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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT01406756
Other study ID # AALL1131
Secondary ID NCI-2011-03797CD
Status Recruiting
Phase Phase 3
First received July 29, 2011
Last updated August 23, 2016
Start date February 2012

Study information

Verified date August 2016
Source Children's Oncology Group
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This randomized phase III trial is studying how well combination chemotherapy works in treating young patients with newly diagnosed acute lymphoblastic leukemia that is likely to come back or spread. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.


Description:

PRIMARY OBJECTIVES:

I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance (IM) high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX).

II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm).

SECONDARY OBJECTIVES:

I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL.

II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL.

III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-IMIDM and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality.

IV. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL.

V. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients.

VI. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON.

VII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to 11 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention.

TERTIARY OBJECTIVES:

I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm.

OUTLINE:

INDUCTION THERAPY:

Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1; vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 (plus days 15 and 22 for CNS3 patients). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients are randomized to 1 of 2 treatment arms.

ARM I HR B-ALL CONSOLIDATION (C): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL C: Patients receive Consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C.

INTERIM MAINTENANCE THERAPY:

ARM I HR B-ALL INTERIM MAINTENANCE (IM): Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY:

ARM I HR B-ALL DELAYED INTENSIFICATION (DI): Patients receive DI therapy comprising vincristine sulfate IV over 1 hour on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI.

MAINTENANCE (M) THERAPY:

ARM I HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

ARM II HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

VERY HIGH-RISK B-ALL: Patients are randomized to 1 of 3 treatment arms.

CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY PART II:

ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL C (EXPERIMENTAL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM C VHR B-ALL C: Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (Closed as of 9/12/2014)

INTERIM MAINTENANCE I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION PART II:

ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 15-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL DI (EXPERIMENTAL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM C VHR B-ALL DI: Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014)

INTERIM MAINTENANCE II: In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Rapid early responders (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID or prednisone PO BID on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

Slow early responders (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: All patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-60 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39.

MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for 10 years.


Recruitment information / eligibility

Status Recruiting
Enrollment 4895
Est. completion date
Est. primary completion date August 2021
Accepts healthy volunteers No
Gender Both
Age group 1 Year to 30 Years
Eligibility 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/uL

- 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 World Health Organization [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

- Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction:

- 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 peripheral blood (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 bone marrow (BM) MRD >= 0.01%

- Both NCI standard risk (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:

- Intrachromosomal amplification of chromosome 21 (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 breakpoint cluster region (BCR)-v-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1) fusion (not eligible for post-Induction therapy on this study; non-DS patients may be eligible to enroll in AALL1122 or successor Children's Oncology Group [COG] Philadelphia positive [Ph+] ALL trial by day 15 Induction)

- DS HR B-ALL patients with Induction failure or BCR-ABL1

- Female patients who are pregnant are ineligible

- 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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Clofarabine
Given IV
Cyclophosphamide
Given IV
Cytarabine
Given IT, IV or SC
Dexamethasone
PO or IV
Doxorubicin Hydrochloride
Given IV
Etoposide
Given IV
Hydrocortisone Sodium Succinate
Given IT
Other:
Laboratory Biomarker Analysis
Correlative studies
Drug:
Leucovorin Calcium
Given PO or IV
Mercaptopurine
Given PO
Methotrexate
Given IT and IV
Pegaspargase
Given IV
Prednisone
Given PO or IV
Radiation:
Radiation Therapy
Undergo radiation therapy
Drug:
Thioguanine
Given PO
Vincristine Sulfate
Given IV

Locations

Country Name City State
Australia Monash Medical Center-Clayton Campus Clayton Victoria
Australia Royal Brisbane and Women's Hospital Herston Queensland
Australia Royal Children's Hospital-Brisbane Herston Queensland
Australia John Hunter Children's Hospital Hunter Regional Mail Centre New South Wales
Australia Royal Children's Hospital Parkville Victoria
Australia Princess Margaret Hospital for Children Perth Western Australia
Australia Lady Cilento Children's Hospital South Brisbane Queensland
Canada Alberta Children's Hospital Calgary Alberta
Canada University of Alberta Hospital Edmonton Alberta
Canada IWK Health Centre Halifax Nova Scotia
Canada McMaster Children's Hospital at Hamilton Health Sciences Hamilton Ontario
Canada Cancer Centre of Southeastern Ontario at Kingston General Hospital Kingston Ontario
Canada Children's Hospital London Ontario
Canada The Montreal Children's Hospital of the MUHC Montreal Quebec
Canada Children's Hospital of Eastern Ontario Ottawa Ontario
Canada Allan Blair Cancer Centre Regina Saskatchewan
Canada Janeway Child Health Centre Saint John's Newfoundland and Labrador
Canada Saskatoon Cancer Centre Saskatoon Saskatchewan
Canada Hospital for Sick Children Toronto Ontario
Canada British Columbia Children's Hospital Vancouver British Columbia
Canada CancerCare Manitoba Winnipeg Manitoba
Ireland Our Lady's Children's Hospital Dublin Co Dublin
New Zealand Christchurch Hospital Christchurch
New Zealand Starship Children's Hospital Grafton Auckland
Puerto Rico San Jorge Children's Hospital San Juan
Puerto Rico University Pediatric Hospital San Juan
Switzerland Swiss Pediatric Oncology Group - Geneva Geneva
Switzerland Swiss Pediatric Oncology Group - Lausanne Lausanne
United States Children's Hospital Medical Center of Akron Akron Ohio
United States Albany Medical Center Albany New York
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Texas Tech University Health Science Center-Amarillo Amarillo Texas
United States Providence Alaska Medical Center Anchorage Alaska
United States C S Mott Children's Hospital Ann Arbor Michigan
United States Mission Hospital-Memorial Campus Asheville North Carolina
United States Children's Healthcare of Atlanta - Egleston Atlanta Georgia
United States Georgia Regents University Medical Center Augusta Georgia
United States Children's Hospital Colorado Aurora Colorado
United States Dell Children's Medical Center of Central Texas Austin Texas
United States Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland
United States Sinai Hospital of Baltimore Baltimore Maryland
United States University of Maryland/Greenebaum Cancer Center Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Walter Reed National Military Medical Center Bethesda Maryland
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Children's Hospital of Alabama Birmingham Alabama
United States University of Alabama at Birmingham Cancer Center Birmingham Alabama
United States Saint Luke's Mountain States Tumor Institute Boise Idaho
United States Floating Hospital for Children at Tufts Medical Center Boston Massachusetts
United States Massachusetts General Hospital Cancer Center Boston Massachusetts
United States Montefiore Medical Center - Moses Campus Bronx New York
United States Roswell Park Cancer Institute Buffalo New York
United States University of Vermont College of Medicine Burlington Vermont
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States Medical University of South Carolina Charleston South Carolina
United States West Virginia University Charleston Charleston West Virginia
United States Carolinas Medical Center/Levine Cancer Institute Charlotte North Carolina
United States Novant Health Presbyterian Medical Center Charlotte North Carolina
United States University of Virginia Cancer Center Charlottesville Virginia
United States T C Thompson Children's Hospital Chattanooga Tennessee
United States Lurie Children's Hospital-Chicago Chicago Illinois
United States University of Chicago Comprehensive Cancer Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Cincinnati Children's Hospital Medical Center Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States Rainbow Babies and Childrens Hospital Cleveland Ohio
United States Columbia Regional Columbia Missouri
United States Palmetto Health Richland Columbia South Carolina
United States University of Missouri - Ellis Fischel Columbia Missouri
United States Nationwide Children's Hospital Columbus Ohio
United States Driscoll Children's Hospital Corpus Christi Texas
United States Medical City Dallas Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Geisinger Medical Center Danville Pennsylvania
United States Dayton Children's Hospital Dayton Ohio
United States Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado
United States Blank Children's Hospital Des Moines Iowa
United States Saint John Hospital and Medical Center Detroit Michigan
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Southern California Permanente Medical Group Downey California
United States City of Hope Comprehensive Cancer Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States Michigan State University Clinical Center East Lansing Michigan
United States El Paso Children's Hospital El Paso Texas
United States Inova Fairfax Hospital Falls Church Virginia
United States Sanford Medical Center-Fargo Fargo North Dakota
United States Hurley Medical Center Flint Michigan
United States Broward Health Medical Center Fort Lauderdale Florida
United States Golisano Children's Hospital of Southwest Florida Fort Myers Florida
United States Lee Memorial Health System Fort Myers Florida
United States Cook Children's Medical Center Fort Worth Texas
United States University of Florida Gainesville Florida
United States Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan
United States Saint Vincent Hospital Green Bay Wisconsin
United States BI-LO Charities Children's Cancer Center Greenville South Carolina
United States East Carolina University Greenville North Carolina
United States Greenville Cancer Treatment Center Greenville South Carolina
United States Hackensack University Medical Center Hackensack New Jersey
United States Connecticut Children's Medical Center Hartford Connecticut
United States Penn State Hershey Children's Hospital Hershey Pennsylvania
United States Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida
United States Kapiolani Medical Center for Women and Children Honolulu Hawaii
United States Tripler Army Medical Center Honolulu Hawaii
United States University of Hawaii Cancer Center Honolulu Hawaii
United States Baylor College of Medicine Houston Texas
United States M D Anderson Cancer Center Houston Texas
United States Riley Hospital for Children Indianapolis Indiana
United States Saint Vincent Hospital and Health Care Center Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States University of Mississippi Medical Center Jackson Mississippi
United States Nemours Children's Clinic-Jacksonville Jacksonville Florida
United States Bronson Methodist Hospital Kalamazoo Michigan
United States The Childrens Mercy Hospital Kansas City Missouri
United States East Tennessee Childrens Hospital Knoxville Tennessee
United States Children's Specialty Center of Nevada II Las Vegas Nevada
United States Nevada Cancer Research Foundation CCOP Las Vegas Nevada
United States Summerlin Hospital Medical Center Las Vegas Nevada
United States Sunrise Hospital and Medical Center Las Vegas Nevada
United States University Medical Center of Southern Nevada Las Vegas Nevada
United States Dartmouth Hitchcock Medical Center Lebanon New Hampshire
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Arkansas Children's Hospital Little Rock Arkansas
United States University of Arkansas for Medical Sciences Little Rock Arkansas
United States Saint Barnabas Medical Center Livingston New Jersey
United States Loma Linda University Medical Center Loma Linda California
United States Miller Children's and Women's Hospital Long Beach Long Beach California
United States Cedars-Sinai Medical Center Los Angeles California
United States Children's Hospital Los Angeles Los Angeles California
United States Mattel Children's Hospital UCLA Los Angeles California
United States Kosair Children's Hospital Louisville Kentucky
United States Covenant Children's Hospital Lubbock Texas
United States Children's Hospital Central California Madera California
United States University of Wisconsin Hospital and Clinics Madison Wisconsin
United States Marshfield Clinic Marshfield Wisconsin
United States Loyola University Medical Center Maywood Illinois
United States Vannie Cook Children's Clinic McAllen Texas
United States Cardon Children's Medical Center Mesa Arizona
United States Baptist Hospital of Miami Miami Florida
United States Nicklaus Children's Hospital Miami Florida
United States University of Miami Miller School of Medicine-Sylvester Cancer Center Miami Florida
United States Midwest Children's Cancer Center Milwaukee Wisconsin
United States Winthrop University Hospital Mineola New York
United States Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota
United States University of Minnesota/Masonic Cancer Center Minneapolis Minnesota
United States University of South Alabama Mobile Alabama
United States West Virginia University Healthcare Morgantown West Virginia
United States Morristown Medical Center Morristown New Jersey
United States Vanderbilt University/Ingram Cancer Center Nashville Tennessee
United States Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey
United States Saint Peter's University Hospital New Brunswick New Jersey
United States Yale University New Haven Connecticut
United States The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York
United States Children's Hospital New Orleans New Orleans Louisiana
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Tulane University Health Sciences Center New Orleans Louisiana
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Mount Sinai Medical Center New York New York
United States Weill Medical College of Cornell University New York New York
United States Newark Beth Israel Medical Center Newark New Jersey
United States Childrens Hospital-King's Daughters Norfolk Virginia
United States Advocate Children's Hospital-Oak Lawn Oak Lawn Illinois
United States Children's Hospital and Research Center at Oakland Oakland California
United States Kaiser Permanente-Oakland Oakland California
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Children's Hospital and Medical Center of Omaha Omaha Nebraska
United States University of Nebraska Medical Center Omaha Nebraska
United States Children's Hospital of Orange County Orange California
United States Arnold Palmer Hospital for Children Orlando Florida
United States Florida Hospital Orlando Orlando Florida
United States Nemours Children's Clinic - Orlando Orlando Florida
United States Nemours Children's Hospital Orlando Florida
United States UF Cancer Center at Orlando Health Orlando Florida
United States Lucile Packard Children's Hospital Stanford University Palo Alto California
United States Advocate Children's Hospital-Park Ridge Park Ridge Illinois
United States Advocate Lutheran General Hospital Park Ridge Illinois
United States Saint Joseph's Regional Medical Center Paterson New Jersey
United States Nemours Children's Clinic - Pensacola Pensacola Florida
United States Saint Jude Midwest Affiliate Peoria Illinois
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Saint Christopher's Hospital for Children Philadelphia Pennsylvania
United States Phoenix Childrens Hospital Phoenix Arizona
United States Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania
United States Legacy Emanuel Children's Hospital Portland Oregon
United States Oregon Health and Science University Portland Oregon
United States Naval Medical Center - Portsmouth Portsmouth Virginia
United States Rhode Island Hospital Providence Rhode Island
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Carilion Clinic Children's Hospital Roanoke Virginia
United States Mayo Clinic Rochester Minnesota
United States University of Rochester Rochester New York
United States Beaumont Children's Hospital-Royal Oak Royal Oak Michigan
United States William Beaumont Hospital-Royal Oak Royal Oak Michigan
United States Sutter General Hospital Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Cardinal Glennon Children's Medical Center Saint Louis Missouri
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Washington University School of Medicine Saint Louis Missouri
United States All Children's Hospital Saint Petersburg Florida
United States Primary Children's Hospital Salt Lake City Utah
United States Children's Hospital of San Antonio San Antonio Texas
United States Methodist Children's Hospital of South Texas San Antonio Texas
United States University of Texas Health Science Center at San Antonio San Antonio Texas
United States Naval Medical Center -San Diego San Diego California
United States Rady Children's Hospital - San Diego San Diego California
United States UCSF Medical Center-Mission Bay San Francisco California
United States UCSF Medical Center-Parnassus San Francisco California
United States Santa Barbara Cottage Hospital Santa Barbara California
United States Memorial University Medical Center Savannah Georgia
United States Maine Children's Cancer Program Scarborough Maine
United States Seattle Children's Hospital Seattle Washington
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington
United States Baystate Medical Center Springfield Massachusetts
United States Southern Illinois University School of Medicine Springfield Illinois
United States Stony Brook University Medical Center Stony Brook New York
United States Overlook Hospital Summit New Jersey
United States State University of New York Upstate Medical University Syracuse New York
United States Madigan Army Medical Center Tacoma Washington
United States Mary Bridge Children's Hospital and Health Center Tacoma Washington
United States Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida
United States Tampa General Hospital Tampa Florida
United States Scott and White Memorial Hospital Temple Texas
United States Mercy Children's Hospital Toledo Ohio
United States The Toledo Hospital/Toledo Children's Hospital Toledo Ohio
United States Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center Torrance California
United States The University of Arizona Medical Center-University Campus Tucson Arizona
United States Natalie Warren Bryant Cancer Center at Saint Francis Tulsa Oklahoma
United States New York Medical College Valhalla New York
United States Children's National Medical Center Washington District of Columbia
United States MedStar Georgetown University Hospital Washington District of Columbia
United States Saint Mary's Hospital West Palm Beach Florida
United States Alfred I duPont Hospital for Children Wilmington Delaware
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States University of Massachusetts Medical School Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
Children's Oncology Group National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Ireland,  New Zealand,  Puerto Rico,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Other Change in the MRD from end-Induction to end-Consoldiation Whether the reduction of MRD from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arms 1 and/or 2 compared to the Control Arm will be determined. Baseline to up to 10 years No
Primary Comparison of DFS of children with HR B-ALL receiving post-Induction age adjusted ITT on an MBFM-IMHDM backbone compared to age adjusted IT MTX Compared using 2-sided log rank test, alpha = 5%. At 5 years No
Primary DFS of children, adolescents, and young adults with VHR B-ALL between arms DFS of children, adolescents, and young adults with VHR B-ALL will be compared in all arms using 1-sided log rank test, alpha 0.025. At 4 years No
Secondary Increase of greater than or equal to 65% of 5-year DFS and less than 10% induction mortality in patients with DS and HR B-ALL treated with modified Induction and post-Induction therapy regimen with MBFM-IMIDM At 5 years No
Secondary OS rate for HR B-ALL patients Compared informally between arms. At 5 years No
Secondary OS rate for VHR B-ALL patients Compared informally between arms. At 4 years No
Secondary Percentage of VHR-ALL patients randomized to control versus experimental arms that attain MRD less than or equal to 0.01% upon recovery from consolidation Compared between control vs experimental arms. Week 13-14 No
Secondary Toxicity and tolerability of Experimental arm and Control arm in patients with VHR B-ALL Graded using the Version 4.0 CTCAE of the NCI. Up to 10 years Yes
Secondary Toxicity and tolerability of MBFM-IMIDM in children with Down syndrome Graded using the Version 4.0 CTCAE of the NCI. Up to 10 years Yes
Secondary Toxicity and tolerability of post-induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL Graded using the Version 4.0 Common Terminology Criteria for Adverse Events (CTCAE) of the NCI. Up to 10 years Yes
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