Trial Outcomes & Findings for A Trial of Temsirolimus With Etoposide and Cyclophosphamide in Children With Relapsed Acute Lymphoblastic Leukemia and Non-Hodgkins Lymphoma (NCT NCT01614197)

Last Updated: 2023-07-27

Results Overview

The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy. All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

16 participants

Primary outcome timeframe

Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)

Results posted on

2023-07-27

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Overall Study STARTED	3	4	6	3
Overall Study COMPLETED	3	3	6	3
Overall Study NOT COMPLETED	0	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Dose Level 1 This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Overall Study Withdrawal by Subject	0	1	0	0

Baseline Characteristics

Total number of patients that were enrolled onto the study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 n=3 Participants This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 n=4 Participants If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 n=6 Participants If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 n=3 Participants If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=93 Participants	4 Participants n=4 Participants	6 Participants n=27 Participants	3 Participants n=483 Participants	16 Participants n=36 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Sex: Female, Male Female	0 Participants n=93 Participants	0 Participants n=4 Participants	4 Participants n=27 Participants	2 Participants n=483 Participants	6 Participants n=36 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	4 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	10 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	1 Participants n=4 Participants	6 Participants n=27 Participants	1 Participants n=483 Participants	8 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=93 Participants	3 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants	7 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 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	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Race (NIH/OMB) White	3 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants	1 Participants n=483 Participants	10 Participants n=36 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	3 Participants n=27 Participants	1 Participants n=483 Participants	4 Participants n=36 Participants
Region of Enrollment Canada	1 participants n=93 Participants	1 participants n=4 Participants	0 participants n=27 Participants	0 participants n=483 Participants	2 participants n=36 Participants
Region of Enrollment United States	2 participants n=93 Participants	3 participants n=4 Participants	6 participants n=27 Participants	2 participants n=483 Participants	13 participants n=36 Participants
Region of Enrollment Australia	0 participants n=93 Participants	0 participants n=4 Participants	0 participants n=27 Participants	1 participants n=483 Participants	1 participants n=36 Participants
Prior Therapy Regimens # of prior therapies : 1 prior therapy	0 Participants n=93 Participants • Total number of patients that were enrolled onto the study	0 Participants n=4 Participants • Total number of patients that were enrolled onto the study	0 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	0 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 2 prior therapies	0 Participants n=93 Participants • Total number of patients that were enrolled onto the study	1 Participants n=4 Participants • Total number of patients that were enrolled onto the study	1 Participants n=27 Participants • Total number of patients that were enrolled onto the study	1 Participants n=483 Participants • Total number of patients that were enrolled onto the study	3 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 3 prior therapies	2 Participants n=93 Participants • Total number of patients that were enrolled onto the study	1 Participants n=4 Participants • Total number of patients that were enrolled onto the study	2 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	5 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 4 prior therapies	0 Participants n=93 Participants • Total number of patients that were enrolled onto the study	0 Participants n=4 Participants • Total number of patients that were enrolled onto the study	0 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	0 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 5 prior therapies	0 Participants n=93 Participants • Total number of patients that were enrolled onto the study	1 Participants n=4 Participants • Total number of patients that were enrolled onto the study	1 Participants n=27 Participants • Total number of patients that were enrolled onto the study	2 Participants n=483 Participants • Total number of patients that were enrolled onto the study	4 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 6 prior therapies	0 Participants n=93 Participants • Total number of patients that were enrolled onto the study	0 Participants n=4 Participants • Total number of patients that were enrolled onto the study	0 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	0 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens # of prior therapies : 7 prior therapies	1 Participants n=93 Participants • Total number of patients that were enrolled onto the study	0 Participants n=4 Participants • Total number of patients that were enrolled onto the study	2 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	3 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens Prior transplant : Yes	2 Participants n=93 Participants • Total number of patients that were enrolled onto the study	2 Participants n=4 Participants • Total number of patients that were enrolled onto the study	4 Participants n=27 Participants • Total number of patients that were enrolled onto the study	0 Participants n=483 Participants • Total number of patients that were enrolled onto the study	8 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens Prior transplant : No	1 Participants n=93 Participants • Total number of patients that were enrolled onto the study	1 Participants n=4 Participants • Total number of patients that were enrolled onto the study	2 Participants n=27 Participants • Total number of patients that were enrolled onto the study	3 Participants n=483 Participants • Total number of patients that were enrolled onto the study	7 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens Prior CAR-T cell therapy : Yes	1 Participants n=93 Participants • Total number of patients that were enrolled onto the study	0 Participants n=4 Participants • Total number of patients that were enrolled onto the study	2 Participants n=27 Participants • Total number of patients that were enrolled onto the study	1 Participants n=483 Participants • Total number of patients that were enrolled onto the study	4 Participants n=36 Participants • Total number of patients that were enrolled onto the study
Prior Therapy Regimens Prior CAR-T cell therapy : No	2 Participants n=93 Participants • Total number of patients that were enrolled onto the study	3 Participants n=4 Participants • Total number of patients that were enrolled onto the study	4 Participants n=27 Participants • Total number of patients that were enrolled onto the study	2 Participants n=483 Participants • Total number of patients that were enrolled onto the study	11 Participants n=36 Participants • Total number of patients that were enrolled onto the study

PRIMARY outcome

Timeframe: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)

Population: Number of patients that initiated and completed study treatment.

Outcome measures

Outcome measures
Measure	Dose Level 1 n=3 Participants This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 n=3 Participants If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 n=6 Participants If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 n=3 Participants If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Number of Patients That Experienced DLT During Cycle 1 of Therapy Number of patients that did not experience DLT	3 Participants	3 Participants	5 Participants	3 Participants
Number of Patients That Experienced DLT During Cycle 1 of Therapy Number of patient that did experience DLT	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)

Population: All these analyses will be descriptive and exploratory and hypotheses generating in nature.

CR = Complete remission defined as attainment of bone marrow with \<5% blasts with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil counts (ANC) \> or = to 500/uL and platelet count \> or = to 50,000 microliters) CRi = Complete remission with incomplete blood count recovery defined as attainment of bone marrow with \>5% blasts with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC \< 500/uL or platelets \< 50,000 microliters PR = partial remission defined as complete disappearance of circulating blasts and achievement of 5-25% blasts if greater than 25% blasts originally without new sites of extramedullary disease and with recovery of ANC. SD = stable disease defined as not satisfying criteria for PD, or has recovery of ANC \> or = to 500/uL and fails to qualify for CR, CRi, or PR PD = progressive disease defined as an increase of at least 25% in bone marrow leukemic cells

Outcome measures

Outcome measures
Measure	Dose Level 1 n=3 Participants This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 n=3 Participants If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 n=6 Participants If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 n=3 Participants If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Response Rate at the Completion of 1 Cycle of Study Treatment CR	0 Participants	1 Participants	1 Participants	0 Participants
Response Rate at the Completion of 1 Cycle of Study Treatment CRi	1 Participants	0 Participants	0 Participants	1 Participants
Response Rate at the Completion of 1 Cycle of Study Treatment PR	1 Participants	1 Participants	1 Participants	0 Participants
Response Rate at the Completion of 1 Cycle of Study Treatment SD	0 Participants	1 Participants	1 Participants	1 Participants
Response Rate at the Completion of 1 Cycle of Study Treatment PD	1 Participants	0 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Cycle 1 (a minimum of 4 weeks and a max of 8 weeks)

MRD positive is defined as \> or = to 0.1% MRD MRD negative is define as \< 0.1% MRD All these analyses will be descriptive and exploratory and hypotheses generating in nature.

Outcome measures

Outcome measures
Measure	Dose Level 1 n=3 Participants This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 n=3 Participants If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 n=6 Participants If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 n=3 Participants If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients MRD positive	3 Participants	2 Participants	5 Participants	2 Participants
Minimum Residual Disease (MRD) Levels Present at End of Cycle 1 Therapy in Patients MRD negative	0 Participants	1 Participants	1 Participants	1 Participants

Adverse Events

Dose Level 1

Serious events: 3 serious events

Other events: 3 other events

Deaths: 3 deaths

Dose Level 2

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Dose Level 3

Serious events: 3 serious events

Other events: 6 other events

Deaths: 3 deaths

Dose Level 4

Serious events: 0 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 n=3 participants at risk This is the starting dose of temsirolimus at 7.5 mg/m\^2 given IV. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 2 n=3 participants at risk If Dose Level 1 is tolerated, the study will escalate to Dose Level 2 following the dose escalation schedule. Dose Level 2 will be administered via IV at 10 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 3 n=6 participants at risk If Dose Level 2 is tolerated, the study will escalate to Dose Level 3 following the dose escalation schedule. Dose Level 3 will be administered via IV at 15 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.	Dose Level 4 n=3 participants at risk If Dose Level 3 is tolerated, the study will escalate to Dose Level 4 following the dose escalation schedule. Dose Level 4 will be administered via IV at 25 mg/m\^2. First dose of temsirolimus will be administered on Day 1, followed immediately by the first dose of IV etoposide and IV cyclophosphamide. Etoposide and cyclophosphamide are continued for the next four days (Day 1-5). A second dose of temsirolimus is given on Day 8. Temsirolimus will not be escalated beyond Dose Level 4. Temsirolimus: Dose will be assigned at study entry. Give IV over 30 minutes on days 1 and 8. Etoposide: 100 mg/m2 IV over 1-2 hours daily x 5 on Days 1-5. Cyclophosphamide: 440 mg/m2 IV daily x 5 on Days 1-5 given over 30-60 minutes.
Gastrointestinal disorders Abdominal Pain	33.3% 1/3 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/6 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Gastrointestinal disorders Ascites	33.3% 1/3 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/6 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Cardiac disorders Cardiac arrest	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Blood and lymphatic system disorders Febrile neutropenia	66.7% 2/3 • Number of events 2 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/6 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
General disorders Fever	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Vascular disorders Hematoma	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 1/3 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/6 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Infections and infestations Lung infection	33.3% 1/3 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Cardiac disorders Pericardial effusion	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Pulmonary edema	33.3% 1/3 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/6 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	16.7% 1/6 • Number of events 1 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.	0.00% 0/3 • Up to 60 days The definition of adverse event and/or serious adverse event used to collect adverse event information is the same as clinicaltrials.gov.

Other adverse events

Additional Information

Roy Leong

Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL)

Phone: 323-361-5132

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place