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Recurrent Pediatric ALLPhase 1/2NCT00439296

ABT-751 With Chemotherapy for Relapsed Pediatric ALL

A Phase 1/2 study testing ABT-751, Dexamethasone and PEG-asparaginase in people with Recurrent Pediatric ALL and Relapsed Pediatric ALL, run by Therapeutic Advances in Childhood Leukemia Consortium at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages Up to 21 years
What is being tested?
ABT-751, Dexamethasone and PEG-asparaginase
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
5 sitesUnited States
Study dates
22 May 2006to 23 Sep 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Age Patients must be < 21 years of age when enrolled onto this study. T2005-001 Protocol version 6/27/2007 17
  • Diagnosis
  • Patients must have relapsed or refractory ALL with a M3 marrow (marrow blasts >25%) without clinical evidence of testicular disease or laboratory evidence of CNS disease defined as CSF WBC > 5 cells/microliter and blasts. (See Appendix I for method of evaluating traumatic lumbar punctures.) Patients in early first relapse (defined as a patient who relapses less than 36 months from their initial remission [CR1]) are eligible for the phase I portion of the trial.
  • Performance Level Karnofsky > 60% for patients > 10 years of age and Lansky > 60% for patients < 10 years of age.
  • Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
  • Prior anthracycline exposure: Patients must have less than 300mg/m2 lifetime exposure of anthracycline chemotherapy. (See Appendix III for calculation criteria)
Show all 17Show fewer
  • Stem Cell Transplant (SCT): Patients are eligible 6 months after allogeneic stem cell transplant as long as patients are not actively being treated for graft-versus-host-disease (GvHD).
  • During the phase I portion of the trial, there is no limit on the number of prior treatment regimens.
  • During the phase II portion of the trial, patients must have had two or more prior therapeutic attempts defined as:
  • Persistent initial disease after two induction attempts, or
  • Relapse after one-reinduction attempt (2nd relapse), or
  • Persistent disease after first relapse and initial re-induction attempt (Patients in any first relapse are not eligible for the phase II portion of the study)
  • During the phase II portion of the trial, patients must have no more than 3 prior therapeutic attempts and it must be at least 6 months since the last treatment with a "VPLD" induction/re-induction regimen.
  • Reproductive Function
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment and within 48 hours of starting therapy.
  • Female patients with infants must agree not to breastfeed their infants while on this study.
  • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for 3 months following completion of therapy.

Who cannot join

  • Drug Allergies
  • Patients will be excluded if they have allergies to the following drugs:
  • Asparaginase products
  • Sulfa containing medications
  • Renal Function Patients will be excluded if their serum creatinine is > the upper limit of normal (ULN) for age at the institution's laboratory.
  • Liver/Pancreatic Function
Show all 21Show fewer
  • Direct bilirubin > 1.5x the institutional ULN for age. A total bilirubin result that is less than 1.5 times the institutional ULN for age may be used for eligibility if a direct bilirubin result is not available.
  • SGPT (ALT) > 4 x institutional ULN
  • Grade 3 or greater pancreatitis as defined by the CTCAE v3.0
  • Amylase or Lipase > 2 x institutional ULN
  • Cardiac Function Patients will be excluded if their shortening fraction by echocardiogram is less than 30%.
  • Infection Patients will be excluded if they have an active, uncontrolled infection.
  • Patients with grade 2 or greater motor or sensory neuropathy per CTC 3.0 criteria.
  • Patients with grade 2 or greater Ileus (neuroconstipation) per CTC 3.0 criteria.
  • Patients currently being treated with coumadin.
  • Patients currently being treated with colchicines.
  • Patients planning on receiving other investigational agents while on this study. (An investigational agent is defined as any drug not currently approved for use in humans.)
  • Patients planning on receiving other anti-cancer therapies while on this study.
  • Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
  • Patients who, based on BSA and current dose level, require a daily dose of ABT-751 that is less than 25mg per day.
  • Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT Ara-C or IT MTX were given within 48 hours of study enrollment as part of the diagnostic lumbar procedure. These patients will not participate in the CSF PK portion of the study.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • C.S. Mott Children's Hospital

    Ann Arbor, Michigan, 48109-0914

  • Childrens Hospital Los Angeles

    Los Angeles, California, 90027

  • Stanford University Medical Center

    Palo Alto, California, 94304-1812

  • UCSF School of Medicine

    San Francisco, California, 94143-0106

  • Seattle Children's Hospital

    Seattle, Washington, 98105

Other trials in United States

About this study

Official title: A Phase I/II Trial of ABT-751 Combined With Dexamethasone, PEG-asparaginase, and Doxorubicin in Relapsed Acute Lymphoblastic Leukemia (ALL)

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.

Read the 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.

Being tested
ABT-751, Dexamethasone, PEG-asparaginase, Doxorubicin, Cytarabine
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
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ABT-751Drug

    Also called Antineoplastics

    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.

  • DexamethasoneDrug

    Also called Decadron, Dexasone, Diodex, Hexadrol

    In Treatment Course 1 only:

    • 10 mg/m2/day divided BID.
    • Take dexamethasone by mouth days 1-14.

  • PEG-asparaginaseDrug

    Also called Elspar, Kidrolase, L-asparaginase, Erwinia L-asparaginase

    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.

  • DoxorubicinDrug

    Also called Adriamycin, Rubex

    In Treatment Course 1 only:

    • 60 mg/m2/day IV over 15 minutes on day 1.

  • CytarabineDrug

    Also called Cytosar-U, Ara-C, Arabinosylcytosine

    • 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.

  • MethotrexateDrug

    Also called Otrexup, Rasuvo, Rheumatrex, Trexall

    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

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    Course 2 only: • 1000mg/m2/day IV over 30 minutes to be given on day 1.

  • 6-thioguanineDrug

    Also called Thioguanine Tabloid, 6-TG, 2-Amino-6-Mercaptopurine

    Treatment Course 2 only: • 60 mg/m2/day to be given orally on days 1 through 14.

Study groups in NCT00439296
Study groupRoleWhat they receive
Dose Level 1ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level 2ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level 3ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level 4ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level 5ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level 0ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine
Dose Level -1ExperimentalTreatment 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
Receives: Drug: ABT-751; Drug: Dexamethasone; Drug: PEG-asparaginase; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Cyclophosphamide; Drug: 6-thioguanine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients That Experienced Dose Limiting Toxicity From ABT-751

    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

    Measured: Each dose level is evaluated

  2. Number of Patients That Achieved Complete Response to ABT-751

    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.

    Measured: Day 29 of Course 1

Secondary outcomes (1)

  1. Number of Patients With Occurrence of Toxic Death

    The occurrence of toxic death at anytime that is definitely, probably or possibly related to the treatment.

    Measured: From the first dose of study therapy until 30 days after last therapy dose. Last dose protocol therapy is on day 21.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2007 (estimated)
  2. Study start22 May 2006
  3. Primary completion19 May 2009
  4. Study completion23 Sep 2009

Why it stopped: The study was stopped due to poor accrual and lack of funding.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00439296
Sponsor's protocol ID
T2005-001
Status last verified
Feb 2021
First submitted
21 Feb 2007
Last updated
17 Mar 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing ABT-751, Dexamethasone and PEG-asparaginase in people with Recurrent Pediatric ALL and Relapsed Pediatric ALL, run by Therapeutic Advances in Childhood Leukemia Consortium at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 17 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients That Experienced Dose Limiting Toxicity From ABT-751 (time frame: Each dose level is evaluated). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00439296.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2021.

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