Juvenile Myelomonocytic Leukemia
Conditions
Keywords
Stem cell transplant, long term survival, retinoic acid
Brief summary
The investigators hypothesize that long-term disease-free survival (DFS) in patients with JMML can be achieved with a treatment of busulfan (BU), cyclophosphamide (CY) and melphalan (L-PAM) followed by hematopoietic cell transplantation (HCT).
Detailed description
Prior to transplantation, subjects will receive BUSULFAN via the central venous line, six 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 leukemia. As well, these drugs will destroy the subject's own immune system to help ensure the new bone marrow takes and grows after transplantation. On the day of transplantation, bone marrow or umbilical cord blood from the donor will arrive to the bone marrow transplant unit and be transfused via venous line. These new cells will replace the subject's bone marrow.
Interventions
BIOLOGICALStem Cell Transplant
Transplantation on Day 0.
* Busulfan * Cyclophosphamide * Mesna * Melphalan * Anti-thymocyte Globulin (ATG)
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 18 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have a diagnosis of JMML and fulfill these minimal criteria (International diagnostic criteria for JMML): * Leukocytosis (\> 13,000) with absolute monocytosis (\> 1,000) * The presence of immature myeloid cells in the peripheral blood * Less than 30% marrow blasts * Absence of t(9:22) or BCR-ABL transcript * Adequate major organ function including: * Cardiac: ejection fraction \> 45% * Hepatic: no clinical evidence of hepatic failure (e.g. coagulopathy, ascites) * Karnofsky performance status \> 70% or Lansky score \> 50% * Creatinine must be \< 2 x normal for age * Written informed consent.
Exclusion criteria
* Active uncontrolled infection within one week of HCT.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determine Probability of Long-term Disease Free Survival in JMML | at 1 year after transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Combined Incidence of Neutrophil Engraftment, Graft-versus-host Disease (GVHD), Regimen-related Toxicity, and Relapse. | at 1 year after transplant | Measured by AGVHD Grades 2 - 4. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intent-to-Treat Patients receiving study regimen.
Stem Cell Transplant: Transplantation on Day 0.
Preparative Regimen: - Busulfan
* Cyclophosphamide
* Mesna
* Melphalan
* Anti-thymocyte Globulin (ATG) | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Intent-to-Treat |
|---|---|
| Age, Categorical <=18 years | 15 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 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 | 4 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 15 |
| other Total, other adverse events | 15 / 15 |
| serious Total, serious adverse events | 5 / 15 |
Outcome results
Primary
Determine Probability of Long-term Disease Free Survival in JMML
Time frame: at 1 year after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-Treat | Determine Probability of Long-term Disease Free Survival in JMML | 67 Percentage of participants |
Secondary
Combined Incidence of Neutrophil Engraftment, Graft-versus-host Disease (GVHD), Regimen-related Toxicity, and Relapse.
Measured by AGVHD Grades 2 - 4.
Time frame: at 1 year after transplant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Intent-to-Treat | Combined Incidence of Neutrophil Engraftment, Graft-versus-host Disease (GVHD), Regimen-related Toxicity, and Relapse. | 33 Percentage of participants |