A Phase 1/2 interventional study of ABT-751 and Dexamethasone in Recurrent Pediatric ALL, Relapsed Pediatric ALL and Acute Lymphoblastic Leukemia, sponsored by Therapeutic Advances in Childhood Leukemia Consortium. Terminated at 5 sites in United States. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2021-03-17.
Sponsored by Therapeutic Advances in Childhood Leukemia Consortium · Phase 1/2, Interventional, and Treatment
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.
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.
5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.
This study's enrollment of 9 is below the median of 38 across 4,247 interventional studies indexed under Leukemia.
Browse Leukemia studies →Therapeutic Advances in Childhood Leukemia Consortium is the lead sponsor of 21 studies on the registry; 3 are open to participants now.
Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
During the phase II portion of the trial, patients must have had two or more prior therapeutic attempts defined as:
Reproductive Function
Exclusion Criteria
Drug Allergies
Patients will be excluded if they have allergies to the following drugs:
Liver/Pancreatic Function
Infection Patients will be excluded if they have an active, uncontrolled infection.
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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 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
Drug: ABT-751 · Drug: Dexamethasone · Drug: PEG-asparaginase · Drug: Doxorubicin · Drug: Cytarabine · Drug: Methotrexate · Drug: Cyclophosphamide · Drug: 6-thioguanine
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.
Also known as: Antineoplastics
In Treatment Course 1 only: * 10 mg/m2/day divided BID. * Take dexamethasone by mouth days 1-14.
Also known as: Decadron, Dexasone, Diodex, Hexadrol, Maxidex
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.
Also known as: Elspar, Kidrolase, L-asparaginase, Erwinia L-asparaginase
In Treatment Course 1 only: • 60 mg/m2/day IV over 15 minutes on day 1.
Also known as: Adriamycin, Rubex
* 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.
Also known as: Cytosar-U, Ara-C, Arabinosylcytosine
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
Also known as: Otrexup, Rasuvo, Rheumatrex, Trexall, Amethopterin, Methotrexate Sodium, MTX
Course 2 only: • 1000mg/m2/day IV over 30 minutes to be given on day 1.
Also known as: Cytoxan, Neosar
Treatment Course 2 only: • 60 mg/m2/day to be given orally on days 1 through 14.
Also known as: Thioguanine Tabloid, 6-TG, 2-Amino-6-Mercaptopurine
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
Time frame: Each dose level is evaluated
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.
Time frame: Day 29 of Course 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.
Time frame: From the first dose of study therapy until 30 days after last therapy dose. Last dose protocol therapy is on day 21.
| Milestone | Dose Level 1 | Dose Level 0 |
|---|---|---|
| Started | 5 | 4 |
| Treatment course 1 | 5 | 3 |
| Treatment course 2 | 1 | 1 |
| Completed | 5 | 4 |
| Not completed | 0 | 0 |
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
| Participants | Dose Level 1 | Dose Level 0 |
|---|---|---|
| # of patients with DLT | 2 | 0 |
| # of patients without DLT | 3 | 4 |
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.
| Participants | Dose Level 1 | Dose Level 0 |
|---|---|---|
| # of patients not achieving complete response | 4 | 1 |
| # of patients who achieved complete response | 1 | 3 |
The occurrence of toxic death at anytime that is definitely, probably or possibly related to the treatment.
| Participants | Dose Level 1 | Dose Level 0 |
|---|---|---|
| # of patients that experienced toxic death | 0 | 0 |
| # of patients that did not experience toxic death | 5 | 4 |
Collected over Adverse events and serious adverse events will be collected and reported on the electronic case report forms beginning with the first dose of investigational product until 30 days following the last dose of ABT-751, whether elicited or spontaneously reported by the patient, up to day 51 days (30 days after day 21, last day of the protocol therapy).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose Level 1 | 4/5 (80%) | 5/5 (100%) | 5/5 (100%) |
| Dose Level 0 | 0/4 (0%) | 4/4 (100%) | 4/4 (100%) |
| Event | Dose Level 1 | Dose Level 0 |
|---|---|---|
| Infection w/ Gr 3/4 ANC, BloodInfections and infestations | 4/5 | 1/4 |
| Febrile neutropeniaBlood and lymphatic system disorders | 1/5 | 3/4 |
| Bone painMusculoskeletal and connective tissue disorders | 0/5 | 1/4 |
| Infection w/ Gr 3/4 ANC, SkinInfections and infestations | 1/5 | 1/4 |
| AnorexiaMetabolism and nutrition disorders | 1/5 | 0/4 |
| DehydrationGastrointestinal disorders | 1/5 | 0/4 |
| Diarrhea NOSGastrointestinal disorders | 1/5 | 0/4 |
| Hyperglycemia NOSMetabolism and nutrition disorders | 1/5 | 0/4 |
| Ileus paralyticGastrointestinal disorders | 1/5 | 0/4 |
| Infection w/ Gr 3/4 ANC, NoseInfections and infestations | 1/5 | 0/4 |
| Event | Dose Level 1 | Dose Level 0 |
|---|---|---|
| Alanine aminotransferase increasedInvestigations | 5/5 | 4/4 |
| Blood/Bone Marrow-OtherBlood and lymphatic system disorders | 5/5 | 4/4 |
| ConstipationGastrointestinal disorders | 5/5 | 4/4 |
| HaemoglobinBlood and lymphatic system disorders | 4/5 | 4/4 |
| HeadacheNervous system disorders | 5/5 | 4/4 |
| Hyperglycemia NOSMetabolism and nutrition disorders | 3/5 | 4/4 |
| HypomagnesemiaMetabolism and nutrition disorders | 5/5 | 1/4 |
| HyponatraemiaMetabolism and nutrition disorders | 5/5 | 4/4 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 5/5 | 4/4 |
| Ileus paralyticGastrointestinal disorders | 4/5 | 4/4 |
| Age, Categorical(Participants) | Dose Level 1 | Dose Level 0 | Total |
|---|---|---|---|
| <=18 years | 4 | 3 | 7 |
| Between 18 and 65 years | 1 | 1 | 2 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Dose Level 1 | Dose Level 0 | Total |
|---|---|---|---|
| Female | 2 | 2 | 4 |
| Male | 3 | 2 | 5 |
| Ethnicity (NIH/OMB)(Participants) | Dose Level 1 | Dose Level 0 | Total |
|---|---|---|---|
| Hispanic or Latino | 3 | 2 | 5 |
| Not Hispanic or Latino | 2 | 1 | 3 |
| Unknown or Not Reported | 0 | 1 | 1 |
| Race (NIH/OMB)(Participants) | Dose Level 1 | Dose Level 0 | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 1 | 1 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 4 | 3 | 7 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 1 | 0 | 1 |
This study is terminated, as verified in Feb 2021. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Therapeutic Advances in Childhood Leukemia Consortium