Trial Outcomes & Findings for Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells (NCT NCT02512679)
NCT ID: NCT02512679
Last Updated: 2017-02-27
Results Overview
Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20,000 per cubic milimeter (20K) - evaluation by Chimerism Study (STR or FISH) at day +30
TERMINATED
PHASE2
20 participants
30 days
2017-02-27
Participant Flow
Patients for bone marrow transplantation who met the eligibility criteria of diagnosis and clinical status and had histocompatible sibling donor. These patients were recruited at Children's Hospital Los Angeles and Lucille Packard Children's Hospital at Stanford University. Patients were recruited between 2006 and 2013.
This is a sequential dose de-escalation of Cyclophosphamide with first at 105 mg/kg total dose compared to standard 200mg/kg total dose (Arm 1). Prior to enrollment patients had to meet all eligibility criteria for allogeneic transplantation. Study closed after 1st level because all patients engrafted and none had toxicity related to transplant.
Participant milestones
| Measure |
Cyclophosphamide Dose Level 1
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
Cyclophosphamide Dose Level 2
De-escalation of Cyclophosphamide given by Intravenous (IV) at a total dose of 70 mg/kg, to be divided into two doses of one 35 mg/kg dose per day, for 2 days
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 75 mg/kg, to be divided into two doses of one 35 mg/kg dose per day, for 2 days. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
0
|
|
Overall Study
COMPLETED
|
20
|
0
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells
Baseline characteristics by cohort
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Age, Categorical
<=18 years
|
19 Participants
n=99 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=99 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
|
Age, Continuous
|
2.3 years
n=99 Participants
|
|
Gender
Female
|
13 Participants
n=99 Participants
|
|
Gender
Male
|
7 Participants
n=99 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 30 daysPopulation: Subject enrolled and received Dose Level 1 of Cyclophosphamide and engrafted with Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20k - evaluation by Chimerism Study (STR or FISH) at day +30.
Absolute Neutrophil Count (ANC) =/\>500;(recovery of white cell count - self sustain platelet above 20,000 per cubic milimeter (20K) - evaluation by Chimerism Study (STR or FISH) at day +30
Outcome measures
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Number of Participants With Neutrophil Engraftment (=/>500 Cells/uL) and Platelet Engraftment (>20K Cell/uL) at 30 Days
|
20 participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: All subjects who received dose level 1 of Cyclophosphamide did not experience re-occurrence of disease.
assess rate of disease recurrence ("late relapse") due to autologous recovery of recipient hematopoiesis at one year post-HSCT.
Outcome measures
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Number of Participants With Disease Recurrence at 1 Year Post-transplant
|
0 participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: Subjects who received dose level 1 of Cyclophosphamide did not experience veno-occlusive disease, organ failure or severe mucositis.
Assessment of conditioning regimen related toxicity was evaluated and documented with daily assessment during hospitalization and post-transplant follow-up up to one year. None of the subjects developed VOD necessitating any therapeutic intervention, severe mucositis, or toxicity of the Kidney, Liver or Gastrointestinal.
Outcome measures
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant
Veno-Occlusive Disease
|
0 participants
|
|
Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant
Viral Infection
|
8 participants
|
|
Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant
Toxicity of Kidney, Liver, or Gastrointestinal
|
0 participants
|
|
Number of Participants Who Developed Severe Mucositis, Veno-occlusive Disease (VOD), Toxicity of the Kidney, Liver, or Gastrointestinal (GI) Tract up to 1 Year Post-transplant
Severe Mucositis
|
0 participants
|
SECONDARY outcome
Timeframe: 1 yrPopulation: Subjects who received dose level 1 of Cyclophosphamide were revaluated for graft-versus-host disease (GVHD) post transplantation.
Clinical evaluation on a daily basis during hospitalization and at each post transplant clinical visit, up to one year, to determine incidence of acute and chronic graft-versus-host disease using Glucksberg grading scale. Acute graft-versus-host disease (aGVHD) develops within the first three months after transplantation and appears as a skin rash, often accompanied by hyperbilirubenemia, abnormal liver enzymes and gastrointestinal symptoms, as diarrhea, nausea and vomiting. Level of aGVHD is graded from 1-4. Chronic GVHD, typically a late complication of Blood and Marrow Transplantation (BMT) characterized by skin changes, sometimes sclerotic changes, with joint contractures, liver function abnormality, gastrointestinal symptoms and sometime other organ involvement such as eyes, lungs, and obliterative bronchiolitis (OB). Chronic GVHD is graded as absent, limited, or extensive.
Outcome measures
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale
Acute GVHD (Grade 1-2)
|
10 participants
|
|
Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale
Acute GVHD (Grade 3-4)
|
0 participants
|
|
Number of Participants Who Developed Graft-Versus-Host-Disease (GVHD) as Determined by the Glucksberg Scale
Chronic GVHD
|
0 participants
|
SECONDARY outcome
Timeframe: 1 yrPopulation: Subjects receiving dose level 1 of Cyclophosphamide event free survival post transplant at 100 days was 95% and 90% 1 year.
Evaluation for engraftment, correction of the disease, transplant related complications and event-free survival and overall survival of the subjects post-transplant was undertaken by standard measures and evaluation of disease with disease-specific testing.
Outcome measures
| Measure |
Cyclophosphamide Dose Level 1
n=20 Participants
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant
100 Day Event Free Survival Post Transplant
|
19 participants
|
|
Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant
One Year Event Free Survival Post Transplant
|
18 participants
|
|
Number of Participants Who Were Disease Progression-Free and Death-Free at 1 Year Post-transplant
Disease Progression-Free
|
20 participants
|
Adverse Events
Cyclophosphamide Dose Level 1
Serious adverse events
| Measure |
Cyclophosphamide Dose Level 1
n=20 participants at risk
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Death due to pre-exisiting mucormycosis
|
5.0%
1/20 • Number of events 1 • Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure.
|
|
Respiratory, thoracic and mediastinal disorders
Death due to interstitial pneumonia
|
5.0%
1/20 • Number of events 1 • Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure.
|
Other adverse events
| Measure |
Cyclophosphamide Dose Level 1
n=20 participants at risk
Cyclophosphamide given by Intravenous (IV) at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level.
Drug to be given in combination of Busulfan, Campath and Fludarabine
Cyclophosphamide Dose Level 1: given by IV at a total dose of 105 mg/kg, to be divided into three doses of one 35 mg/kg dose per day, for 3 days on the first level. After ten patients the de-escalation will begin if the stopping rule is not met.
|
|---|---|
|
Blood and lymphatic system disorders
Cytomegalovirus (CMV) infection
|
25.0%
5/20 • Number of events 5 • Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure.
|
|
Blood and lymphatic system disorders
Epstein-Barr Virus (EBV)
|
5.0%
1/20 • Number of events 1 • Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure.
|
|
Blood and lymphatic system disorders
Adenovirus
|
5.0%
1/20 • Number of events 1 • Adverse event data was collected throughout the course of the study up to 2 years post transplantation. Subjects were evaluated for post transplant complications related to conditioning, such as VOD, GVHD, infections and engraftment failure.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place