Allogeneic Stem Cell Transplantation, Severe Homzygous 0/+Thalassemia or Sever Variants of Beta 0/+ Thalassemia, THALLO
Study Details
Study Description
Brief Summary
Patients have severe beta-thalassemia or one of the thalassemia variants. Thalassemia is a hereditary disease in which the bone marrow produces abnormal red blood cells that have a shorter life span than normal red blood cells. Because of that, the patient has chronically low red blood cell numbers (anemia) and need regular blood transfusions to help the patient feel better and to help prevent damage to important organs such as the heart. The following treatments are currently available to patients: lifelong blood transfusions and drugs that help remove iron from the body, and long-term antibiotics to prevent infections. These treatments are difficult for patients to take, and do not stop the effects of the disease.
Currently, the only treatment that may cure thalassemia is bone marrow or blood stem cell transplantation. Special blood or bone marrow cells from a healthy person might allow the bone marrow to create healthy cells, which will replace the abnormal red blood cells of thalassemia. There is a lot of experience using special blood or bone marrow cells from a healthy brother or sister who is the same HLA (immune) type. For patients who do not have such a donor in the family, an unrelated volunteer donor can be used. It is important for the patient to realize that this kind of transplant can have more problems than a transplant from a brother or sister.
Because we do not know the long-term effects of this treatment and because this type of transplant has not been used often for people with thalassemia, this is a research study. We hope, but cannot promise, that the transplanted marrow/stem cells will produce healthy cells and the patient will no longer have severe thalassemia.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
To be treated on this study, we will test the blood to check for viruses, including HIV (the virus that causes AIDS). If the HIV test is positive, a transplant cannot be done because it would be too dangerous for the patient. Secondly, we will do a liver biopsy to determine if the liver has been damaged (which can happen from iron overload that develops after many transfusions). Too much liver damage could mean that the patient will have a higher risk to develop problems with the transplant.
To participate in this study, the patients also need to have a central line (a thin plastic catheter or tube that is placed during surgery into one of the large veins in the neck or chest). Central lines are used to give intravenous medications (go directly into the vein) or to take blood samples without the patient having to endure frequent needle sticks. Before the treatment starts, we will remove a small amount of the bone marrow (back-up bone marrow) and store it. The reason for this is that if the donors bone marrow or blood stem cells do not grow properly after the transplant and the patients blood counts stay low, we can put the patients own bone marrow cells back into their body. This will help the blood counts to recover, but this means that the patient will also have thalassemia again.
To prepare the body for the transplant, the patients own blood forming system has to be destroyed and their immune system has to be weakened. To do this, they will be given high dose chemotherapy and medications that weaken their immune system (also called a conditioning treatment) for 9 days before the transplant. The main chemotherapy drugs used in the conditioning treatment are: cyclophosphamide, fludarabine and busulfan. The chemotherapy treatment will last 9 days. The patient will be admitted 10 days before the transplant to start a medicine to prevent seizures before they receive the first dose of busulfan since one of the side effects of busulfan is risk of seizures. First the patient will be given a drug called busulfan through the central line every 6 hours starting 9 days before transplant (called Day -9) until 6 days before transplant (called Day -6). Starting one day after receiving the last busulfan dose (Day -5), they will receive cyclophosphamide, fludarabine and Campath IH, which will all be given through the central line once a day for the next four days. Campath IH is a special type of protein called an antibody that works against certain types of blood cells. Also on Day -5, we will add a drug called MESNA. MESNA is used to decrease the side-effects caused by cyclophosphamide.
One day after the chemotherapy treatment is finished (Say -1) the patient will have a day to rest. On Say 0, the patient will receive the bone marrow/stem cells from the donor. Once in the bloodstream, the cells will go to the bone marrow and should begin to grow. To help prevent a problem call graft-versus-host disease (GVHD), the patient will receive a small dose of methotrexate on four different days after transplant. Another drug to help prevent GVHD, tacrolimus, will be started 2 days (Day -2) before the transplant and continued for approximately one year after the transplant. To tell whether the transplant has "taken" or "engrafted", we will take samples of blood two to three weeks after the transplant.
The patient will need to be in the hospital for at least 4 weeks after the transplant to make sure the transplant has engrafted. To find out how much the treatment has helped them and how much it might help other patients, we will do several routine lung, kidney, and liver tests, including liver biopsies, after the bone marrow/stem cell transplant. Additionally, we will be looking at the immune function. To do this, we will take 30 mL (2 tablespoonfuls) of blood every three months for the first year after transplant and then every 6 months during the second year after transplant. When possible, the blood that is taken will be taken through an existing IV line. However, at times drawing the blood will require another stick with a needle. The total amount of blood to be taken will not exceed 12 tablespoonfuls.
Because bone marrow/stem cell transplant from an unrelated volunteer donor is a new therapy for severe thalassemia and because problems may happen months afterward, the patient will need to have exams and blood tests done every few months during the first and second year following transplantation.
The patient may still need to use iron removing agents for some time after transplant or undergo blood-letting to get rid of the excess iron in the body. During that time, we will monitor the amount of iron in the body. Looking at the iron stored in the liver can most accurately tell us how much excess iron the patient has in the body. We will do liver biopsies once or twice per year if the patient is receiving iron chelation treatment after the transplant.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Bone Marrow or Stem Cell Infusion Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. |
Drug: Busulfan
4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg
Days -9 through -6
Other Names:
Drug: Fludarabine
30mg/m2 Day -5 through Day -2
Other Names:
Drug: Campath 1H
Per institutional guidelines Days -5 through -2
Other Names:
Drug: Cyclophosphamide
50 mg/kg Days -5 through -2
Other Names:
Drug: MESNA
10 mg/kg x 5 Days -5 through -2
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Engraftment Rate After Transplant [up to 30 days]
Engraftment is defined as an absolute neutrophil count (ANC) >500/microL x 3 days.
- Number of Participants With Stable Mixed Hematopoietic Chimerism (HC) [1 year post-transplant]
Stable hematopoietic chimerism is defined as having 50-99 percent of donor cells.
- Number of Participants With Transient Mixed Hematopoietic Chimerism (HC) [1 year post-transplant]
Transient mixed hematopoietic chimerism is defined as any mixed chimerism return to 100 percent donor.
- Number of Participants With Infectious Complications [up to day 100]
All AEs and SAEs (including infections) will be collected for evaluation of infectious complications.
- Hematopoietic Reconstitution [1 year post-transplant]
Hematopoietic: defined as transfusion independence.
- Immune Reconstitution [1 year post-transplant]
Immune reconstitution: defined as absolute lymphocyte count (ALC) >1000x10e3/microL
- Number of Participants With ACUTE GVHD [Assessed weekly from Day 0 to day 100]
Acute GVHD is graded by the method of Przepiorka D. et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD
- Number of Participants With CHRONIC GVHD [Assessed monthly from month 3 to month 12]
Chronic GVHD is graded by NIH guidelines for chronic GVHD, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3 where 0 means no chronic GVHD, and 3 is the highest stage of chronic GVHD.
- Event-free Survival [up to 2 years post transplant]
Event-free survival is calculated from the date of transplant to the date of graft failure, disease recurrence or death from any cause.
Eligibility Criteria
Criteria
Inclusion Criteria:
Patients with documented diagnosis of severe (transfusion-dependent) homozygous b0/+-thalassemia or severe variants of b0/+-thalassemia requiring chronic transfusion therapy and iron chelating agents, who fulfill the following conditions:
-
Patient does not have an HLA genotype-identical donor available and has a 5/6 or 6/6 matched unrelated donor, or a 5/6 matched related donor available.
-
Must be between 1 and 16 yrs of age (all Pesaro risk groups).
-
Patients older than 17 yrs of age must be in Pesaro Risk Class 2 or lower (see Appendix B).
-
Women of childbearing potential must have a negative pregnancy test.
-
Documentation of compliance with iron chelation, absence or presence of hepatomegaly, and presence or absence of hepatic fibrosis prior to transplant (criteria for the Pesaro Risk Classification). This information will be obtained by history, physical exam and interpretation of liver biopsy results.
-
Documentation of awareness of alternative treatment options.
Exclusion Criteria:
-
Biopsy-proven chronic active hepatitis or fibrosis with portal bridging.
-
Has previous history of malignancies.
-
Creatinine clearance < 35 mL/min/1.73 M2.
-
Severe cardiac dysfunction defined as shortening fraction < 25%.
-
HIV infection.
-
Inadequate intellectual capacity to give informed consent (in the case of minors, this criteria must be fulfilled by the legal guardian).
-
Be pregnant, lactating or unwilling to use appropriate birth control.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Texas Children's Hospital | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- Baylor College of Medicine
Investigators
- Principal Investigator: Tami John, MD, Baylor College of Medicine - Texas Children's Hospital
- Study Director: Tami John, MD, Baylor College of Medicine - Texas Children's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- THALLO (H-14539)
- H-14539
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Period Title: Overall Study | |
| STARTED | 10 |
| COMPLETED | 7 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Overall Participants | 10 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
6
|
| Sex: Female, Male (Count of Participants) | |
| Female |
5
50%
|
| Male |
5
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
1
10%
|
| Not Hispanic or Latino |
9
90%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
7
70%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
0
0%
|
| White |
3
30%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
Outcome Measures
| Title | Engraftment Rate After Transplant |
|---|---|
| Description | Engraftment is defined as an absolute neutrophil count (ANC) >500/microL x 3 days. |
| Time Frame | up to 30 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) from unrelated donors. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 10 |
| Number (95% Confidence Interval) [proportion of participants] |
1
10%
|
| Title | Number of Participants With Stable Mixed Hematopoietic Chimerism (HC) |
|---|---|
| Description | Stable hematopoietic chimerism is defined as having 50-99 percent of donor cells. |
| Time Frame | 1 year post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) from unrelated donors and had mixed chimerism (MC). Six participants were not evaluable at the time point of assessment for this outcome measure due to death or graft failure or full donor. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 4 |
| Count of Participants [Participants] |
3
30%
|
| Title | Number of Participants With Transient Mixed Hematopoietic Chimerism (HC) |
|---|---|
| Description | Transient mixed hematopoietic chimerism is defined as any mixed chimerism return to 100 percent donor. |
| Time Frame | 1 year post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) from unrelated donors and had mixed chimerism (MC). Six participants were not evaluable at the time point of assessment for this outcome measure due to death or graft failure or full donor. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 4 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Participants With Infectious Complications |
|---|---|
| Description | All AEs and SAEs (including infections) will be collected for evaluation of infectious complications. |
| Time Frame | up to day 100 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) from unrelated donors. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 10 |
| Count of Participants [Participants] |
7
70%
|
| Title | Hematopoietic Reconstitution |
|---|---|
| Description | Hematopoietic: defined as transfusion independence. |
| Time Frame | 1 year post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) and were evaluable for the outcome measure. Two participants were not evaluated at the time point of assessment for this outcome measure due to death or graft failure. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 8 |
| Count of Participants [Participants] |
7
70%
|
| Title | Immune Reconstitution |
|---|---|
| Description | Immune reconstitution: defined as absolute lymphocyte count (ALC) >1000x10e3/microL |
| Time Frame | 1 year post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) and were evaluable for the outcome measure. Two participants were not evaluated at the time point of assessment for this outcome measure due to death or graft failure. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 8 |
| Count of Participants [Participants] |
8
80%
|
| Title | Number of Participants With ACUTE GVHD |
|---|---|
| Description | Acute GVHD is graded by the method of Przepiorka D. et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD |
| Time Frame | Assessed weekly from Day 0 to day 100 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) and were evaluable for acute GVHD. A participant is evaluable for acute GVHD if he/she engrafted and either completed 100 days observation after transplant or experienced acute GVHD. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 10 |
| Grade 0 |
4
40%
|
| Grade I |
4
40%
|
| Grade II-IV |
2
20%
|
| Title | Number of Participants With CHRONIC GVHD |
|---|---|
| Description | Chronic GVHD is graded by NIH guidelines for chronic GVHD, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3 where 0 means no chronic GVHD, and 3 is the highest stage of chronic GVHD. |
| Time Frame | Assessed monthly from month 3 to month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) and were evaluable for chronic GVHD. A participant is evaluable for chronic GVHD if he/she engrafted and survived or remained in the study for more than 100 days after transplant. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 8 |
| Count of Participants [Participants] |
1
10%
|
| Title | Event-free Survival |
|---|---|
| Description | Event-free survival is calculated from the date of transplant to the date of graft failure, disease recurrence or death from any cause. |
| Time Frame | up to 2 years post transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis included all participants who underwent allogeneic hematopoietic stem cell transplantation (SCT) from unrelated donors. |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion |
|---|---|
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 |
| Measure Participants | 10 |
| Number (95% Confidence Interval) [probability of event-free survival] |
0.7
|
Adverse Events
| Time Frame | Primary BMT studies have a critical toxicity period of 30 days after BMT day 0. During the critical toxicity period the most severe grade of all AE's is captured. Grade 1 and 2 AEs, hematological toxicities, and fevers are excluded. Serious Adverse Events/Unanticipated Problems are reported (excluding hematological toxicities and fevers) until 100 days after BMT day 0. | |
|---|---|---|
| Adverse Event Reporting Description | All adverse events were collected using CTCAE 2.0 for the study. For reporting purpose, adverse event terms were converted using CTCAE v4.0. | |
| Arm/Group Title | Bone Marrow or Stem Cell Infusion | |
| Arm/Group Description | Mesna, Cyclophosphamide, Busulfan, Fludarabine, Campath 1H Bone Marrow or Stem Cell infusion with pre-meds to take place on Day 0. Bone marrow dose/stem cell dose: To ensure the probability for bone marrow engraftment, 4 x 10e8 nucleated cells/kg patient weight or 5 x 10e6/kg of CD34+ cells/kg patient weight if the product is mobilized peripheral blood, will be the target to be obtained from the unrelated donor. Busulfan: 4.0 mg/kg/day divided into four doses daily for four days; total dose = 16 mg/kg Days -9 through -6 Fludarabine: 30mg/m2 Day -5 through Day -2 Campath 1H: Per institutional guidelines Days -5 through -2 Cyclophosphamide: 50 mg/kg Days -5 through -2 MESNA: 10 mg/kg x 5 Days -5 through -2 | |
All Cause Mortality |
||
| Bone Marrow or Stem Cell Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | 1/10 (10%) | |
Serious Adverse Events |
||
| Bone Marrow or Stem Cell Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | 4/10 (40%) | |
| Gastrointestinal disorders | ||
| Diarrhea | 1/10 (10%) | 1 |
| Infections and infestations | ||
| Catheter related Infection | 1/10 (10%) | 1 |
| Investigations | ||
| Aspartate aminotransferase increased | 1/10 (10%) | 1 |
| Alanine aminotransferase increased | 2/10 (20%) | 2 |
| Renal and urinary disorders | ||
| Hematuria | 1/10 (10%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Bone Marrow or Stem Cell Infusion | ||
| Affected / at Risk (%) | # Events | |
| Total | 9/10 (90%) | |
| Cardiac disorders | ||
| Cardiac disorders-Other: Cardiomegaly | 1/10 (10%) | 1 |
| Sinus tachycardia | 1/10 (10%) | 1 |
| Eye disorders | ||
| Eye disorders -Other: PRES | 1/10 (10%) | 1 |
| Gastrointestinal disorders | ||
| Abdominal Pain | 2/10 (20%) | 3 |
| Ascites | 1/10 (10%) | 1 |
| Diarrhea | 2/10 (20%) | 3 |
| Gastric ulcer | 1/10 (10%) | 1 |
| Gastritis | 1/10 (10%) | 1 |
| Anal hemorrhage | 2/10 (20%) | 2 |
| Nausea | 1/10 (10%) | 1 |
| Stomatitis/Pharyngitis (oral/pharyngeal mucositis) | 2/10 (20%) | 2 |
| Vomiting | 1/10 (10%) | 2 |
| General disorders | ||
| Pain | 1/10 (10%) | 3 |
| Pelvic Pain | 1/10 (10%) | 1 |
| Hepatobiliary disorders | ||
| Hepatobiliary disorders-Other: GVHD | 1/10 (10%) | 1 |
| Hepatobiliary disorders-Other: hepatic VOD | 1/10 (10%) | 1 |
| Infections and infestations | ||
| Catheter Related Infection | 3/10 (30%) | 3 |
| Infections and infestations - Other: Parainfluenza virus | 1/10 (10%) | 1 |
| Infections and infestations - Other: CMV reactivation | 1/10 (10%) | 1 |
| Infections and infestations - Other: Gram negative rods | 2/10 (20%) | 3 |
| Infections and infestations - Other: BK virus | 3/10 (30%) | 4 |
| Infections and infestations - Other: HSV | 1/10 (10%) | 1 |
| Wound-Infectious | 1/10 (10%) | 1 |
| Investigations | ||
| Blood bilirubin increased | 4/10 (40%) | 6 |
| GGT increased | 5/10 (50%) | 20 |
| Lipase | 1/10 (10%) | 1 |
| Partial thromboplastin time (PTT) | 1/10 (10%) | 1 |
| Prothrombin time (PT) | 2/10 (20%) | 3 |
| Aspartate aminotransferase increased | 8/10 (80%) | 31 |
| Alanine aminotransferase increased | 6/10 (60%) | 31 |
| Metabolism and nutrition disorders | ||
| Acidosis | 1/10 (10%) | 2 |
| Alkalosis | 1/10 (10%) | 1 |
| Anorexia | 1/10 (10%) | 1 |
| Hyperkalemia | 2/10 (20%) | 4 |
| Hypermagnesemia | 2/10 (20%) | 2 |
| Hypertriglyceridemia | 5/10 (50%) | 11 |
| Hypoalbuminemia | 6/10 (60%) | 30 |
| Hypocalcemia | 1/10 (10%) | 1 |
| Hypokalemia | 3/10 (30%) | 10 |
| Hypomagnesemia | 1/10 (10%) | 1 |
| Hyponatremia | 3/10 (30%) | 3 |
| Hypophosphatemia | 3/10 (30%) | 3 |
| Nervous system disorders | ||
| Headache | 1/10 (10%) | 1 |
| Nervous system disorders-Other: Altered mental status | 1/10 (10%) | 1 |
| Psychiatric disorders | ||
| Hallucinations | 2/10 (20%) | 2 |
| Renal and urinary disorders | ||
| Dysuria (painful urination) | 3/10 (30%) | 3 |
| Hematuria | 2/10 (20%) | 2 |
| Hemoglobinuria | 2/10 (20%) | 2 |
| Cystitis noninfective | 1/10 (10%) | 1 |
| Proteinuria | 4/10 (40%) | 10 |
| Renal Failure | 1/10 (10%) | 1 |
| Renal and urinary disorders-Other: Nitrite in urine | 1/10 (10%) | 1 |
| Urine discoloration | 1/10 (10%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||
| Epistaxis | 1/10 (10%) | 1 |
| Hypoxia | 1/10 (10%) | 2 |
| Pleural Effusion | 1/10 (10%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Rash | 1/10 (10%) | 1 |
| Rash | 2/10 (20%) | 3 |
| Vascular disorders | ||
| Hypertension | 3/10 (30%) | 3 |
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. Tami D. John |
|---|---|
| Organization | Baylor College of Medicine/Texas Children's Hospital |
| Phone | 832-824-4723 |
| tdjohn@texaschildrens.org |
- THALLO (H-14539)
- H-14539