Trial Outcomes & Findings for Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia (NCT NCT00186875)

Last Updated: 2017-07-28

Results Overview

The "response rate" is defined as the proportion of participants who attain morphological complete remission after the re-induction Block C, inclusive of all patients who begin re-induction. Morphological complete remission was defined as \<5% blasts in bone marrow by morphology.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

47 participants

Primary outcome timeframe

End of re-induction Block C (approximately 1 month after the start of therapy)

Results posted on

2017-07-28

Participant Flow

Between May 2004 and August 2012, this study enrolled 47 participants with relapsed or refractory acute lymphoblastic leukemia (ALL): 40 were enrolled at St. Jude and 7 at Rady Children's Hospital.

Seven participants were excluded from analysis: 6 who enrolled and received treatment prior to a therapy change in amendment 1.0 and one who was incorrectly enrolled on this study. Forty participants were included in the analysis.

Participant milestones

Participant milestones
Measure	Standard Risk Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.
Overall Study STARTED	26	14
Overall Study COMPLETED	26	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapy for Pediatric Relapsed or Refractory Acute Lymphoblastic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Total n=40 Participants Total of all reporting groups	Standard Risk n=26 Participants Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=14 Participants Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.
Age, Continuous	10 Years n=5 Participants	9.7 Years n=5 Participants	12 Years n=7 Participants
Sex: Female, Male Female	14 Participants n=5 Participants	9 Participants n=5 Participants	5 Participants n=7 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	17 Participants n=5 Participants	9 Participants n=7 Participants

PRIMARY outcome

Timeframe: End of re-induction Block C (approximately 1 month after the start of therapy)

Population: Response is defined as morphological complete remission after re-induction Block C. Participants who begin re-induction phase but fail to reach the end of Block C for whatever reason will be regarded as an induction failure.

Outcome measures

Outcome measures
Measure	Standard Risk n=26 Participants Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=14 Participants Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.	TOTXV Participants Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. Participants received high-dose methotrexate infusion in upfront window treatment as described in NCT00137111.
Response Rate Complete remission	0.846 proportion of participants	0.786 proportion of participants	—
Response Rate Failure to reach complete remission	0.154 proportion of participants	0.214 proportion of participants	—

PRIMARY outcome

Timeframe: 2 years after last patient completes therapy (approximately 4 years after enrollment)

OS is measured from the start of on-study to the date of death or to the last date of follow-up. Measurement is determined by Kaplan-Meyer estimate. The probability of survival at 5 years after diagnosis is given.

Outcome measures

Outcome measures
Measure	Standard Risk n=26 Participants Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=14 Participants Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.	TOTXV Participants Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. Participants received high-dose methotrexate infusion in upfront window treatment as described in NCT00137111.
Overall Survival (OS)	0.654 probability Standard Deviation 0.103	0.357 probability Standard Deviation 0.120	—

OTHER_PRE_SPECIFIED outcome

Timeframe: End of Block Block C therapy (Day 46)

Population: Protocol information for the comparison group of TOTXV Participants, including Participant Flow, Baseline Characteristics, and Adverse Events, is available on ClinicalTrials.gov under registration ID NCT00137111.

The prevalence of MRD in children undergoing treatment for relapsed ALL and to compare the results to those obtained in children with newly diagnosed ALL. MRD is considered as positive (i.e., prevalent) if its level is \>=0.01%. The prevalence of MRD after Block C is defined as the proportion of MRD positives.

Outcome measures

Outcome measures
Measure	Standard Risk n=20 Participants Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=9 Participants Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.	TOTXV Participants n=492 Participants Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. Participants received high-dose methotrexate infusion in upfront window treatment as described in NCT00137111.
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111) Negative <0.01%	11 Participants	1 Participants	390 Participants
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111) Positive ≥0.01%	9 Participants	8 Participants	102 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: End of Block B therapy (Day 19)

Outcome measures

Outcome measures
Measure	Standard Risk n=22 Participants Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=12 Participants Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.	TOTXV Participants n=488 Participants Total therapy applies to all eligible patients and includes remission induction, consolidation, and continuation therapy. Participants received high-dose methotrexate infusion in upfront window treatment as described in NCT00137111.
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111) Negative <0.01%	11 Participants	2 Participants	191 Participants
Minimal Residual Disease (MRD) Compared With Historical Data From TOTXV Protocol (NCT00137111) Positive ≥0.01%	11 Participants	10 Participants	297 Participants

Adverse Events

Standard Risk

Serious events: 6 serious events

Other events: 26 other events

Deaths: 0 deaths

High Risk

Serious events: 2 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Standard Risk n=26 participants at risk Participants with isolated extramedullary relapse (with blasts in bone marrow (BM) \<5%) regardless of the timing of relapse, and participants with B-lineage ALL who develop a late hematological relapse (isolated BM or combined).	High Risk n=14 participants at risk Participants with T-cell ALL who develop a hematological \[isolated bone marrow (BM) or combined\] relapse, irrespective of length of initial remission, participants with B-lineage ALL who develop early hematological relapse (isolated BM or combined), and participants relapsing after hematopoietic stem cell transplantation.
Immune system disorders Allergic reaction/hypersensitivity (including drug fever)	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Blood and lymphatic system disorders Iron overload	0.00% 0/26 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Cardiac disorders Prolonged QTc interval	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Cardiac disorders Supraventricular and nodal arrhythmia, supraventricular tachycardia	0.00% 0/26 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 3 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Cardiac disorders Ventricular arrhythmia, ventricular arrhythmia NOS	0.00% 0/26 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Cardiac disorders Hypotension	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 2 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Gastrointestinal disorders Typhlitis (cecal inflammation)	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Gastrointestinal disorders Ulcer, GI, Stomach	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Blood and lymphatic system disorders Hemorrhage, GI, Stomach	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Infections and infestations Infection, blood	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Infections and infestations Infection, brain (encephalitis, infectious)	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Infections and infestations Infection, Catheter-related	3.8% 1/26 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	0.00% 0/14 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/26 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.
Renal and urinary disorders Renal failure	0.00% 0/26 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.	7.1% 1/14 • Number of events 1 • Adverse events were collected from the time a participant began therapy through 30 days after completion of protocol therapy. The Other Adverse Events section includes reports of events, Grades 1 through 5.

Other adverse events

Additional Information

Sima Jeha, MD

St. Jude Children's Research Hospital

Phone: 866-278-5833

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place