Trial Outcomes & Findings for Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis (NCT NCT01104025)
NCT ID: NCT01104025
Last Updated: 2020-10-19
Results Overview
To determine the overall survival of patients with hemophagocytic lymphohistiocytosis at 8 weeks after an ATG/etoposide-based induction regimen and to determine the feasibility of this approach in the context of a multicenter clinical trial.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
31 participants
Primary outcome timeframe
8 Weeks
Results posted on
2020-10-19
Participant Flow
Participant milestones
| Measure |
Induction Therapy
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients.
|
|---|---|
|
Treatment Period
STARTED
|
31
|
|
Treatment Period
COMPLETED
|
25
|
|
Treatment Period
NOT COMPLETED
|
6
|
|
Follow up Until BMT OR 6 Months
STARTED
|
25
|
|
Follow up Until BMT OR 6 Months
COMPLETED
|
22
|
|
Follow up Until BMT OR 6 Months
NOT COMPLETED
|
3
|
|
Follow up Until Day 100 Post BMT
STARTED
|
11
|
|
Follow up Until Day 100 Post BMT
COMPLETED
|
9
|
|
Follow up Until Day 100 Post BMT
NOT COMPLETED
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Hybrid Immunotherapy for Hemophagocytic LymphoHistiocytosis
Baseline characteristics by cohort
| Measure |
Induction Therapy
n=31 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Age, Categorical
<=18 years
|
31 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 8 WeeksTo determine the overall survival of patients with hemophagocytic lymphohistiocytosis at 8 weeks after an ATG/etoposide-based induction regimen and to determine the feasibility of this approach in the context of a multicenter clinical trial.
Outcome measures
| Measure |
Induction Therapy
n=31 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Overall Survival
|
25 Participants
|
SECONDARY outcome
Timeframe: 8 WeeksPopulation: Patients assessed for disease features and classified each week per definition of complete response in order to determine the time at which they achieved complete response.
To determine the median time to complete response during 8 weeks of therapy
Outcome measures
| Measure |
Induction Therapy
n=11 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Time to Response
|
4 weeks
Interval 2.0 to 7.0
|
SECONDARY outcome
Timeframe: up to day 180To determine overall survival prior to the initiation of BMT (bone marrow transplant) preparative regimen (or day 180, if BMT preparative regimen not yet begun)
Outcome measures
| Measure |
Induction Therapy
n=31 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Overall Survival
|
22 Participants
|
SECONDARY outcome
Timeframe: up to 180 daysPopulation: all patients surviving to BMT or day 180 and achieving complete or partial response
To determine the frequency of disease reactivation prior to initiation of BMT preparative regimen (or day 180, if BMT preparative regimen not yet begun)
Outcome measures
| Measure |
Induction Therapy
n=21 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Number of Participants Who Experienced Reactivation
|
4 Participants
|
SECONDARY outcome
Timeframe: up to day 280To determine overall survival to day +100 after BMT, for patients who have undergone BMT within 6 months of study entry
Outcome measures
| Measure |
Induction Therapy
n=11 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Overall Survival to Day +100
|
9 Participants
|
SECONDARY outcome
Timeframe: up to day 180To determine the rate of complete response at the time of BMT preparative regimen initiation
Outcome measures
| Measure |
Induction Therapy
n=11 Participants
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Disease Status at BMT
|
8 Participants
|
Adverse Events
Induction Therapy
Serious events: 22 serious events
Other events: 31 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Induction Therapy
n=31 participants at risk
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Blood and lymphatic system disorders
hospitalization
|
22.6%
7/31 • Number of events 8 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Respiratory, thoracic and mediastinal disorders
respiratory failure
|
12.9%
4/31 • Number of events 4 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Renal and urinary disorders
acute kidney injury
|
9.7%
3/31 • Number of events 3 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Nervous system disorders
status epilepticus
|
3.2%
1/31 • Number of events 1 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Vascular disorders
multiple organ failure
|
12.9%
4/31 • Number of events 4 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Eye disorders
herpetic keratitis
|
3.2%
1/31 • Number of events 1 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Vascular disorders
hypotension
|
9.7%
3/31 • Number of events 3 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
Other adverse events
| Measure |
Induction Therapy
n=31 participants at risk
ATG, rabbit: intravenous, 5 mg/kg/dose, 5 consecutive days Dexamethasone: intravenous, 20mg/m2/day x7days, 10mg/m2/day x7days, 5mg/m2/day x14days, 2.5mg/m2/day x14days, 1.25mg/m2/day x14days Etoposide: intravenous, 150 mg/m2 weekly, starting 7 days after first dose of Thymoglobulin Methotrexate and hydrocortisone: intrathecal to patients with central nervous system involvement, age\< 1 yr: 6/8mg (MTX/HC), 1-2 yrs: 8/10mg, 2-3 yrs: 10/12mg, \>3 yrs: 12/15 mg, on day 7, 14, 21 and 42
ATG, rabbit: ATG, rabbit (Thymoglobulin, Genzyme) will be dosed at 5 mg/kg/dose, given IV on 5 consecutive days (titrated over 4 to 8 hours).
Etoposide: Etoposide will be dosed at 150mg/m2, given IV. The first dose will be given 7 days (+/- 2 days) after the first dose of ATG, and be given weekly for a total of 7 doses.
Methotrexate: Intrathecal Methotrexate and hydrocortisone will be administered to CNS+ patients
|
|---|---|
|
Immune system disorders
fever
|
96.8%
30/31 • Number of events 40 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Blood and lymphatic system disorders
anemia
|
100.0%
31/31 • Number of events 31 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Blood and lymphatic system disorders
hemorrhage
|
16.1%
5/31 • Number of events 5 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Vascular disorders
hypertension
|
9.7%
3/31 • Number of events 3 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
|
Blood and lymphatic system disorders
thrombosis
|
6.5%
2/31 • Number of events 2 • Adverse event data were collected over the 8 weeks of the treatment period. All cause mortality was assessed up to day +100 after BMT, if participant proceeded to BMT by day 180. If participant did not proceed to BMT by day 180, all cause mortality was only assessed until day 180.
|
Additional Information
Michael Jordan, MD
Cincinnati Children's Hospital Medical Center
Phone: 513-803-9063
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place