Trial Outcomes & Findings for Trial of Sirolimus and Methotrexate in Relapsed/Refractory Lymphoblastic Leukemia and Lymphoma (NCT NCT01162551)
NCT ID: NCT01162551
Last Updated: 2019-08-06
Results Overview
Number of participants who achieve a Complete Response (CR), Complete Response with in the absence of total platelet recovery (CRp), or Partial Response (PR). Per response criteria in this protocol: Complete Response (CR) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease and recovery of peripheral blood counts (absolute neutrophil count (ANC)\> 500/μL and platelets \> 50,000/ μL); Complete Response in the absence of total platelet recovery (CRp) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease with recovery of peripheral blood counts except for platelets (ANC\> 500/μL, platelets \< 50,000uL); and Partial Response (PR) - M2 bone marrow (5% but \<25% blasts), with no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts (ANC \> 500/μL and platelets \>50,000/μL).
COMPLETED
PHASE2
5 participants
Day 28
2019-08-06
Participant Flow
Participant milestones
| Measure |
Sirolimus and Methotrexate
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Overall Study
STARTED
|
3
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Sirolimus and Methotrexate
n=5 Participants
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
12 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
5 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 28Number of participants who achieve a Complete Response (CR), Complete Response with in the absence of total platelet recovery (CRp), or Partial Response (PR). Per response criteria in this protocol: Complete Response (CR) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease and recovery of peripheral blood counts (absolute neutrophil count (ANC)\> 500/μL and platelets \> 50,000/ μL); Complete Response in the absence of total platelet recovery (CRp) - M1 bone marrow (\<5% blasts) with no evidence of circulating blasts or extramedullary disease with recovery of peripheral blood counts except for platelets (ANC\> 500/μL, platelets \< 50,000uL); and Partial Response (PR) - M2 bone marrow (5% but \<25% blasts), with no evidence of circulating blasts or extramedullary disease and normalization of peripheral blood counts (ANC \> 500/μL and platelets \>50,000/μL).
Outcome measures
| Measure |
Sirolimus and Methotrexate
n=3 Participants
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Response Rate
CR
|
0 participants
|
|
Response Rate
CRp
|
0 participants
|
|
Response Rate
PR
|
0 participants
|
SECONDARY outcome
Timeframe: Day 28Population: 3 patients had weekly sirolimus levels analyzed.
One goal of this study is to maintain trough levels of sirolimus within a certain range. The outcome measure counts the number of dose adjustments up or down that were needed to meet goal level based on weekly tough level measurements.
Outcome measures
| Measure |
Sirolimus and Methotrexate
n=9 blood samples
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Number of Dose Adjustments To Maintain Trough Levels
Dose level increase
|
2 Dose level adjustments
|
|
Number of Dose Adjustments To Maintain Trough Levels
Dose level decrease
|
1 Dose level adjustments
|
Adverse Events
Sirolimus and Methotrexate
Serious adverse events
| Measure |
Sirolimus and Methotrexate
n=3 participants at risk
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
33.3%
1/3 • Number of events 1 • 4.5 years
|
|
Renal and urinary disorders
Hematuria
|
33.3%
1/3 • Number of events 1 • 4.5 years
|
|
Cardiac disorders
torsades
|
33.3%
1/3 • Number of events 1 • 4.5 years
|
Other adverse events
| Measure |
Sirolimus and Methotrexate
n=3 participants at risk
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days
Sirolimus and Methotrexate: Single Arm Efficacy Trial:
Sirolimus: Oral bolus on day 1, then daily oral dose days 2-28. Dose will be altered to maintain a sirolimus trough level between ≥ 8 and ≤ 13. Trough levels will be checked weekly.
Methotrexate: Oral 20 mg/m2/week on Days 2, 9, 16, 23.
One cycle is 28 days.
|
|---|---|
|
Blood and lymphatic system disorders
Cytopenias
|
66.7%
2/3 • Number of events 2 • 4.5 years
|
|
Metabolism and nutrition disorders
electrolyte abnormalitles
|
66.7%
2/3 • Number of events 2 • 4.5 years
|
|
General disorders
fever
|
33.3%
1/3 • Number of events 1 • 4.5 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place