Trial Outcomes & Findings for Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial (NCT NCT01445821)
NCT ID: NCT01445821
Last Updated: 2020-07-23
Results Overview
Treatment failure will not occur until a minimum of 12 months after treatment at which time failure is defined as: 1. Increase of skin score (if \> 14 on enrollment) by \> 25% above enrollment value and must be documented on 2 occasions at least 6 months apart 2. Deterioration in percent predicted FVC by 10% below enrollment level, due to systemic sclerosis, and documented on 2 occasion at least 6 months apart
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
44 participants
Primary outcome timeframe
up to and post 12 months of treatment
Results posted on
2020-07-23
Participant Flow
Participant milestones
| Measure |
Cyclophosphamide rATG/HSCT
Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells
|
Cyclophosphamide rATG/Fludarabine/HSCT
Conditioning regimen will be 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes/stem cells
Fludarabine: Purine analog which inhibits DNA synthesis/repair
|
|---|---|---|
|
Overall Study
STARTED
|
22
|
22
|
|
Overall Study
COMPLETED
|
22
|
22
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Autologous Stem Cell Systemic Sclerosis Immune Suppression Trial
Baseline characteristics by cohort
| Measure |
Cyclophosphamide rATG/HSCT
n=22 Participants
Conditioning regimen: 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: An alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells
|
Cyclophosphamide rATG/Fludarabine/HSCT
n=22 Participants
Conditioning regimen: 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells
Fludarabine: Purine analog which inhibits DNA synthesis/repair
|
Total
n=44 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
22 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
44 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Continuous
|
42.8 years
n=93 Participants
|
45.6 years
n=4 Participants
|
44.2 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=93 Participants
|
4 Participants
n=4 Participants
|
10 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
20 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
37 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
22 participants
n=93 Participants
|
22 participants
n=4 Participants
|
44 participants
n=27 Participants
|
|
Skin Score Prior to Treatment
|
26.1 units on a scale
n=93 Participants
|
22.8 units on a scale
n=4 Participants
|
24.14 units on a scale
n=27 Participants
|
PRIMARY outcome
Timeframe: up to and post 12 months of treatmentTreatment failure will not occur until a minimum of 12 months after treatment at which time failure is defined as: 1. Increase of skin score (if \> 14 on enrollment) by \> 25% above enrollment value and must be documented on 2 occasions at least 6 months apart 2. Deterioration in percent predicted FVC by 10% below enrollment level, due to systemic sclerosis, and documented on 2 occasion at least 6 months apart
Outcome measures
| Measure |
Cyclophosphamide rATG/HSCT
n=17 Participants
Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells
|
Cyclophosphamide rATG/Fludarabine/HSCT
n=15 Participants
Conditioning regimen will be 120 mg/kg of intravenous cyclophosphamide given in 2 equal fractions on days -3 and -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. PBSC will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA
Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Methylpredni
|
|---|---|---|
|
Number of Participants With Treatment Failure
|
2 Participants
|
2 Participants
|
SECONDARY outcome
Timeframe: up to 12 months post treatmentSurvival of Hematopoietic Stem Cell Transplant.
Outcome measures
| Measure |
Cyclophosphamide rATG/HSCT
n=22 Participants
Conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF); a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells
|
Cyclophosphamide rATG/Fludarabine/HSCT
n=22 Participants
Conditioning regimen will be 120 mg/kg of intravenous cyclophosphamide given in 2 equal fractions on days -3 and -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. PBSC will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA
Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonly found on the surface of T cells
Methylpredni
|
|---|---|---|
|
Survival of Treatment
|
22 Participants
|
21 Participants
|
Adverse Events
Cyclophosphamide rATG/HSCT
Serious events: 2 serious events
Other events: 3 other events
Deaths: 2 deaths
Cyclophosphamide rATG/Fludarabine/HSCT
Serious events: 3 serious events
Other events: 2 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Cyclophosphamide rATG/HSCT
n=22 participants at risk
Control arm will have the same conditioning regimen used in ASSIST study. The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA
Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonl
|
Cyclophosphamide rATG/Fludarabine/HSCT
n=22 participants at risk
Conditioning regimen will be 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes/stem cells
Fludarabine: Purine analog which inhibits DNA synthesis/repair
|
|---|---|---|
|
General disorders
Scleroderma Disease Related
|
9.1%
2/22 • Number of events 2 • during treatment at 6 months then yearly for up to 5 years post transplant
|
13.6%
3/22 • Number of events 3 • during treatment at 6 months then yearly for up to 5 years post transplant
|
Other adverse events
| Measure |
Cyclophosphamide rATG/HSCT
n=22 participants at risk
Control arm will have the same conditioning regimen used in ASSIST study. The conditioning regimen will be 200 mg/kg of intravenous cyclophosphamide given in 4 equal fractions on days -5 through -2 with intravenous mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 and then 1.5 mg/kg from day-4 thru day -1. Methylprednisolone 1000 mg will be used infused intravenously before each dose of rATG. Peripheral blood stem cells (PBSC) will be infused intravenously on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and continued until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: An alkylating agent which causes prevention of cell division by forming adducts with DNA
Mesna: Medication used to decrease the risk of hemorrhagic cystitis prophylaxis
rATG: A predominantly lymphocyte-specific immunosuppressive agent which contains antibodies specific to the antigens commonl
|
Cyclophosphamide rATG/Fludarabine/HSCT
n=22 participants at risk
Conditioning regimen will be 120 mg/kg of IV cyclophosphamide given in 2 equal fractions on days -3 and -2 with IV mesna. Rabbit antithymocyte globulin (rATG) (Thymoglobulin®) will be dosed at 0.5 mg/kg on day-5 then 1.5 mg/kg from day-4 thru day -1. Fludarabine 30 mg/m2 will be given IV on days -5, -4, and -3. Methylprednisolone 1000 mg will be used infused IV before each dose of rATG. PBSC will be infused IV on day 0. Filgrastim 5-10 mcg/kg will be started on day + 5 and cont. until neutrophil engraftment.
Peripheral Blood Stem Cells: Mobilized leukapheresis product
Cyclophosphamide: Alkylating agent
Mesna: Used to decrease the risk of hemorrhagic cystitis
rATG: Immunosuppressive agent which contains antibodies specific to the antigens
Methylprednisolone: Steroid
Filgrastim: Granulocyte-colony stimulating factor (G-CSF);glycoprotein that stimulates the bone marrow to produce granulocytes/stem cells
Fludarabine: Purine analog which inhibits DNA synthesis/repair
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Plueral Effusion
|
4.5%
1/22 • Number of events 1 • during treatment at 6 months then yearly for up to 5 years post transplant
|
0.00%
0/22 • during treatment at 6 months then yearly for up to 5 years post transplant
|
|
Cardiac disorders
Disease Related Pericardial Effusion
|
9.1%
2/22 • Number of events 2 • during treatment at 6 months then yearly for up to 5 years post transplant
|
9.1%
2/22 • Number of events 2 • during treatment at 6 months then yearly for up to 5 years post transplant
|
|
Cardiac disorders
Cardiac Tamponade
|
0.00%
0/22 • during treatment at 6 months then yearly for up to 5 years post transplant
|
4.5%
1/22 • Number of events 1 • during treatment at 6 months then yearly for up to 5 years post transplant
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place