desired Area Under the Curve Concentration Exposure of Patients Receiving a Full-dose Busulfan Regimen |
|---|---|
| Description | Test doses of busulfan were administered and plasma levels were measured to determine a targeted AUC dosing estimate. The capacity is reported as the precision with which these test dose goals predicted the actual 90-hour mean AUC levels.Dose targeting precision was estimated by root mean squared error. |
| Time Frame | Day -15 to Day -11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Dose Level 5 |
|---|---|---|---|---|---|
| Arm/Group Description | Target AUC/24 hrs of 4800 uM-min +/-15% | Target AUC/24 hrs of 5760 uM-min +/- 15% | Target AUC/24 hrs of 6912 uM-min +/- 15% | Target AUC/24 hrs of 7603 uM-min+/- 15% | Target AUC/24 hrs of 8363 uM-min+/- 15% |
| Measure Participants | 14 | 7 | 24 | 7 | 2 |
| Number [percentage of error] |
11.7
|
4.9
|
10.2
|
11.1
|
15.9
|
| Title | Incidence of Graft vs Host Disease in Patients Between One Month and Two Years Post Transplant |
|---|---|
| Description | GVHD can be mild, moderate or severe depending on the differences in tissue type between patient and donor. GVHD can be acute or chronic. Its symptoms can include: Rashes, which include burning and redness, that erupt on the palms or soles and may spread to the trunk and eventually to the entire body Blistering, causing the exposed skin surface to flake off in severe cases Nausea, vomiting, abdominal cramps, diarrhea and loss of appetite, which can indicate that the gastrointestinal (digestive) tract is affected Jaundice, or a yellowing of the skin, which can indicate liver damage Excessive dryness of the mouth and throat, leading to ulcers Dryness of the lungs, vagina and other surfaces |
| Time Frame | 100 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Because AUC levels varied between the groups and the goal was to identify an actual achieved AUC-based dose, additional outcome analyses were undertaken by dividing patients into thirds according to the actual AUCs delivered rather than the original planned AUCs. |
| Arm/Group Title | Low Busulfan AUC Tertile | Intermediate Busulfan AUC Tertile | High Busulfan AUC Tertile |
|---|---|---|---|
| Arm/Group Description | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 5078 (full range 3933-5615) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 6372 (full range 5639-6965) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 7605 (full range 7054-8863) microM/min |
| Measure Participants | 18 | 18 | 18 |
| Acute GVHD grade >=II |
7
13%
|
10
NaN
|
11
NaN
|
| Acute GVHD grades III and IV |
2
3.7%
|
4
NaN
|
3
NaN
|
| Chronic GVHD; intermediate/severe |
4
7.4%
|
6
NaN
|
2
NaN
|
| Title | Incidence of DNA Chimerism in Patients Between One Month Post Transplant |
|---|---|
| Description | Deoxyribonucleic acid (DNA) chimerism is a measure identifying the genetic profiles of the transplant recipient and of the donor and then evaluating the extent of mixture in the recipient's blood, bone marrow, or other tissue. |
| Time Frame | 30 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Because there were no differences in chimerism results as a function of either the immunosuppression used or busulfan dose received, the results are being reported only for the total population. |
| Arm/Group Title | Experimental: GVHD Prophylaxis |
|---|---|
| Arm/Group Description | Matched related donor (MRD) subjects receive Graft Vs Host Disease (GVHD )prophylaxis with Methotrexate alone Subjects also receive busulfan, fludarabine, and tacrolimus and may receive Alemtuzumab. Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus. |
| Measure Participants | 54 |
| Whole blood chimerism-Any |
49
90.7%
|
| Whole blood chimerism->=95% donor |
47
87%
|
| T Cell chimerism-Any |
46
85.2%
|
| T Cell chimerism>=95% donor |
30
55.6%
|
| Title | Overall Survival |
|---|---|
| Description | Percentage of participants alive at 3 years post transplant |
| Time Frame | Three years post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Because AUC levels varied between the groups and the goal was to identify an actual achieved AUC-based dose, additional outcome analyses were undertaken by dividing patients into thirds according to the actual AUCs delivered rather than the original planned AUCs. |
| Arm/Group Title | Low Busulfan AUC Tertile (5078) | Intermediate Busulfan AUC Tertile (6372) | High Busulfan AUC Tertile (7605) |
|---|---|---|---|
| Arm/Group Description | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 5078 (full range 3933-5615) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 6372 (full range 5639-6965) microM/min | Participants with the lowest tertile of measured busulfan Area under the curve (AUC); with a mean value of 7605 (full range 7054-8863) microM/min |
| Measure Participants | 18 | 18 | 18 |
| Number [percentage of participants] |
28
51.9%
|
39
NaN
|
55
NaN
|
Adverse Events
| Time Frame | Mortality was assessed at one year | |
|---|---|---|
| Adverse Event Reporting Description | Additional toxicities were not captured as this was a high-dose transplant study and grades 1, 2 and 3 AEs were generally expected and no unexpected toxicities were seen beyond those reported as SAEs | |
| Arm/Group Title | Experimental: GVHD Prophylaxis | |
| Arm/Group Description | Experimental: GVHD prophylaxis Subjects with matched-related donors (MRDs) were treated with tacrolimus and methotrexate with or without alemtuzumab for graft vs host disease prophylaxis Subjects also receive busulfan and fludarabine . Matched unrelated donor (MUD) or mismatched related donor (MMRD) subjects receive GVHD prophylaxis with rabbit anti-thymocyte globulin (ATG) + Methotrexate Subjects also receive busulfan, fludarabine, and tacrolimus. | |
All Cause Mortality |
||
| Experimental: GVHD Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 15/54 (27.8%) | |
Serious Adverse Events |
||
| Experimental: GVHD Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 26/54 (48.1%) | |
| Blood and lymphatic system disorders | ||
| Graft Failure | 1/54 (1.9%) | |
| anemia | 1/54 (1.9%) | |
| thrombocytopenia | 4/54 (7.4%) | |
| Endocrine disorders | ||
| Glucose Intolerance | 1/54 (1.9%) | |
| Gastrointestinal disorders | ||
| Gr 4 GVHD | 1/54 (1.9%) | |
| Gr 4 mucositis | 5/54 (9.3%) | |
| Hepatobiliary disorders | ||
| Liver Failiure | 1/54 (1.9%) | |
| Veno-occlusive disease | 3/54 (5.6%) | |
| Infections and infestations | ||
| BK cystitis | 1/54 (1.9%) | |
| Sepsis | 4/54 (7.4%) | |
| Aspergillus pneumonia | 2/54 (3.7%) | |
| CMV pneumonitis | 1/54 (1.9%) | |
| Renal and urinary disorders | ||
| renal Failure | 2/54 (3.7%) | |
| Respiratory, thoracic and mediastinal disorders | ||
| Diffuse alveolar hemorrhage | 1/54 (1.9%) | |
| acute respiratory failure | 1/54 (1.9%) | |
| Vascular disorders | ||
| left neck hematoma | 1/54 (1.9%) | |
Other (Not Including Serious) Adverse Events |
||
| Experimental: GVHD Prophylaxis | ||
| Affected / at Risk (%) | # Events | |
| Total | 54/54 (100%) | |
| Blood and lymphatic system disorders | ||
| grade 3 or 4 hematologic toxicities (expected) | 54/54 (100%) | |
| Gastrointestinal disorders | ||
| grade 3 GI toxicity | 21/54 (38.9%) | |
| Skin and subcutaneous tissue disorders | ||
| Alopecia | 54/54 (100%) | |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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 | Dr. Thomas Shea |
|---|---|
| Organization | UNC Lineberger Comprehensive Cancer Center |
| Phone | 919-966-7746 |
| tom_shea@med.unc.edu |
- LCCC 0510
- P30CA016086
- NCT00618306