Trial Outcomes & Findings for Low Dose IL-2, Hematopoietic Stem Cell Transplantation, IL2 for GVHD (NCT NCT00539695)
NCT ID: NCT00539695
Last Updated: 2018-05-04
Results Overview
Assessment of the safety and the toxicity of low-dose IL-2, administered according to the dosage described in this protocol, in this group of patients The outcome measure is the proportion of participants with dose limiting toxicities.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
6-12 weeks
Results posted on
2018-05-04
Participant Flow
Participant milestones
| Measure |
IL2 Administration
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
Evaluable Patients
|
22
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Low Dose IL-2, Hematopoietic Stem Cell Transplantation, IL2 for GVHD
Baseline characteristics by cohort
| Measure |
IL2 Administration
n=22 Participants
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
|
|---|---|
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Age, Continuous
less than 20 yrs
|
13 years
n=93 Participants
|
|
Age, Continuous
greater and equal 20 yrs
|
47.5 years
n=93 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
|
Region of Enrollment
United States
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22 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 6-12 weeksAssessment of the safety and the toxicity of low-dose IL-2, administered according to the dosage described in this protocol, in this group of patients The outcome measure is the proportion of participants with dose limiting toxicities.
Outcome measures
| Measure |
IL2 Administration
n=22 Participants
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
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|---|---|
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Rate of Dose Limiting Toxicities
|
0.045 proportion of participants of DLT
Interval 0.001 to 0.228
|
SECONDARY outcome
Timeframe: Up to 12 weeks on low-dose IL-2Population: Participants received low-dose IL-2
To determine the efficacy of low-dose IL-2 in the prevention of severe (grade III or IV) acute GVHD
Outcome measures
| Measure |
IL2 Administration
n=22 Participants
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
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|---|---|
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Rate of Severe (Grade III or IV) Acute GVHD
|
4.5 percentage of participants
Interval 0.12 to 22.8
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SECONDARY outcome
Timeframe: 12 weeksPopulation: Participants received low-dose IL-2 and had pre and post IL-2 Treg measurements.
To investigate the immunomodulatory effects of IL-2 administered after allogeneic hematopoietic stem cell transplantation
Outcome measures
| Measure |
IL2 Administration
n=16 Participants
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
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|---|---|
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Percentage Change in CD4+ CD25+ FoxP3+ Regulatory T Cells (Tregs) From Pre to Post IL-2 Infusions
|
55.6 percentage
Interval -37.8 to 417.7
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OTHER_PRE_SPECIFIED outcome
Timeframe: 12 weeksTo conduct ancillary studies on those patients to investigate before, during and after IL-2 administration to determine: * The immunophenotype of PBMCs * The suppressive activity of CD4+ CD25+ FoxP3+ Tregs * Cytokines secreted by PBMCs * NK cell analysis
Outcome measures
Outcome data not reported
Adverse Events
IL2 Administration
Serious events: 10 serious events
Other events: 22 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
IL2 Administration
n=22 participants at risk
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
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|---|---|
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Gastrointestinal disorders
Anorexia
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Colitis, infectious (e.g., Clostridium difficile)
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Dehydration
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Fatigue (lethargy, malaise, asthenia)
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe
|
4.5%
1/22 • Number of events 1
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
13.6%
3/22 • Number of events 3
|
|
Gastrointestinal disorders
Gastrointestinal - Other: Gall Bladder
|
4.5%
1/22 • Number of events 1
|
|
Blood and lymphatic system disorders
Hemorrhage, CNS
|
4.5%
1/22 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection (documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC <1.0 x 10e
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection - Other: GNR Line Infection (B Cepacia complex)
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection - Other: Gastrointestinal_Abdomen
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection - Other: Parainfluenza
|
4.5%
1/22 • Number of events 1
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
4.5%
1/22 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash: erythema multiforme (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
|
4.5%
1/22 • Number of events 1
|
|
Vascular disorders
Thrombosis/thrombus/embolism
|
4.5%
1/22 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
1/22 • Number of events 1
|
Other adverse events
| Measure |
IL2 Administration
n=22 participants at risk
SCHEDULE OF IL-2 ADMINISTRATION: Patients will receive a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT.
Time will be measured as 'week beginning with first IL-2 injection.'
T cell Induction via IL-2 to reduce GVHD
IL-2: IL2 Administration:
Patients will be given a fixed dose (1x10e5 units/m2/dose) of IL-2 given as a subcutaneous injection three times weekly (separated by at least one day) for 6 weeks beginning no earlier than day +7 after HSCT but beginning no later than 30 days after HSCT. If the patient has not developed \>grade I side effects to IL-2 and has not developed \>grade I GVHD then the patient may continue the IL-2 for 6 additional weeks. Time will be measured as 'week beginning with first IL-2 injection.
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|---|---|
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Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
40.9%
9/22 • Number of events 48
|
|
Metabolism and nutrition disorders
AST, SGOT(serum glutamic oxaloacetic transaminase)
|
59.1%
13/22 • Number of events 48
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
54.5%
12/22 • Number of events 42
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
13.6%
3/22 • Number of events 8
|
|
Gastrointestinal disorders
Anorexia
|
9.1%
2/22 • Number of events 3
|
|
Metabolism and nutrition disorders
Bicarbonate, serum-low
|
22.7%
5/22 • Number of events 16
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
13.6%
3/22 • Number of events 11
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
63.6%
14/22 • Number of events 67
|
|
Gastrointestinal disorders
Constipation
|
22.7%
5/22 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
22.7%
5/22 • Number of events 12
|
|
Metabolism and nutrition disorders
Creatinine
|
22.7%
5/22 • Number of events 9
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
11/22 • Number of events 31
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
36.4%
8/22 • Number of events 11
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
18.2%
4/22 • Number of events 4
|
|
Blood and lymphatic system disorders
Edema: head and neck
|
9.1%
2/22 • Number of events 2
|
|
Blood and lymphatic system disorders
Edema: limb
|
13.6%
3/22 • Number of events 4
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
27.3%
6/22 • Number of events 13
|
|
Gastrointestinal disorders
Fatigue (lethargy, malaise, asthenia)
|
36.4%
8/22 • Number of events 14
|
|
Infections and infestations
Febrile neutropenia (fever of unknown origin without clinically or microbiologically documented infe
|
9.1%
2/22 • Number of events 2
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)
|
40.9%
9/22 • Number of events 31
|
|
Metabolism and nutrition disorders
GGT (gamma-Glutamyl transpeptidase)
|
31.8%
7/22 • Number of events 27
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
18.2%
4/22 • Number of events 11
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
13.6%
3/22 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Hyperpigmentation
|
13.6%
3/22 • Number of events 3
|
|
Cardiac disorders
Hypertension
|
13.6%
3/22 • Number of events 4
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Catheter-related
|
9.1%
2/22 • Number of events 2
|
|
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS
|
9.1%
2/22 • Number of events 4
|
|
Skin and subcutaneous tissue disorders
Injection site reaction/extravasation changes
|
13.6%
3/22 • Number of events 3
|
|
General disorders
Insomnia
|
9.1%
2/22 • Number of events 2
|
|
Metabolism and nutrition disorders
Magnesium, serum-high (hypermagnesemia)
|
13.6%
3/22 • Number of events 5
|
|
Metabolism and nutrition disorders
Magnesium, serum-low (hypomagnesemia)
|
40.9%
9/22 • Number of events 30
|
|
Nervous system disorders
Mood alteration - Anxiety
|
9.1%
2/22 • Number of events 4
|
|
Nervous system disorders
Mood alteration - Depression
|
9.1%
2/22 • Number of events 3
|
|
Gastrointestinal disorders
Mucositis/stomatitis (clinical exam) - Oral cavity
|
9.1%
2/22 • Number of events 5
|
|
Gastrointestinal disorders
Nausea
|
81.8%
18/22 • Number of events 50
|
|
Nervous system disorders
Neuropathy: sensory
|
22.7%
5/22 • Number of events 7
|
|
General disorders
PTT (Partial Thromboplastin Time)
|
13.6%
3/22 • Number of events 4
|
|
General disorders
Pain - Abdomen NOS
|
36.4%
8/22 • Number of events 11
|
|
General disorders
Pain - Back
|
13.6%
3/22 • Number of events 3
|
|
General disorders
Pain - Bone
|
13.6%
3/22 • Number of events 4
|
|
General disorders
Pain - Head/headache
|
45.5%
10/22 • Number of events 18
|
|
General disorders
Pain - Joint
|
9.1%
2/22 • Number of events 2
|
|
General disorders
Pain - Other: Abdomen
|
9.1%
2/22 • Number of events 5
|
|
General disorders
Pain - Other: Dysuria
|
9.1%
2/22 • Number of events 2
|
|
Metabolism and nutrition disorders
Phosphate, serum-low (hypophosphatemia)
|
9.1%
2/22 • Number of events 2
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
18.2%
4/22 • Number of events 9
|
|
Skin and subcutaneous tissue disorders
Pruritus/itching
|
18.2%
4/22 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary/Upper Respiratory - Other: Rhinorrhea
|
13.6%
3/22 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
59.1%
13/22 • Number of events 27
|
|
Renal and urinary disorders
Renal/Genitourinary - Other: Dysuria
|
9.1%
2/22 • Number of events 2
|
|
General disorders
Rigors/chills
|
13.6%
3/22 • Number of events 4
|
|
Metabolism and nutrition disorders
Sodium, serum-high (hypernatremia)
|
9.1%
2/22 • Number of events 4
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
36.4%
8/22 • Number of events 24
|
|
Nervous system disorders
Tremor
|
9.1%
2/22 • Number of events 2
|
|
Metabolism and nutrition disorders
Triglyceride, serum-high (hypertriglyceridemia)
|
18.2%
4/22 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
54.5%
12/22 • Number of events 43
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place