Fludarabine-IV Busulfan ± Clofarabine and Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)
Study Details
Study Description
Brief Summary
The goal of this clinical research study is to learn if combining busulfan with clofarabine and fludarabine can help control the disease better than the previous standard method (using busulfan and fludarabine alone) in patients with AML or MDS. The safety of this combination therapy will also be studied.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Busulfan is designed to kill cancer cells by binding to DNA (the genetic material of cells), which may cause cancer cells to die. Busulfan is commonly used in stem cell transplantation.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Fludarabine is designed to interfere with the DNA of cancer cells, which may cause the cancer cells to die.
Study Groups:
You will be randomly assigned (as in the toss of a coin) to 1 of 2 study groups.
-
Group 1 will receive busulfan, fludarabine, and clofarabine.
-
Group 2 will receive busulfan and fludarabine.
Both groups will have a stem cell transplant. The stem cells will be given by vein. The cells will travel to your bone marrow where they are designed to make healthy, new blood cells after several weeks.
For a stem cell transplant, the days before you receive your stem cells are called minus days. The day you receive the stem cells is called Day 0. The days after you receive the stem cells are called plus days.
Study Drug Administration and Procedures:
Both groups will receive a "test" dose of busulfan by vein over about 45 minutes to 1 hour. This low-level test dose of busulfan is to check how fast busulfan is processed by your body and cleared from your blood. This information will determine the amount of busulfan you will receive. You may receive the busulfan test dose as an outpatient during the week before you are admitted to the hospital or as an inpatient 8 days before your stem cell transplant.
About 11 samples of blood (about 1 teaspoon each time) will be drawn for pharmacokinetic (PK) testing. PK testing measures the amount of study drug in the body at different time points and will also help determine your dose of busulfan. These blood samples will be drawn at various times before you receive busulfan and over the next 11 hours. These blood draws will be repeated again on the first day of high-dose busulfan treatment (Day -6, which is 6 days before the transplant).
A heparin lock line will be placed in your vein to lower the number of needle sticks needed for these draws. If it is not possible for the PK tests to be performed for technical or scheduling reasons, you will receive the standard fixed dose of busulfan.
On Days -6 through -3, you will receive fludarabine by vein over 1 hour, then clofarabine (if you are in Group 1) by vein over 1 hour, then busulfan by vein over 3 hours.
After the transplant, you will receive tacrolimus, methotrexate, or other immunosuppressive (lowering the immune system) drugs in the standard manner to lower the risk of graft-vs-host disease (GvHD), a reaction of the donor's immune cells against the recipient's body.
If you are going to be receiving a transplant from an HLA-nonidentical or unrelated donor, you will also receive antithymocyte globulin (ATG) by vein over 4 hours on the 3 days before the transplant. This drug is designed to further weaken your immune system to reduce the risk of rejecting of the transplant.
You will receive filgrastim as an injection under the skin 1 time a day, starting 1 week after the transplant, until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.
While you are in the hospital, you will be checked for any side effects as part of your standard of care. Blood (about 2 teaspoons) will be drawn every day to check for side effects, for routine tests, to check your blood counts, kidney and liver function, and to check for infections.
As part of standard care, you will remain in the hospital for about 3-4 weeks after transplant. After you are released from the hospital, you must remain in the Houston area to be monitored for infections and other transplant side effects until about 3 months after transplant. During this time, you will return to the clinic at least 1 time each week. The following tests and procedures will be performed:
-
You will be asked about how you are feeling and about any side effects you may be having.
-
Blood (about 2 teaspoons) will be drawn for routine tests.
Around 14-30 days after the transplant (when the transplant "engrafts", or "takes"), you will have a bone marrow aspirate to check the status of the disease.
Around Day 30, and about 3, 6, and 12 months after the transplant, the following tests and procedures will be performed:
-
You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate).
-
You will be asked about how you are feeling and about any side effects you may be having.
-
Blood (about 2 teaspoons) will be drawn to see how well the transplant has taken.
-
You will have a bone marrow aspiration to check the status of the disease. To collect a bone marrow aspiration, an area of the hip or other site is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.
Length of Study:
You will be taken off study 5 years after the end of treatment. You may be taken off study early if the disease gets worse, if you have any intolerable side effects, of if you are unable to follow study directions.
You should talk to the study doctor if you want to leave the study early. If you are taken off study early, you still may need to return for routine post-transplant follow-up visits, if your transplant doctor decides it is needed.
It may be life-threatening to leave the study after you have begun to receive the study drugs but before you receive the stem cells.
This is an investigational study. Busulfan and fludarabine are both FDA approved and commercially available for the treatment of AML and MDS. Clofarabine is FDA approved for treating other types of cancer, but is being used in AML and MDS for research only. The use of these study drugs together at the dose level used in this study is investigational.
Up to 250 patients will take part in this study. All will be enrolled at MD Anderson.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Flu + Bu Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. |
Drug: Fludarabine
Flu + Bu Group: 40 mg/m2 by vein on Days -6 through -3.
Flu +Clo + Bu Group: 10 mg/m2 by vein on Days -6 through -3.
Other Names:
Drug: Busulfan
Busulfan systemic exposure dose of 6000 µMol-min in normal saline over three (3) hours by vein every twenty-four (24) hours for four (4) consecutive days (days -6 to -3), starting immediately after the completion of Clofarabine. The dose on day -6 to -3 based on pharmacokinetic analysis of target AUC of 4,000 µMol-min ± 5% for 61-70 years of age (without Pharmacokinetics alternate dose 130 mg/m2).
Other Names:
Drug: Thymoglobulin
Both groups who receive a graft from an unrelated donor:
0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.0 mg/kg on day -1. On day -3, administered after the chemotherapy is complete.
Other Names:
Procedure: Stem Cell Infusion
Cryopreserved bone marrow or peripheral blood progenitor cells infused on day 0.
Other Names:
Drug: Tacrolimus
Starting dose: 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.
Other Names:
Drug: Methotrexate
5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.
|
| Experimental: Flu +Clo + Bu Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
Drug: Fludarabine
Flu + Bu Group: 40 mg/m2 by vein on Days -6 through -3.
Flu +Clo + Bu Group: 10 mg/m2 by vein on Days -6 through -3.
Other Names:
Drug: Clofarabine
30 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, and infused on Days -6 through -3.
Other Names:
Drug: Busulfan
Busulfan systemic exposure dose of 6000 µMol-min in normal saline over three (3) hours by vein every twenty-four (24) hours for four (4) consecutive days (days -6 to -3), starting immediately after the completion of Clofarabine. The dose on day -6 to -3 based on pharmacokinetic analysis of target AUC of 4,000 µMol-min ± 5% for 61-70 years of age (without Pharmacokinetics alternate dose 130 mg/m2).
Other Names:
Drug: Thymoglobulin
Both groups who receive a graft from an unrelated donor:
0.5 mg/kg on day -3, 1.5 mg/kg on day -2 and 2.0 mg/kg on day -1. On day -3, administered after the chemotherapy is complete.
Other Names:
Procedure: Stem Cell Infusion
Cryopreserved bone marrow or peripheral blood progenitor cells infused on day 0.
Other Names:
Drug: Tacrolimus
Starting dose: 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Changed to oral dosing when tolerated and can be tapered off after day +90 if no graft versus host disease (GVHD) present.
Other Names:
Drug: Methotrexate
5 mg/m2 by vein on Days 1, 3, 6 and 11 post transplant.
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) [From day of transplant to disease of progression or death of any cause, whichever came first, assessed up to 5 years]
Number of events with progression free survival. (Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.) or expired from treatment related mortality post transplant.
Secondary Outcome Measures
- Overall Survival (OS) Post Transplant at 1, 3 and 5 Years [Post transplant after 1, 3 and 5 years]
Number of participants in the study who are alive and disease free at 1, 3 and 5 years post transplant.
- Number of Participants in the Study Who Are With no Grade 3 or 4 Acute Graft-versus-host Disease at Any Time During the First 100 Days Post Transplant. [100 days post transplant]
Number of participants in the study who are with no Grade 3 or 4 acute graft-versus-host disease at any time during the first 100 days post transplant.
- Number of Participants With Non Relapse Mortality at 100 Day Post Transplant [100 day Post Transplant]
Number of participants expired from complications other than relapsed disease at 100 day Post Transplant.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patients must have one of the following hematologic malignancies: a) Acute myeloid leukemia (AML) any stage and cytogenetic risk-group with the only exception being that patients with AML and favorable cytogenetics (t(8;21, inv 16, or t(15;17) who achieve complete remission with one course of induction chemotherapy are not eligible . Patients with treatment related AML are eligible. b) Myelodysplastic syndromes (MDS) with intermediate or high risk International Prognostic Scoring System score (IPSS scores) or treatment related MDS. Patients with low risk MDS are eligible if they fail to respond to hypomethylating agent therapy such as azacitidine or decitabine.
-
Age 3-70 years old. Eligibility for pediatric patients will be determined in conjunction with an MDACC pediatrician.
-
Performance score of >/= 60 by Karnofsky or PS 0 to 2 (ECOG) (age > 12 years), or Lansky Play-Performance Scale >/= 60 or greater (age <12 years).
-
Negative Beta HCG test in a woman with child bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization. Women of child bearing potential must be willing to use an effective contraceptive measure while on study.
-
Adequate major organ system function as demonstrated by: Left ventricular ejection fraction of at least 40%.
-
Pulmonary function test (PFT) demonstrating a diffusion capacity of least 50% predicted. For children </=7 years of age who are unable to perform PFT, oxygen saturation >/=92% on room air by pulse oximetry.
-
Creatinine < 1.5 mg/dL. If question about renal function discuss with study chairman and do 24 hour creatinine clearance (clearance should be >50 ml/min).
-
Bilirubin < to 2.0 x normal (except Gilbert's Syndrome). SGPT (ALT) < 200. No evidence of chronic active hepatitis or cirrhosis.
-
Histocompatible stem cell donor: Patients must have an HLA matched related or unrelated donor (HLA A, B, C and DR) willing to donate for allogeneic hematopoietic transplantation. High resolution allele level typing is required for donors other than genotypically identical siblings.
-
No uncontrolled infection. Protocol PI or designé will be final arbiter if there is uncertainty regarding whether a previous infection is controlled on appropriate (antibiotic) therapy.
-
Patient or patient's legal representative, parent(s) or guardian able to sign informed consent.
Exclusion Criteria:
-
Positive for HIV, HBsAg, HCV or other viral hepatitis or cirrhosis from any cause.
-
Prior allogeneic or autologous stem cell transplant using a myeloablative busulfan or total body radiation containing conditioning regimen defined as busulfan-based using a total dose of >/=12 mg/kg given by mouth or >/=10 mg/kg given IV; or a total-body irradiation (> 4 Gy).
-
Active or prior CNS leukemia, unless in complete remission for at least 3 months.
-
Previous therapeutic XRT to the liver as part of involved-field radiation.
-
History of serious chronic mental disorder or drug-abuse accompanied by documented problems of compliance with therapeutic programs.
-
Lack of care-giver for the early (100-day) post-transplant period.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- M.D. Anderson Cancer Center
- Sanofi
Investigators
- Principal Investigator: Richard E. Champlin, BS,MD, M.D. Anderson Cancer Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 2011-0628
- NCI-2012-00038
Study Results
Participant Flow
| Recruitment Details | Participants recruitment from November 2011 to August 2015 at MD Anderson Cancer Center |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) |
|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
| Period Title: Overall Study | ||
| STARTED | 133 | 123 |
| COMPLETED | 130 | 120 |
| NOT COMPLETED | 3 | 3 |
Baseline Characteristics
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) | Total |
|---|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | FlFludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. | Total of all reporting groups |
| Overall Participants | 130 | 120 | 250 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
2
1.7%
|
2
0.8%
|
| Between 18 and 65 years |
105
80.8%
|
103
85.8%
|
208
83.2%
|
| >=65 years |
25
19.2%
|
15
12.5%
|
40
16%
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
54
41.5%
|
55
45.8%
|
109
43.6%
|
| Male |
76
58.5%
|
65
54.2%
|
141
56.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
4
3.1%
|
3
2.5%
|
7
2.8%
|
| Native Hawaiian or Other Pacific Islander |
1
0.8%
|
0
0%
|
1
0.4%
|
| Black or African American |
5
3.8%
|
3
2.5%
|
8
3.2%
|
| White |
120
92.3%
|
114
95%
|
234
93.6%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | |||
| United States |
127
97.7%
|
119
99.2%
|
246
98.4%
|
| Saudi Arabia |
2
1.5%
|
1
0.8%
|
3
1.2%
|
| Qatar |
1
0.8%
|
0
0%
|
1
0.4%
|
Outcome Measures
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | Number of events with progression free survival. (Progression is defined as more than 5% blast in the peripheral blood or bone marrow biopsy.) or expired from treatment related mortality post transplant. |
| Time Frame | From day of transplant to disease of progression or death of any cause, whichever came first, assessed up to 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) |
|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
| Measure Participants | 130 | 120 |
| Number [Number of events] |
69
|
61
|
| Title | Overall Survival (OS) Post Transplant at 1, 3 and 5 Years |
|---|---|
| Description | Number of participants in the study who are alive and disease free at 1, 3 and 5 years post transplant. |
| Time Frame | Post transplant after 1, 3 and 5 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) |
|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
| Measure Participants | 130 | 120 |
| 1 Year Post Transplant |
83
63.8%
|
82
68.3%
|
| 3 Year Post Transplant |
69
53.1%
|
69
57.5%
|
| 5 Year Post Transplant |
64
49.2%
|
63
52.5%
|
| Title | Number of Participants in the Study Who Are With no Grade 3 or 4 Acute Graft-versus-host Disease at Any Time During the First 100 Days Post Transplant. |
|---|---|
| Description | Number of participants in the study who are with no Grade 3 or 4 acute graft-versus-host disease at any time during the first 100 days post transplant. |
| Time Frame | 100 days post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) |
|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0.. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
| Measure Participants | 130 | 120 |
| Count of Participants [Participants] |
125
96.2%
|
115
95.8%
|
| Title | Number of Participants With Non Relapse Mortality at 100 Day Post Transplant |
|---|---|
| Description | Number of participants expired from complications other than relapsed disease at 100 day Post Transplant. |
| Time Frame | 100 day Post Transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) |
|---|---|---|
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. |
| Measure Participants | 130 | 120 |
| Count of Participants [Participants] |
3
2.3%
|
6
5%
|
Adverse Events
| Time Frame | Through study completion, an average of 5 years. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) | ||
| Arm/Group Description | Fludarabine 40 mg/m2 intravenous (IV) over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours. Both delivered for 4 consecutive days (days -6 to -3). Stem cell transplant Day 0. | Fludarabine 10 mg/m2 over 1 hour. Clofarabine 40 mg/m2 diluted in normal saline to produce a final concentration of 0.4 mg/mL, infused over 1 hour. Busulfan dose calculated to achieve a systemic exposure dose of 6000 µMol-min IV for 60 years and younger or 4000 uMol-min IV for 61 years and older over 3 hours every 24 hours, immediately after Clofarabine. All delivered on 4 consecutive days (days -6 through -3). Stem cell transplant Day 0. | ||
All Cause Mortality |
||||
| Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 67/130 (51.5%) | 59/120 (49.2%) | ||
Serious Adverse Events |
||||
| Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 25/130 (19.2%) | 39/120 (32.5%) | ||
| Blood and lymphatic system disorders | ||||
| Transcient secondary graft failure | 1/130 (0.8%) | 1/120 (0.8%) | ||
| Thrombocytopenia | 2/130 (1.5%) | 2/120 (1.7%) | ||
| Poor graft function | 2/130 (1.5%) | 0/120 (0%) | ||
| ABO incompatibility | 1/130 (0.8%) | 0/120 (0%) | ||
| Gastrointestinal disorders | ||||
| GI GvHD | 2/130 (1.5%) | 4/120 (3.3%) | ||
| General disorders | ||||
| Diffused alveolar hemorrhage | 2/130 (1.5%) | 2/120 (1.7%) | ||
| Fluid overload | 0/130 (0%) | 1/120 (0.8%) | ||
| Hepatobiliary disorders | ||||
| Elevated transminitis | 1/130 (0.8%) | 1/120 (0.8%) | ||
| Ascites | 0/130 (0%) | 1/120 (0.8%) | ||
| VOD/SOS | 0/130 (0%) | 1/120 (0.8%) | ||
| Liver GvHD | 2/130 (1.5%) | 1/120 (0.8%) | ||
| Infections and infestations | ||||
| Bacterial Infections | 2/130 (1.5%) | 9/120 (7.5%) | ||
| Viral Infections | 4/130 (3.1%) | 3/120 (2.5%) | ||
| Fungal Infections | 2/130 (1.5%) | 4/120 (3.3%) | ||
| BK virus associated hemorrhagic cystitis | 0/130 (0%) | 1/120 (0.8%) | ||
| Investigations | ||||
| Hemochromatosis | 1/130 (0.8%) | 0/120 (0%) | ||
| Nervous system disorders | ||||
| Encephalopathy | 0/130 (0%) | 1/120 (0.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pneumonitis | 1/130 (0.8%) | 2/120 (1.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin GVHD | 2/130 (1.5%) | 2/120 (1.7%) | ||
| Vascular disorders | ||||
| Pulmonary embolism | 0/130 (0%) | 2/120 (1.7%) | ||
| DIC | 0/130 (0%) | 1/120 (0.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Arm A (Flu+Bu) | Arm B (Flu+Clo+Bu) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 123/130 (94.6%) | 120/120 (100%) | ||
| Blood and lymphatic system disorders | ||||
| ABO incompatibility | 4/130 (3.1%) | 0/120 (0%) | ||
| Thrombocytopenia | 0/130 (0%) | 2/120 (1.7%) | ||
| Cardiac disorders | ||||
| Cardiomyopathy | 2/130 (1.5%) | 0/120 (0%) | ||
| Dysrhythmia | 4/130 (3.1%) | 3/120 (2.5%) | ||
| Eye disorders | ||||
| Chronic ocular GvHD | 23/130 (17.7%) | 20/120 (16.7%) | ||
| Gastrointestinal disorders | ||||
| GI GvHD | 18/130 (13.8%) | 17/120 (14.2%) | ||
| Mucositis | 123/130 (94.6%) | 115/120 (95.8%) | ||
| Upper GI GvHD | 35/130 (26.9%) | 40/120 (33.3%) | ||
| Chronic oral GvHD | 20/130 (15.4%) | 19/120 (15.8%) | ||
| Diarrhea | 41/130 (31.5%) | 51/120 (42.5%) | ||
| Nausea | 123/130 (94.6%) | 120/120 (100%) | ||
| General disorders | ||||
| Fluid overload | 58/130 (44.6%) | 54/120 (45%) | ||
| Elevated transminitis | 106/130 (81.5%) | 120/120 (100%) | ||
| Fevers | 0/130 (0%) | 17/120 (14.2%) | ||
| Hepatobiliary disorders | ||||
| Liver GvHD | 25/130 (19.2%) | 21/120 (17.5%) | ||
| Ascites | 2/130 (1.5%) | 1/120 (0.8%) | ||
| VOD/SOS | 0/130 (0%) | 2/120 (1.7%) | ||
| Immune system disorders | ||||
| Allergic reaction to ATG | 2/130 (1.5%) | 4/120 (3.3%) | ||
| Infections and infestations | ||||
| Infections | 103/130 (79.2%) | 89/120 (74.2%) | ||
| BK virus associated hemorrhagic cystitis | 20/130 (15.4%) | 27/120 (22.5%) | ||
| Investigations | ||||
| ATG induced fevers | 65/130 (50%) | 41/120 (34.2%) | ||
| Neutropenic fevers | 42/130 (32.3%) | 47/120 (39.2%) | ||
| autoimmune hemolytic anemia | 0/130 (0%) | 1/120 (0.8%) | ||
| Nervous system disorders | ||||
| PRES | 1/130 (0.8%) | 3/120 (2.5%) | ||
| Headaches | 10/130 (7.7%) | 13/120 (10.8%) | ||
| Confusions | 0/130 (0%) | 9/120 (7.5%) | ||
| Renal and urinary disorders | ||||
| Renal insufficiency | 28/130 (21.5%) | 25/120 (20.8%) | ||
| Hemorrhagic cystits | 2/130 (1.5%) | 0/120 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Chronic lung GvGHD | 9/130 (6.9%) | 7/120 (5.8%) | ||
| Pneumonitis | 15/130 (11.5%) | 18/120 (15%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Skin GvHD | 71/130 (54.6%) | 83/120 (69.2%) | ||
| Palmar-plantar erythrodysesthesia | 11/130 (8.5%) | 12/120 (10%) | ||
| ATG induced skin rash | 19/130 (14.6%) | 8/120 (6.7%) | ||
| Rash | 14/130 (10.8%) | 18/120 (15%) | ||
| Vascular disorders | ||||
| Hypertension | 38/130 (29.2%) | 37/120 (30.8%) | ||
| Pulmonary embolism | 0/130 (0%) | 1/120 (0.8%) | ||
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 | Richard Champlin, MD / Stem Cell Transplantation |
|---|---|
| Organization | University of Texas MD Anderson Cancer Center |
| Phone | 713-792-3618 |
| rchampli@mdanderson.org |
- 2011-0628
- NCI-2012-00038