ABT-751 With Chemotherapy for Relapsed Pediatric ALL

Phase 1

Terminated

• Conditions: Recurrent Pediatric ALL; Acute Lymphoblastic Leukemia; Refractory Pediatric ALL; Relapsed Pediatric ALL
• Interventions: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine

• Registration Number: NCT00439296
• Lead Sponsor: Therapeutic Advances in Childhood Leukemia Consortium

Brief Summary

This is a phase I/II study of an investigational drug called ABT-751, produced by Abbott Laboratories, given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). The phase I portion of this study is being done to find the highest dose of ABT-751 that can be given safely in combination with other chemotherapy drugs. A safe dose is one that does not result in unacceptable side effects. After a safe dose for ABT-751 given with chemotherapy has been found, the study will add additional patients to find out if ABT-751 (given at the maximal safe dose) when given with additional chemotherapy is an effective therapy for the treatment of children with relapsed ALL. It is expected that approximately 15-35 children and young adults will take part in this study.

Detailed Description

All patients will receive the 2 courses of chemotherapy unless medical complications prevent the administration of some of the drugs. Treatment for the first 2 courses of therapy will last about 2 months.

Treatment on this study will consist of a combination of 8 anti-cancer medications. The 8 anticancer medicines are ABT-751, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), methotrexate (MTX), cyclophosphamide, and 6-thioguanine. All the drugs except ABT-751 are well known anti-cancer drugs and have been used extensively in the treatment of cancer.

During the Phase I portion of this study, when you enroll, you will be given an assigned dose of ABT-751. The dose of ABT-751 will be based on doses given in previous studies done with adults and children. At each dose level of ABT-751, between 3 and 6 children will receive ABT-751 in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of ABT-751 will not be increased. If you have bad side effects, your dose may be decreased.

The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.

Study Timeline

• Study Start: 2006-05-22
• Study First Submitted: 2007-02-21
• Study First Submitted QC: 2007-02-21
• Study First Posted: 2007-02-23
• Primary Completion: 2009-05-19
• Study Completion: 2009-09-23
• Results First Submitted: 2018-10-02
• Results First Submitted QC: 2020-08-21
• Results First Posted: 2020-09-09
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-22
• Last Update Posted: 2021-03-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Level 1	Dexamethasone	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	Doxorubicin	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	PEG-asparaginase	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	Cytarabine	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	Methotrexate	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	Cyclophosphamide	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	6-thioguanine	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	Dexamethasone	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	PEG-asparaginase	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	Doxorubicin	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	Methotrexate	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	Cytarabine	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	6-thioguanine	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	Cyclophosphamide	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	Dexamethasone	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	PEG-asparaginase	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	Doxorubicin	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	Cytarabine	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	Cyclophosphamide	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	Methotrexate	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	Doxorubicin	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	6-thioguanine	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	Dexamethasone	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	PEG-asparaginase	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	Cytarabine	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	Methotrexate	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	Dexamethasone	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	Cyclophosphamide	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	PEG-asparaginase	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	6-thioguanine	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	Cytarabine	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	Cyclophosphamide	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	Methotrexate	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	Doxorubicin	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	6-thioguanine	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	Dexamethasone	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	PEG-asparaginase	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	Cytarabine	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	Doxorubicin	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	Methotrexate	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	Cyclophosphamide	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	6-thioguanine	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	PEG-asparaginase	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	Doxorubicin	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	Dexamethasone	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	Cytarabine	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	Methotrexate	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	Cyclophosphamide	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	6-thioguanine	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 1	ABT-751	Treatment Dose of ABT-751 is 80 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 2	ABT-751	Treatment Dose of ABT-751 is 100 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 3	ABT-751	Treatment Dose of ABT-751 is 125 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 4	ABT-751	Treatment Dose of ABT-751 is 150 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 5	ABT-751	Treatment Dose of ABT-751 is 175 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level 0	ABT-751	Treatment Dose of ABT-751 is 65 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate
Dose Level -1	ABT-751	Treatment Dose of ABT-751 is 50 mg/m2/day Tx Course 1: • ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine, IT Methotrexate Tx Course 2: • Cyclophosphamide, 6-Thioguanine, IT Methotrexate, Cytarabine, PEG-asparaginase, ABT-751 Tx Courses 3-12 (maintenance courses): • ABT-751, IT Methotrexate

Primary Outcome Measures

Name	Time	Method
Number of Patients That Achieved Complete Response to ABT-751	Day 29 of Course 1	Complete response (CR) is the occurrence of all of the following on approximately Day 29: less than 5% leukemic blasts in the bone marrow aspirate with no evidence of leukemic blasts in the CSF or peripheral blood and recovery of peripheral blood counts of an Absolute neutrophil count (ANC) \> 750/μL and Platelet count \> 75,000 μL.
Number of Patients That Experienced Dose Limiting Toxicity From ABT-751	Each dose level is evaluated	ABT-751 was given daily for 21 days for a period of 28 day course in combination with dexamethasone, PEG-asparaginase, and doxorubicin. The occurrence of a dose limiting toxicity (DLT) was evaluated at the end of the 28 day course.; DLT will be defined as any of the following events that are deemed by the investigator as probably or definitely attributable to ABT-751. Toxicity grade follows the CTCAE criteria, version 3.0. A copy of the CTCAE can be downloaded from the CTEP home page (http://ctep.cancer.gov).; * Grade 3 or 4 Ileus; * Grade 3 or 4 Constipation; * Grade 3 or 4 Gastrointestinal obstruction, any location; * Grade 3 or 4 Sensory Neuropathy; * Grade 3 or 4 Motor Neuropathy; * Grade 3 or 4 Neuropathic pain lasting longer than 24 hours despite medical intervention; * Grade 3 or 4 Hypoxia in the absence of anemia or infection; * Grade 4 Alanine aminotransferase (ALT) which does not return to

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Occurrence of Toxic Death	From the first dose of study therapy until 30 days after last therapy dose. Last dose protocol therapy is on day 21.	The occurrence of toxic death at anytime that is definitely, probably or possibly related to the treatment.

Trial Locations

Locations (5)

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

Childrens Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

C.S. Mott Children's Hospital; 🇺🇸 Ann Arbor, Michigan, United States

UCSF School of Medicine; 🇺🇸 San Francisco, California, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States