Trial Outcomes & Findings for Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer (NCT NCT00089011)

NCT ID: NCT00089011

Last Updated: 2020-01-29

Results Overview

Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

150 participants

Primary outcome timeframe

Day 180 post-transplantation

Results posted on

2020-01-29

Participant Flow

Participant milestones

Participant milestones
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Overall Study
STARTED
100
50
Overall Study
COMPLETED
100
50
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Tacrolimus and Mycophenolate Mofetil in Preventing Graft-Versus-Host Disease in Patients Who Have Undergone Total-Body Irradiation With or Without Fludarabine Phosphate Followed by Donor Peripheral Blood Stem Cell Transplant for Hematologic Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Total
n=150 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
74 Participants
n=5 Participants
49 Participants
n=7 Participants
123 Participants
n=5 Participants
Age, Categorical
>=65 years
26 Participants
n=5 Participants
1 Participants
n=7 Participants
27 Participants
n=5 Participants
Sex: Female, Male
Female
46 Participants
n=5 Participants
17 Participants
n=7 Participants
63 Participants
n=5 Participants
Sex: Female, Male
Male
54 Participants
n=5 Participants
33 Participants
n=7 Participants
87 Participants
n=5 Participants
Region of Enrollment
United States
98 participants
n=5 Participants
46 participants
n=7 Participants
144 participants
n=5 Participants
Region of Enrollment
Italy
2 participants
n=5 Participants
4 participants
n=7 Participants
6 participants
n=5 Participants

PRIMARY outcome

Timeframe: Day 180 post-transplantation

Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Incidence of Grade III/IV GVHD
2 Participants
4 Participants

PRIMARY outcome

Timeframe: Day 180 post-transplantation

Number of patients who developed chronic extensive GVHD post-transplant. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Incidence of Chronic Extensive GVHD
15 Participants
6 Participants

SECONDARY outcome

Timeframe: Day 180 post-transplantation

Number of patients who rejected their graft. Rejection is defined as the inability to detect or loss of detection of greater than 5% donor T cells (CD3+) as a proportion of the total T cell population, respectively, after nonmyeloablative HCT.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Incidences of Graft Rejection
0 Participants
0 Participants

SECONDARY outcome

Timeframe: At 1 year after conditioning

Number of patients surviving post-transplant.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Overall Survival
85 Participants
39 Participants

SECONDARY outcome

Timeframe: Day 180 post-transplantation

Number of patients who developed acute/chronic GVHD post-transplant. aGVHD Stages Skin: a maculopapular eruption involving \< 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 3 skin and/or stage 1 gut involvement and/or stage 1 liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Incidences of Grades II-IV Acute GVHD
26 Participants
14 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Relapse/Progression criteria: CML New cytogenetic abnormality and/or development of accelerated phase or blast crisis. The criteria for accelerated phase will be defined as unexplained fever \>38.3°C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, marrow blasts and promyelocytes \>20%. CMML, AML, ALL \>30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL ≥1 of: Physical exam/imaging studies ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL \>25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ treatment; or definite increase in the size or number of plasmacytomas or lytic bone lesions.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Rates of Disease Progression
41 Participants
33 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Number of patients who expired with relapsed/progressive disease.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Rates of Relapse-related Mortality
28 Participants
23 Participants

SECONDARY outcome

Timeframe: Up to 5 years

Population: Only those patients who received steroids for treatment of chronic GVHD.

Number of patients that received prednisone treatment of chronic GVHD, and number of days for which they received prednisone.

Outcome measures

Outcome measures
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=44 Participants
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=21 Participants
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Rate and Duration of Steroid Use for the Treatment of Chronic GVHD
78 days
Interval 1.0 to 1156.0
89 days
Interval 1.0 to 420.0

Adverse Events

Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)

Serious events: 8 serious events
Other events: 28 other events
Deaths: 0 deaths

Arm II (Nonmyeloablative Conditioning With TBI)

Serious events: 5 serious events
Other events: 17 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 participants at risk
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 participants at risk
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Cardiac disorders
Death, Renal Failure, Cardiac Failure
1.0%
1/100
0.00%
0/50
Immune system disorders
Death due to severe refractory autoimmune hemolytic anemia (present prior to transplant)
1.0%
1/100
0.00%
0/50
Hepatobiliary disorders
Death, elevated bilirubin, fevers
1.0%
1/100
0.00%
0/50
Eye disorders
Right central artery occlusion with right eye blindness
1.0%
1/100
0.00%
0/50
Immune system disorders
Severe abdominal pain due to gut GVHD and supravantricular arrhythmia/Atrial fibrillation
1.0%
1/100
0.00%
0/50
Psychiatric disorders
Mental Status Change while on ativan, oxycodone, and flexeril
1.0%
1/100
0.00%
0/50
Infections and infestations
Sepsis
1.0%
1/100
0.00%
0/50
Hepatobiliary disorders
Elevated LFT's with rising total bilirubin level
1.0%
1/100
0.00%
0/50
Vascular disorders
Hypoxia and Hypotension
0.00%
0/100
2.0%
1/50
Infections and infestations
Death, secondary to sepsis with multiorgan failure
0.00%
0/100
2.0%
1/50
Gastrointestinal disorders
Perforated gastric ulcer
0.00%
0/100
2.0%
1/50
Infections and infestations
Death due to adenovirus nephritis, sepsis, multifactorial renal failure
0.00%
0/100
2.0%
1/50
Renal and urinary disorders
Elevated creatinine level
0.00%
0/100
2.0%
1/50

Other adverse events

Other adverse events
Measure
Arm I (Nonmyeloablative Conditioning With Fludarabine and TBI)
n=100 participants at risk
Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. fludarabine phosphate: Given IV total-body irradiation: Undergo radiotherapy laboratory biomarker analysis: Correlative studies
Arm II (Nonmyeloablative Conditioning With TBI)
n=50 participants at risk
Patients undergo TBI on day 0. All patients then undergo allogeneic peripheral blood stem cell transplantation on day 0 and receive tacrolimus PO every 12 hours on days -3 to 180, with taper on day 56, or tacrolimus IV if unable to tolerate PO; and mycophenolate mofetil PO every 12 hours on days 0-27 or mycophenolate mofetil IV if unable to tolerate PO. total-body irradiation: Undergo radiotherapy mycophenolate mofetil: Given IV or PO tacrolimus: Given IV or PO peripheral blood stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo allogeneic peripheral blood stem cell transplant laboratory biomarker analysis: Correlative studies
Renal and urinary disorders
Increased Creatinine
20.0%
20/100
30.0%
15/50
Blood and lymphatic system disorders
Hemolysis / Hemolytic Anemia
5.0%
5/100
2.0%
1/50
Hepatobiliary disorders
Hyperbilirubinemia
8.0%
8/100
6.0%
3/50
Respiratory, thoracic and mediastinal disorders
Hypoxia / Hypoxemia
5.0%
5/100
4.0%
2/50
Cardiac disorders
Hypotension
1.0%
1/100
8.0%
4/50

Additional Information

David G Maloney, MD PhD

Fred Hutch

Phone: (206) 667-5616

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place