Graft-versus-host Disease, Mucositis
Conditions
Keywords
Tacrolimus, Methotrexate, Mycophenolate mofetil, Mucositis, Acute graft-versus-host disease (aGVHD), Engraftment, hemolytic/uremic syndrome (HUS), Thrombotic thrombocytopenic purpura (TTP)
Brief summary
A comparative trial where all patients will receive daily doses of tacrolimus (TAC) until day +60 when tapering will begin, in the absence of graft-versus-host disease (GVHD), and discontinued by day +180. In addition patients will be randomized to methotrexate (MTX) or mycophenolate mofetil (MMF) and again, in the absence of GVHD, a tapering schedule will begin on day +240 and be completed on day +360. Doses will be adjusted to maintain blood levels.
Detailed description
The randomization for this comparative trial will be stratified by conditioning regimen and, for those patients enrolled on MCC-14178, by busulfan AUC level. All patients will receive daily doses of TAC beginning day -3 (day 0 being the day of hematopoietic stem cell transplant (HCT)) and will be given until day +60 when tapering will begin in the absence of GVHD. Provided no GVHD develops, TAC should be discontinued by day +180. Doses will be adjusted to maintain blood levels. In addition to TAC, patients will be randomized to one of the following additional anti-GVHD medications: MTX or MMF beginning day 0 at least 2 hours after the end of the HCT. In the absence of GVHD a tapering schedule will begin on day +240 and be completed on day +360. Study participants will be extensively monitored as inpatients and then weekly as outpatients. Some tests will be conducted at least twice weekly (blood tests, toxicity data, GVHD and physical exams) one-month post-transplant and during the tapering off periods for up to 2 years.
Interventions
DRUGTac+MTX
Tacrolimus- 0.03mg/kg/24h IV beginning day-3 Methotrexate- 15mg/m2 IV day +1 then 10mg/m2 IV on days 3, 6, 11 post transplant.
DRUGTAC + MMF
Tacrolimus- 0.03 mg/kg/24h as a continuous IV infusion, beginning day -3. Mycophenolate Mofetil- 30 mg/kg/day IV in 2 divided doses (q12 hours) beginning day 0 at least 2 hours after the end of the hematopoietic stem cell transplant
Sponsors
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
\- Patient must be going through a T cell-replete allogeneic transplant
Exclusion criteria
\- A contraindication to the use of tacrolimus, mycophenolate, or methotrexate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Severe Mucositis | 2 year | Mucositis was assessed prospectively daily while the patient was hospitalized and graded retrospectively based on nurse and clinician assessments according to the clinical criteria set forth in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). Severe mucositis as defined as grade 3 or grade 4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Acute Graft-vs-host Disease (aGVHD) | 100 days post transplant | incidence of aGVHD (grades 2 - 4) 100 days post allogeneic hematopoietic cell transplantation |
| Overall Survival | 1 year | number of participants alive at one year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tacrolimus And Methotrexate Tacrolimus (TAC) And Methotrexate (MTX) | 47 |
| Tacrolimus And Mycophenolate Mofetil Tacrolimus (TAC) And Mycophenolate Mofetil (MMF) | 42 |
| Total | 89 |
Baseline characteristics
| Characteristic | Tacrolimus And Methotrexate | Tacrolimus And Mycophenolate Mofetil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 39 Participants | 84 Participants |
| Region of Enrollment United States | 47 participants | 42 participants | 89 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 39 Participants |
| Sex: Female, Male Male | 29 Participants | 21 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 47 | 0 / 42 |
| serious Total, serious adverse events | 25 / 47 | 19 / 42 |
Outcome results
Primary
Incidence of Severe Mucositis
Mucositis was assessed prospectively daily while the patient was hospitalized and graded retrospectively based on nurse and clinician assessments according to the clinical criteria set forth in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 3.0). Severe mucositis as defined as grade 3 or grade 4.
Time frame: 2 year
Population: Intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus And Methotrexate | Incidence of Severe Mucositis | 25 participants |
| Tacrolimus And Mycophenolate Mofetil | Incidence of Severe Mucositis | 14 participants |
Comparison: Sample size was based on the difference in the proportion of patients in each arm who were predicted to develop severe mucositis defined as clinical grade 3 or 4 per the CTCAE. A sample-size of 42 evaluable subjects per study-arm allowed detection of an absolute difference of 30%, which corresponds to a reduction in the incidence of severe mucositis from 60% in the methotrexate arm to 30% in the MMF arm (alpha=0.05, power=0.80).p-value: 0.06Fisher Exact
Secondary
Incidence of Acute Graft-vs-host Disease (aGVHD)
incidence of aGVHD (grades 2 - 4) 100 days post allogeneic hematopoietic cell transplantation
Time frame: 100 days post transplant
Population: intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus And Methotrexate | Incidence of Acute Graft-vs-host Disease (aGVHD) | 45 participants |
| Tacrolimus And Mycophenolate Mofetil | Incidence of Acute Graft-vs-host Disease (aGVHD) | 33 participants |
p-value: 0.8K-sample tests for comparing the cumulat
Secondary
Overall Survival
number of participants alive at one year
Time frame: 1 year
Population: intent to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tacrolimus And Methotrexate | Overall Survival | 28 participants |
| Tacrolimus And Mycophenolate Mofetil | Overall Survival | 27 participants |
p-value: 0.58Log Rank