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Clinical Trial COGAALL1131

Title

A Phase III Randomized Trial for Newly Diagnosed High Risk B-precursor Acute Lymphoblastic Leukemia (ALL) Testing Clofarabine (IND #73789, NSC# 606869) in the Very High Risk Stratum

Principal Investigator(s)

Haydar Frangoul

Details

  • Protocol No. COGAALL1131
  • Open Date: 04/05/2012
  • Staging: Phase III
  • Age Group: Both Child and Adult
  • Scope: National
  • Objective: - To determine if the administration of post-Induction age adjusted ITT on an MBFM-IMHDM backbone will improve 5-year DFS of children with HR-ALL compared to age adjusted IT MTX. - To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) or the clofarabine + cyclophosphamide + etoposide combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with VHR-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). - To determine, in a randomized fashion, if the cyclophosphamide + etoposide + clofarabine containing combination regimen (Experimental Arm 2) will improve the 4-year DFS of children, adolescents, and young adults with VHR-ALL compared to the cyclophosphamide + etoposide combination regimen (Experimental Arm 1).
  • Disease Sites: Leukemia; Pediatric Leukemia
  • Therapies: Chemotherapy - cytotoxic; Radiotherapy; Therapy (NOS)
  • Drugs: 6-thioguanine (6-TG); Clofarabine; Cyclophosphamide (CTX); Cytarabine (ARA-C); Dexamethasone; Dosorubicin; Doxorubicin; Etoposide; G-CSF; Hydrocortisone; Levoleucovorin; Mercaptopurine; Methotrexate; Pegaspargase (Oncaspar); Prednisone; Vincristine
  • Participating Institutions: Vanderbilt University
  • National Clinical Trial ID: NCT01406756
  • Secondary Protocol No: Not Specified

Description

None Provided.

Eligibility

Ages Eligible for Study:1 Year to 30 Years
Genders Eligible for Study:Both
Accepts Healthy Volunteers:No

Criteria

Inclusion Criteria:
• Patients must be enrolled on AALL08B1 prior to enrollment on AALL1131
• White Blood Cell Count (WBC) Criteria
• Age 1-9.99 years: WBC >= 50 000/μL
• Age 10-30.99 years: Any WBC
• Age 1-30.99 years: Any WBC with:
• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment
• Patients must have newly diagnosed B lymphoblastic leukemia (2008 WHO classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
• Eligibility criteria for the Incidence and Natural History of Osteonecrosis study
• Patients must be 10 years of age or greater at the time of B-ALL diagnosis, enrolled on AALL1131
• Patients with Down syndrome are not eligible
• Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study
• Patients must be aged 6 to 11 years at time of B-ALL diagnosis, enrolled on AALL1131
• Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)
• Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation)
• Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
• Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the HR B-ALL stratum of this study at the end of Induction:
• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with Day 8 PB minimal residual disease (MRD) >= 1% and Day 29 BM MRD < 0.01%
• With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any Day 8 PB MRD and Day 29 BM MRD > 0.01%
• Both NCI SR and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria, will be eligible for the HR stratum
• Patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the VHR B-ALL stratum of this study at the end of Induction:
• iAMP21
• Mixed-lineage leukemia (MLL) rearrangement
• Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)
• Induction Failure (M3 BM at Day 29)
• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with Day 29 BM MRD > 0.01%
• Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction:
• Day 29 MRD >= 0.01%
• MLL rearrangement
• Hypodiploidy (n< 45 chromosomes and/or DNA index < 0.81)
• DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction Failure (M3 BM Day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met
Exclusion Criteria:
• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131
• Patients with BCR-ABL1 fusion (not eligible for post-Induction therapy on this study; non-DS patients may be eligible to enroll in AALL1122 or successor COG Ph+ ALL trial by Day 15 Induction)
• DS HR B-ALL patients with Induction failure or BCR-ABL1
• Direct bilirubin > 1.5 x upper limit of normal (ULN) for age
• Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) > 3 x upper limit of normal (ULN) for age
• Lipase > 2.0 x upper limit of normal (ULN) for age
• Creatinine clearance or radioisotope GFR < 70 mL/min/1.73 m^2
• A serum creatinine based on age/gender as follows:
• 1 month to < 6 months = 0.4 (male) and 0.4 (female)
• 6 months to < 1 year = 0.5 (male) and 0.5 (female)
• 1 to < 2 years = 0.6 (male) and 0.6 (female)
• 2 to < 6 years = 0.8 (male) and 0.8 (female)
• 6 to < 10 years = 1 (male) and 1 (female)
• 10 to < 13 years = 1.2 (male) and 1.2 (female)
• 13 to < 16 years = 1.5 (male) and 1.4 (female)
• >= 16 years = 1.7 (male) and 1.4 (female)
• VHR B-ALL patients with known Hepatitis B or C infection or history of cirrhosis at the time of post-Induction randomization
• Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
• Lactating females are not eligible unless they have agreed not to breastfeed their infant
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation