AML, Leukemia, Lymphocytic, Acute, MDS
Conditions
Keywords
Stem Cell transplant, retransplant, hematological malignancies
Brief summary
This protocol using busulfan, cyclophosphamide and melphalan has been designed as conditioning therapy for patients receiving stem cell transplantation for acute leukemia or myelodysplastic syndrome (MDS). The hypothesis is that this new regimen will be well tolerated and will cure the patient.
Detailed description
Subjects will be admitted to the bone marrow transplant unit and put in isolation to reduce exposure to infectious agents. Prior to transplantation, they will receive BUSULFAN via the central venous line, four times a day for four days, CYCLOPHOSPHAMIDE via the central venous line once a day for two days, and MELPHALAN via the central venous line for one day. Busulfan, cyclophosphamide, and melphalan are given to destroy the subject's cancer. As well, these drugs will destroy their immune system to help ensure the new stem cells take and grow after transplantation. On the day of transplantation, umbilical cord blood from the donor will be transfused via venous line. These new cells will replace the subject's bone marrow. After transplantation, the subjects will receive Cyclosporin A and either MMF or MTX Isolation will be continued until adequate numbers of cells are present in the blood to fight infection. Subjects will be discharged from the hospital when medically ready. They will be expected to return for follow-up to the blood and marrow transplant clinic at specific dates as determined by physicians.
Interventions
PROCEDUREStem Cell Transplant
Certain cancers can be treated by giving patients stem cells that come from someone else. This is called a stem-cell transplant. As part of the transplant process, patients receive high doses of chemotherapy and/or radiation to treat their underlying disease, such as cancer. As one of its effects, this treatment also kills the healthy stem cells that are already in the marrow. The transplant provides new stem cells for the patient from a healthy donor; that replace the bone marrow and allow the blood counts to recover.
DRUGBusulfan
Prior to transplantation, subjects will receive BUSULFAN via the central venous line, four times a day for four days (days -7 through -4).
DRUGCyclophosphamide
Prior to stem cell transplantation, subjects will receive CYCLOPHOSPHAMIDE via the central venous line once a day for two days on days -3 and -2.
DRUGMelphalan
MELPHALAN will be given via the central venous line for one day, on day -1, prior to stem cell transplantation.
DRUGG-CSF
G-CSF is to be given daily IV beginning on day +1 until ANC 2.5 x 109/L.
DRUGATG
ATG will be administered to umbilical cord blood recipients.
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 35 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have a diagnosis of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and currently be in complete remission. * Patients must be either: * \- \<18 years of age who are at least 6 months after initial hematopoietic cell transplant (HCT), * \- 19-35 years of age and at least 18 months after initial HCT, or * \- \<35 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy * Adequate major organ function including: * \- Cardiac: ejection fraction \> or = 45% * \- Renal: creatinine clearance \> or = 40 mL/min * \- Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites) * \- Karnofsky performance status \> or = 70% or Lansky score \> or = 50% * Women of child bearing age must be using adequate birth control and have a negative pregnancy test. * Written informed consent.
Exclusion criteria
* Eligible for TBI containing preparative regimen. * Active uncontrolled infection within one week of HCT. * Pregnant or lactating females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Long-term Disease-free Survival (DFS) | 1 year | Number of participants with long-term disease free survival after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Probability of Engraftment | 1 year | Number of participants with engraftment after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.. |
| Incidence of Acute Graft-versus-host Disease (GVHD) | 100 days post-transplant | Number of participants with acute GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. |
| Incidence Chronic Graft-versus-host Disease (GVHD) | 1 year | Number of participants with chronic GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. |
| Incidence of Regimen-related Toxicity 100 Days Post Transplant | 100 days post-transplant | Number of participants with regimen-related toxicity 100 days post transplant after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. |
| Incidence of Relapse | 1 year | Number of patients with relapse after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies. |
Countries
United States
Participant flow
Recruitment details
The study was offered to patients at the time different treatment options were being discussed in the clinic or in the hospital.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Patients treated with therapy plan ((Busulfan, Cyclophosphamide, Melphalan, antithymocyte globulin (ATG), G-CSF (granulocyte colony-stimulating factor) and stem cell transplantation. | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Categorical <=18 years | 9 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 10.3 years STANDARD_DEVIATION 8.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 2 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 10 / 11 |
Outcome results
Primary
Probability of Long-term Disease-free Survival (DFS)
Number of participants with long-term disease free survival after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Probability of Long-term Disease-free Survival (DFS) | 3 participants |
Secondary
Incidence Chronic Graft-versus-host Disease (GVHD)
Number of participants with chronic GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Incidence Chronic Graft-versus-host Disease (GVHD) | 0 participants |
Secondary
Incidence of Acute Graft-versus-host Disease (GVHD)
Number of participants with acute GVHD after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Time frame: 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Incidence of Acute Graft-versus-host Disease (GVHD) | 7 participants |
Secondary
Incidence of Regimen-related Toxicity 100 Days Post Transplant
Number of participants with regimen-related toxicity 100 days post transplant after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Time frame: 100 days post-transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Incidence of Regimen-related Toxicity 100 Days Post Transplant | 3 participants |
Secondary
Incidence of Relapse
Number of patients with relapse after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies.
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Incidence of Relapse | 2 participants |
Secondary
Probability of Engraftment
Number of participants with engraftment after being treated with busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by HCT for hematological malignancies..
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Probability of Engraftment | 10 participants |