NCT02101853 · CITED IN SOURCE DOCUMENTS

Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-07-29

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Disease Free Survival (DFS) of High-risk (HR) and Intermediate-risk (IR) Relapse Patients

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outcome · POSTED

Disease Free Survival (DFS) of Low Risk (LR) Relapse Patients

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outcome · POSTED

Overall Survival (OS) of HR and IR Relapse Patients

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outcome · POSTED

Overall Survival (OS) of LR Relapse Patients

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outcome · NOT POSTED

Rates of Minimal Residual Disease (MRD) Positivity (> 0.01%)

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outcome · NOT POSTED

Hematologic Complete Remission Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)

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outcome · NOT POSTED

MRD Negativity (< 0.01%) Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)

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outcome · NOT POSTED

Proportion of Patients That Proceed to Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab (for Treatment Failure Patients Not Previously Receiving Blinatumomab)

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outcome · NOT POSTED

Feasibility of Rapid Taper of Immune Suppression for Subset of HSCT Patients With MRD >= 0.01% Pre- and/or Post-HSCT With no Acute Graft Versus Host Disease (aGVHD)

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outcome · NOT POSTED

Safety of Rapid Taper of Immune Suppression for Subset of HSCT Patients With MRD >= 0.01% Pre- and/or Post-HSCT With no aGVHD Defined as < 5% Rate of Treatment-related Mortality (TRM)

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outcome · NOT POSTED

Blinatumomab Pharmacokinetics (PK)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Patients \>= 1 year and \< 31 years of age at the time of relapse will be eligible * First relapse of B-ALL, allowable sites of disease include isolated bone marrow, combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular; extramedullary sites are limited to the CNS and testicles * No waiting period for patients who relapse while receiving standard maintenance therapy * Patients who relapse on frontline therapy in phases other than maintenance must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study * Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the exception of hydroxyurea, which is permitted up to 24 hours prior to the start of protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy (methotrexate strongly preferred) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status * Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur * Stem cell transplant or rescue: patient has not had a prior stem cell transplant or rescue * Patient has not had prior treatment with blinatumomab * With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse) * Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age * Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a serum creatinine based on age/gender as follows: * 1 to \< 2 years: =\< 0.6 mg/dL * 2 to \< 6 years: =\< 0.8 mg/dL * 6 to \< 10 years: =\< 1 mg/dL * 10 to \< 13 years: =\< 1.2 mg/dL * 13 to \< 16 years: =\< 1.5 mg/dL (males) and =\< 1.4 mg/dL (females) * \>= 16 years: =\< 1.7 mg/dL (males) and =\< 1.4 mg/dL (females) * Direct bilirubin \< 3.0 mg/dL * Shortening fraction of \>= 27% by echocardiogram, or * Ejection fraction of \>= 50% by radionuclide angiogram * All patients and/or their parent or legal guardian must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: * Patients with Philadelphia chromosome positive/breakpoint cluster region protein (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible * Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible * Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not eligible * Patients with B-lymphoblastic lymphoma (B-LL) are not eligible * Patients with known optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal involvement * Patients known to have one of the following concomitant genetic syndromes: Down syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome * Patients with known human immunodeficiency virus (HIV) infection * Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and etoposide phosphate (Etopophos) * Lactating females who plan to breastfeed * Patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs; a pregnancy test is required for female patients of childbearing potential * Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation * Patients with pre-existing significant central nervous system pathology that would preclude treatment with blinatumomab, including: history of severe brain injury, dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement disorder, or autoimmune disease with CNS involvement are not eligible; patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved) * Patients with uncontrolled seizure disorder are not eligible; (patients with seizure disorders that do not require antiepileptic drugs, or are well controlled with stable doses of antiepileptic drugs remain eligible)
healthy Volunteers: false
maximum Age: 31 Years
minimum Age: 1 Year
sex: ALL
std Ages: CHILD
ADULT

Treatment arms and interventions

arm Groups

description
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.
intervention Names
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Drug: Asparaginase
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Etoposide
Drug: Leucovorin Calcium
Drug: Methotrexate
Drug: Mitoxantrone
Drug: Mitoxantrone Hydrochloride
Drug: Pegaspargase
Other: Pharmacological Study
label
Arm A (HR and IR control)
type
ACTIVE_COMPARATOR
description
Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.
intervention Names
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Biological: Blinatumomab
Drug: Cytarabine
Drug: Dexamethasone
Drug: Methotrexate
Other: Pharmacological Study
Drug: Therapeutic Hydrocortisone
label
Arm B (HR and IR blinatumomab)
type
EXPERIMENTAL
description
Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.
intervention Names
Drug: Asparaginase
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Etoposide
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Other: Pharmacological Study
Radiation: Radiation Therapy
Drug: Therapeutic Hydrocortisone
label
Arm C (LR control)
type
ACTIVE_COMPARATOR
description
Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance.
intervention Names
Biological: Blinatumomab
Drug: Cyclophosphamide
Drug: Cytarabine
Drug: Dexamethasone
Drug: Etoposide
Drug: Leucovorin Calcium
Drug: Mercaptopurine
Drug: Methotrexate
Drug: Pegaspargase
Other: Pharmacological Study
Radiation: Radiation Therapy
Drug: Therapeutic Hydrocortisone
label
Arm D (LR blinatumomab)
type
EXPERIMENTAL

interventions

arm Group Labels
Arm A (HR and IR control)
Arm B (HR and IR blinatumomab)
description
Undergo allogeneic HSCT
name
Allogeneic Hematopoietic Stem Cell Transplantation
other Names
Allogeneic
Allogeneic Hematopoietic Cell Transplantation
Allogeneic Stem Cell Transplantation
HSC
HSCT
Stem Cell Transplantation, Allogeneic
type
PROCEDURE
arm Group Labels
Arm A (HR and IR control)
Arm C (LR control)
description
Given IM or IV
name
Asparaginase
other Names
ASP-1
Asparaginase II
Asparaginase-E.Coli
Colaspase
Elspar
Kidrolase
L-Asnase
L-ASP
L-Asparaginase
L-Asparagine Amidohydrolase
Laspar
Lcf-ASP
type
DRUG
arm Group Labels
Arm B (HR and IR blinatumomab)
Arm D (LR blinatumomab)
description
Given IV
name
Blinatumomab
other Names
AMG 103
AMG-103
AMG103
Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
Blincyto
MEDI 538
MEDI-538
MEDI538
MT 103
MT-103
MT103
type
BIOLOGICAL
arm Group Labels
Arm A (HR and IR control)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given IV
name
Cyclophosphamide
other Names
(-)-Cyclophosphamide
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Asta B 518
B 518
B-518
B518
Carloxan
Ciclofosfamida
Ciclofosfamide
Cicloxal
Clafen
Claphene
type
DRUG
arm Group Labels
Arm A (HR and IR control)
Arm B (HR and IR blinatumomab)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given IT and IV or SC
name
Cytarabine
other Names
.beta.-Cytosine arabinoside
1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-.beta.-D-Arabinofuranosylcytosine
1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
1-Beta-D-arabinofuranosylcytosine
1.beta.-D-Arabinofuranosylcytosine
2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
Alexan
Ara-C
ARA-cell
Arabine
type
DRUG
arm Group Labels
Arm A (HR and IR control)
Arm B (HR and IR blinatumomab)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given PO or IV
name
Dexamethasone
other Names
Aacidexam
Adexone
Aknichthol Dexa
Alba-Dex
Alin
Alin Depot
Alin Oftalmico
Amplidermis
Anemul mono
Auricularum
Auxiloson
Baycadron
type
DRUG
arm Group Labels
Arm A (HR and IR control)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given IV
name
Etoposide
other Names
Demethyl Epipodophyllotoxin Ethylidine Glucoside
EPEG
Lastet
Toposar
Vepesid
VP 16
VP 16-213
VP 16213
VP-16
VP-16-213
VP-16213
VP16
type
DRUG
arm Group Labels
Arm A (HR and IR control)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given IV or PO
name
Leucovorin Calcium
other Names
Adinepar
Calcifolin
Calcium (6S)-Folinate
Calcium Folinate
Calcium Leucovorin
Calfolex
Calinat
Cehafolin
Citofolin
Citrec
Citrovorum Factor
Cromatonbic Folinico
type
DRUG
arm Group Labels
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given PO
name
Mercaptopurine
other Names
3H-Purine-6-thiol
6 MP
6 Thiohypoxanthine
6 Thiopurine
6-Mercaptopurine
6-Mercaptopurine Monohydrate
6-MP
6-Purinethiol
6-Thiopurine
6-Thioxopurine
6H-Purine-6-thione, 1,7-dihydro- (9CI)
7-Mercapto-1,3,4,6-tetrazaindene
type
DRUG
arm Group Labels
Arm A (HR and IR control)
Arm B (HR and IR blinatumomab)
Arm C (LR control)
Arm D (LR blinatumomab)
description
Given IT, IV, and PO
name
Methotrexate
other Names
Abitrexate
Alpha-Methopterin
Amethopterin
Brimexate
CL 14377
CL-14377
Emtexate
Emthexat
Emthexate
Farmitrexat
Fauldexato
Folex
type
DRUG
arm Group Labels
Arm A (HR and IR control)
description
Given IV
name
Mitoxantrone
other Names
Dihydroxyanthracenedione
Mitozantrone
type
DRUG
arm Group Labels
Arm A (HR and IR control)
description
Given IV
name
Mitoxantrone Hydrochloride
other Names
CL 232315
DHAD
DHAQ
Dihydroxyanthracenedione Dihydrochloride
Mitoxantrone Dihydrochloride
Mitoxantroni Hydrochloridum
Mitozantrone Hydrochloride
Mitroxone
Neotalem
Novantrone
Onkotrone
Pralifan
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 669
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
The rates at the end of Block 2 and Block 3 will be calculated for the randomized arms for HR and IR relapse patients.
measure
Rates of Minimal Residual Disease (MRD) Positivity (> 0.01%)
time Frame
Up to 12 weeks
description
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
measure
Hematologic Complete Remission Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)
time Frame
Up to 12 weeks
description
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
measure
MRD Negativity (< 0.01%) Rate (for Treatment Failure Patients Not Previously Receiving Blinatumomab)
time Frame
Up to 12 weeks
description
The observed rate will be calculated among patients with treatment failure who did not previously receive blinatumomab.
measure
Proportion of Patients That Proceed to Hematopoietic Stem Cell Transplant (HSCT) After Treatment With Blinatumomab (for Treatment Failure Patients Not Previously Receiving Blinatumomab)
time Frame
Up to 12 weeks
description
The observed rate of grade III-IV aGVHD among this subset will be calculated with 95% confidence intervals and compared descriptively to target rate.
measure
Feasibility of Rapid Taper of Immune Suppression for Subset of HSCT Patients With MRD >= 0.01% Pre- and/or Post-HSCT With no Acute Graft Versus Host Disease (aGVHD)
time Frame
Up to 10 years
description
The observed rate of TRM among this subset will be calculated with 95% confidence intervals and compared descriptively to target rate.
measure
Safety of Rapid Taper of Immune Suppression for Subset of HSCT Patients With MRD >= 0.01% Pre- and/or Post-HSCT With no aGVHD Defined as < 5% Rate of Treatment-related Mortality (TRM)
time Frame
Up to 10 years
description
Blinatumomab PK will be evaluated by summarizing blinatumomab steady state concentrations and systemic clearance obtained from non-compartmental analysis. In addition, a population PK approach using a non-linear mixed effect model will also be used to assess blinatumomab PK. Exposure-response analyses will be performed to explore associations among blinatumomab exposure, relevant clinical covariates and clinical measures of safety and efficacy.
measure
Blinatumomab Pharmacokinetics (PK)
time Frame
Days 2 and 14 of cycle 1

primary Outcomes

description
DFS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). DFS is calculated as the time from randomization to date of first event (treatment failure, relapse, second malignancy, remission death) or date of last contact. Two-year DFS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
measure
Disease Free Survival (DFS) of High-risk (HR) and Intermediate-risk (IR) Relapse Patients
time Frame
Up to 2 years from date of randomization
description
DFS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). DFS is calculated as the time from randomization to date of first event (relapse, second malignancy, remission death) or date of last contact. Three-year DFS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
measure
Disease Free Survival (DFS) of Low Risk (LR) Relapse Patients
time Frame
Up to 3 years from date of randomization

secondary Outcomes

description
OS rates of HR and IR relapse B-ALL patients who are randomized following Induction Block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Two-year OS estimates will be calculated from date of randomization for both Arm A and Arm B. Two-sided 95% confidence intervals will be calculated.
measure
Overall Survival (OS) of HR and IR Relapse Patients
time Frame
Up to 2 years from date of randomization
description
OS rates of LR relapse B-ALL patients who are randomized following Block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR Randomization). OS is calculated as the time from randomization to date of death or date of last contact. Three-year OS estimates will be calculated from date of randomization for both Arm C and Arm D. Two-sided 95% confidence intervals will be calculated.
measure
Overall Survival (OS) of LR Relapse Patients
time Frame
Up to 3 years from date of randomization

Full study description

brief Summary: This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.
detailed Description: PRIMARY OBJECTIVES: I. To compare disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse B-cell acute lymphoblastic leukemia (B-ALL) patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization) as a part of a treatment regimen prior to allogeneic bone marrow transplantation. (Closed to enrollment effective September 18, 2019) II. To compare the DFS of low risk (LR) relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). (Closed to enrollment effective September 30, 2019) SECONDARY OBJECTIVES: I. To compare overall survival (OS) of HR and IR relapse B-ALL patients who are randomized following induction block 1 chemotherapy to receive either two intensive chemotherapy blocks or two 5-week blocks of blinatumomab (HR/IR randomization). (Closed to enrollment effective September 18, 2019) II. To compare OS of LR relapse B-ALL patients who are randomized following block 1 chemotherapy to receive either chemotherapy alone or chemotherapy plus blinatumomab (LR randomization). EXPLORATORY OBJECTIVES: I. To compare the rates of minimal residual disease (MRD) \>= 0.01% at the end of block 2 and block 3 for HR and IR relapse B-ALL patients in HR/IR randomization. II. To estimate, for treatment failure (TF) patients not previously receiving blinatumomab, the hematologic complete remission rate (CR), rate of MRD \< 0.01%, and proportion able to proceed to hematopoietic stem cell transplant (HSCT) in CR after treatment with blinatumomab. III. To assess the feasibility and safety of rapid taper of immune suppression for the subset of HSCT patients with MRD \>= 0.01% pre- and/or post-HSCT with no acute graft versus host disease (aGVHD). IV. To evaluate blinatumomab pharmacokinetics (PK) and explore exposure-response relationships for measures of safety and effectiveness. OUTLINE: All patients receive Block 1 over 4 weeks. BLOCK 1: Patients receive dexamethasone orally (PO) twice daily (BID) or intravenously (IV) on days 1-5 and 15-19; vincristine sulfate IV over 1 minute on days 1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 3 and 17; mitoxantrone hydrochloride IV over 15-30 minutes on days 1-2, and methotrexate intrathecally (IT) on day 1. Patients with central nervous system (CNS) 1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 (including isolated CNS relapse) also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8, 15, and 22. High risk and intermediate risk patients are then assigned to randomization R1. Low risk patients are assigned to randomization R2. RANDOMIZATION R1 (HR and IR patients): Patients are randomized to 1 of 2 treatment arms. Effective 09/18/2019, HR/IR patients not yet randomized are not eligible for post-Induction therapy on AALL1331 and will be removed from protocol therapy. Patients receiving therapy on Arm A prior to Amendment #10A who have not yet received day 22 treatment on Block 3 will be offered the opportunity to cross over to Arm B to receive blinatumomab. ARM A: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the Block 2. ARM B: Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT if eligible. Patients with persistent testicular involvement after Block 1 receive testicular radiation during the first block of blinatumomab. RANDOMIZATION R2 (LR patients): LR patients are randomized to 1 of 2 treatment arms. ARM C: Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance. CNS3 patients receive chemoradiation post-Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2. ARM D: Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance. CNS3 patients receive chemoradiation post Maintenance Cycle 1. Patients with persistent testicular involvement after Block 1 receive testicular radiation during Block 2. BLOCK 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; methotrexate IV over 36 hours on day 8; leucovorin calcium IV or PO on days 10-11; pegaspargase IV over 1-2 hours on day 9 or 10; cyclophosphamide IV over 15-30 minutes on days 15-19; and etoposide IV over 1-2 hours on days 15-19. Patients with CNS1 or CNS2 also receive methotrexate IT on day 8. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 22. BLOCK 3: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9; asparaginase intramuscularly (IM) or IV over 1 hour on days 2, 4, 9, 11, and 23; methotrexate IT on day 1and IV over 36 hours on day 22; leucovorin calcium PO or IV on days 24-25. Patients with CNS1 or CNS2 also receive methotrexate IT on day 22. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on day 22. BLINATUMOMAB BLOCK 1: Patients receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 15 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 15 and 29. BLINATUMOMAB BLOCK 2: Patients receive blinatumomab IV continuously on days 1-28. Patients with CNS1 or CNS2 also receive methotrexate IT on days 8 and 29. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 8 and 29. BLINATUMOMAB BLOCK 3: Patients receive blinatumomab IV continuously on days 1-28 and dexamethasone PO or IV on day 1. CONTINUATION 1 \& 2: Patients receive dexamethasone PO BID or IV on days 1-5; vincristine sulfate IV over 1 minute on day 1; mercaptopurine tablet PO on days 1-42; methotrexate PO on days 8, 15, 29, and 36; or; cyclophosphamide IV over 15-30 minutes on days 43 and 50; etoposide IV over 1-2 hours on days 43 and 50; thioguanine PO once daily on days 43-49; and cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 44-47 and 51-54. Patients with CNS1 or CNS2 also receive methotrexate IT on days 1 and 43, methotrexate PO every 6 hours for 4 doses on day 22, leucovorin calcium PO every 6 hours for 2 doses on day 24. Patients with CNS3 also receive methotrexate IT, hydrocortisone IT, and cytarabine IT on days 1 and 43 ; methotrexate IV over 36 hours on day 22; and leucovorin calcium IV or PO every 6 hours on days 24-25. MAINTENANCE: Patients receive dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; vincristine sulfate IV over 1 minute on days 1, 29, and 57; mercaptopurine tablet PO on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Patients with CNS1 or CNS2 also receive methotrexate IT on day 1. Patients with CNS3 receive Triple Intrathecal Therapy (ITT) on day 1. Cycles repeat every 12 weeks for up to 2 years from the beginning of treatment in the absence of disease progression or unacceptable toxicity. MAINTENANCE CHEMORADIATION (LR CNS3 PATIENTS ONLY): Following maintenance cycle 1, patients receive 1800 cGy cranial radiation; dexamethasone PO BID or IV on days 1-7 and 15-21; vincristine sulfate IV over 1 minute on days 1, 8 and 15; and pegaspargase IV over 1-2 hours on day 1. Patients then resume maintenance with cycle 2 and beyond. After completion of study treatment, patients are followed up annually for 10 years.

Source references

references

citation
Hogan LE, Bhatla T, Xu X, Gore L, Raetz EA, Bhojwani D, Teachey DT, Hunger SP, Loh ML, Brown PA, Ji L. Severe toxicity and poor efficacy of reinduction chemotherapy are associated with overall poor outcomes in relapsed B-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group AALL1331 trial. Haematologica. 2025 Dec 1;110(12):2930-2941. doi: 10.3324/haematol.2025.287386. Epub 2025 Jun 26.
pmid
40568722
type
DERIVED
citation
Hogan LE, Brown PA, Ji L, Xu X, Devidas M, Bhatla T, Borowitz MJ, Raetz EA, Carroll A, Heerema NA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Hunger SP, Loh ML. Children's Oncology Group AALL1331: Phase III Trial of Blinatumomab in Children, Adolescents, and Young Adults With Low-Risk B-Cell ALL in First Relapse. J Clin Oncol. 2023 Sep 1;41(25):4118-4129. doi: 10.1200/JCO.22.02200. Epub 2023 May 31.
pmid
37257143
type
DERIVED
citation
Brown PA, Ji L, Xu X, Devidas M, Hogan LE, Borowitz MJ, Raetz EA, Zugmaier G, Sharon E, Bernhardt MB, Terezakis SA, Gore L, Whitlock JA, Pulsipher MA, Hunger SP, Loh ML. Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. JAMA. 2021 Mar 2;325(9):833-842. doi: 10.1001/jama.2021.0669.
pmid
33651090
type
DERIVED