Clinical trial NCT00439296
Conditions: Recurrent Pediatric ALL Relapsed Pediatric ALL Acute Lymphoblastic Leukemia Refractory Pediatric ALL
Keywords: Acute Lymphoblastic Leukemia Pediatrics Relapsed Recurrence ABT-751 Therapeutic Advances in Childhood Leukemia Investigational Childhood ALL Relapsed ALL Refractory ALL Relapsed pediatric ALL Refractory pediatric ALL TACL
Sponsor: Therapeutic Advances in Childhood Leukemia Consortium
Start date: 2006-05-22; Completion date: 2009-09-23
Enrollment: 9 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

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.

Arms: arm 1: 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 arm 2: 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 arm 3: 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 arm 4: 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 arm 5: 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 arm 6: 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 arm 7: 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
Interventions: intervention 1: ABT-751 intervention 2: Dexamethasone intervention 3: PEG-asparaginase intervention 4: Doxorubicin intervention 5: Cytarabine intervention 6: Methotrexate intervention 7: Cyclophosphamide intervention 8: 6-thioguanine
Intervention descriptions: intervention 1: Treatment Course 1:

Oral capsule to be given daily for 21 days at assigned dose.

Treatment Course 2:

ABT-751 will be taken once daily, by mouth, at the assigned dose on days 15-35.

Treatment Course 3:

ABT-751 will be taken once daily, by mouth, at the assigned dose on days 1-21 followed by 1 week of rest. intervention 2: In Treatment Course 1 only:

* 10 mg/m2/day divided BID.
* Take dexamethasone by mouth days 1-14. intervention 3: In Treatment Course 1:

* 2500 IU's/m2/day.
* Intramuscular injection (IM) on days 4, 11 and 18.

In Treatment Course 2:

* 2500 IU's/m2/day.
* Intramuscular injection (IM) on day 15. intervention 4: In Treatment Course 1 only:

• 60 mg/m2/day IV over 15 minutes on day 1. intervention 5: * Given Intrathecally on day 1 of course 1 at the dose defined by age below.

  * 30 mg for patients age 1-1.99
  * 50 mg for patients age 2-2.99
  * 70 mg for patients \>3 years of age
* Omit IT Ara-C on Day 1 if patient received IT therapy prior to study enrollment as part of diagnostic lumbar puncture procedure.

In Treatment Course 2: • 75 mg/m2/day IV on days 2 through 5 and days 9 through 12. intervention 6: In Treatment Course 1:

• Given Intrathecally on day 15 at the dose defined by age below.

* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age

In Treatment Course 2:

• Given Intrathecally on day 1, 8, 15 and 22 at the dose defined by age below.

* 8 mg for patients age 1-1.99
* 10 mg for patients age 2-2.99
* 12 mg for patients 3-8.99 years of age
* 15 mg for patients \>9 years of age

In Treatment Course 3:

Intrathecally on day 1 at the age-defined dose intervention 7: Course 2 only: • 1000mg/m2/day IV over 30 minutes to be given on day 1. intervention 8: Treatment Course 2 only: • 60 mg/m2/day to be given orally on days 1 through 14.

Protocol documents: