Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome
Conditions
Brief summary
This is a treatment guideline to allow routine clinical data to be collected and maintained in Oncore (clinical database) and the University of Minnesota Blood and Marrow Database as part of the historical database maintained by the department.
Detailed description
This is a single arm trial to evaluate the efficacy of busulfan and cyclophosphamide followed by an allogeneic hematopoietic stem cell transplant (HSCT) in the treatment of hematological malignancies. The intent of this study is to provide a protocol that will use unmanipulated allogeneic hematopoietic stem cells from related and unrelated donors after a common preparative regimen.
Interventions
DRUGAllopurinol
Day -8 (prior to transplant): Per institutional guidelines
DRUGKeppra
Day -8 (prior to transplant): Per institutional guidelines
DRUGBusulfan
Days -7 through -4 (prior to transplant): given intravenously (IV) infusion over 2 hours every 6 hours following dose, administration and pharmacokinetic monitoring per University of Minnesota institutional guidelines.
DRUGCyclophosphamide
Days -3 and -2 (prior to transplantation): given as a 2 hour intravenous infusion with a high volume fluid flush and mesna per institutional guidelines. Dosing is based on actual body weight.
DRUGTacrolimus
All patients (regardless of allograft source) will receive tacrolimus therapy beginning on day -3. Dosing will be monitored and altered as clinically appropriate per institutional pharmacy guidelines. Dose adjustments will be made on the basis of toxicity and/or low tacrolimus levels. Taper at day +100 for matched sibling donor (MSD) recipients, and day +180 for non-MSD recipients. Taper to zero by 10% weekly dose reduction over approximately 10 weeks.
DRUGMycophenolate mofetil
Day -3 (prior to transplant): Recipients of umbilical cord blood will given a dose of 3 gm/day every 8 or 12 hours (\> or = 40 kg) or 15 mg/kg 3 times per day (\< 40 kg) for up to 30 days unless no engraftment.
Day 0 (or Day+1/+2 to accommodate weekdays): Infusion of cells from related or unrelated donor bone marrow or single or double unrelated donor umbilical cord blood.
BIOLOGICALFilgrastim
Beginning Day +1: Intravenously (IV) 5 mcg/kg once daily and continuing until the absolute neutrophil count is \>2500 x 10\^9/L or per institutional guidelines.
BIOLOGICALantithymocyte globulin
Administered per institutional guidelines for recipients of umbilical cord blood transplant.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 44 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and current in complete remission meeting one of the following: * \<45 years of age who are at least 6 months after initial hematopoietic stem cell transplant (HSCT) * \<45 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy * Karnofsky performance status \>70% or if \<16 years of age, a Lansky play score \>50 * Adequate major organ function including: * cardiac: left ventricular ejection fraction \>45% by echocardiogram (ECHO/MUGA) * renal: creatinine clearance \>40 mL/min/1.73m\^2 * hepatic: no clinical evidence of hepatic failure (e.g., coagulopathy, ascites) * An acceptable source of stem cells according to current University of Minnesota Bone Marrow Transplant program guidelines. Acceptable stem cell sources include: * HLA-matched related or unrelated donor bone marrow (6/6 or 5/6 antigen match) * HLA-matched related or unrelated donor peripheral blood stem cells * related or single or double unrelated donor umbilical cord blood (6/6, 5/6 or 4/6 match) * Women of childbearing age must have a negative pregnancy test and all sexually active participants must agree to use effective contraception during study treatment * Written consent (adult or parent/guardian)
Exclusion criteria
* eligible for TBI containing preparative regimen * active uncontrolled infection within one week of study enrollment * pregnant or lactating female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Counts of Participants With Disease Free Survival | 2 Years | The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
| Count of Participants With Disease Free Survival | 5 Years | The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Chronic Graft-Versus-Host Disease | 6 Months | Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. |
| Percentage of Participants With Treatment-Related Toxicity | 6 Months | In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation. |
| Percentage of Participants With Relapse | 1 Year | The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
| Count of Participants Who Achieved Neutrophil Engraftment | By Day 42 | Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm\^3 (0.5 x 10\^9/L) or greater. |
| Number of Participant Who Were Alive at 2 Years Post Transplant | 2 Years | Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive. |
| Number of Participant Who Were Alive at 5 Years Post Transplant | 5 Years | Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive. |
| Number of Participant Who Were Alive at 7 Years Post Transplant | 7 Years | Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive. |
| Percentage of Participants With Engraftment Failure | Day 42 | Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets. |
| Percentage of Participants With Acute Graft-Versus-Host Disease by Grade | Day 100 | Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | Allogeneic Hematopoietic Stem Cell Transplant |
|---|---|
| Age, Categorical <=18 years | 5 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Count of Participants With Disease Free Survival
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 5 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Count of Participants With Disease Free Survival | 1 Participants |
Primary
Count of Participants With Disease Free Survival
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 7 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Count of Participants With Disease Free Survival | 1 Participants |
Primary
Counts of Participants With Disease Free Survival
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Counts of Participants With Disease Free Survival | 3 Participants |
Secondary
Count of Participants Who Achieved Neutrophil Engraftment
Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm\^3 (0.5 x 10\^9/L) or greater.
Time frame: By Day 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Count of Participants Who Achieved Neutrophil Engraftment | 5 Participants |
Secondary
Number of Participant Who Were Alive at 2 Years Post Transplant
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Number of Participant Who Were Alive at 2 Years Post Transplant | 4 Participants |
Secondary
Number of Participant Who Were Alive at 5 Years Post Transplant
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Time frame: 5 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Number of Participant Who Were Alive at 5 Years Post Transplant | 3 Participants |
Secondary
Number of Participant Who Were Alive at 7 Years Post Transplant
Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.
Time frame: 7 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Number of Participant Who Were Alive at 7 Years Post Transplant | 1 Participants |
Secondary
Percentage of Participants With Acute Graft-Versus-Host Disease by Grade
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Time frame: Day 100
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Acute Graft-Versus-Host Disease by Grade | Grade 2-4 | 40 percentage of participants |
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Acute Graft-Versus-Host Disease by Grade | Grade 3-4 | 20 percentage of participants |
Secondary
Percentage of Participants With Chronic Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Chronic Graft-Versus-Host Disease | 0 percentage of participants |
Secondary
Percentage of Participants With Chronic Graft-Versus-Host Disease
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Chronic Graft-Versus-Host Disease | 0 percentage of participants |
Secondary
Percentage of Participants With Engraftment Failure
Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
Time frame: Day 42
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Engraftment Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Relapse
The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 2 Years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Relapse | 40 percentage of participants |
Secondary
Percentage of Participants With Relapse
The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 1 Year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Relapse | 40 percentage of participants |
Secondary
Percentage of Participants With Treatment-Related Toxicity
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Treatment-Related Toxicity | 0 percentage of participants |
Secondary
Percentage of Participants With Treatment-Related Toxicity
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Allogeneic Hematopoietic Stem Cell Transplant | Percentage of Participants With Treatment-Related Toxicity | 0 percentage of participants |