Blinatumomab, Inotuzumab Ozogamicin, and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia

NCT ID: NCT02877303

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-01
• Study Completion Date: 2026-11-01

Brief Summary

This phase II trial studies how well blinatumomab, inotuzumab ozogamicin, and combination chemotherapy work as frontline therapy in treating patients with B acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone, cytarabine, mercaptopurine, methotrexate, and prednisone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving blinatumomab, inotuzumab ozogamicin, and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the clinical efficacy of the sequential combination of hyperfractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) + blinatumomab + inotuzumab ozogamicin (inotuzumab) in patients with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) in terms of relapse-free survival (RFS).

SECONDARY OBJECTIVE:

I. To evaluate other efficacy endpoints such as overall survival, overall response rate, minimal residual disease (MRD) negativity rate as well as the safety of this combination.

EXPLORATORY OBJECTIVES:

I. To identify genomic alterations in adult ALL predictive for response and long-term outcomes with the combination of hyper-CVAD plus blinatumomab and inotuzumab.

II. To evaluate the impact of next generation sequencing (NGS)-based MRD assay on outcomes and to compare with standard flow cytometry MRD assays.

OUTLINE:

INTENSIVE PHASE: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on days 1-3, dexamethasone orally (PO) once daily (QD) on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2 of cycles 1 and 3, day 8 of cycles 2 and 4, and IV over 24 hours on day 1 of cycles 2 and 4, doxorubicin hydrochloride IV continuously on day 4, vincristine sulfate IV over 15 minutes on days 4 and 11, and cytarabine IT on day 7 of cycles 1 and 3, day 5 of cycles 2 and 4, and IV over 2 hours on days 2 and 3 of cycles 2 and 4. Patients may also receive ofatumumab IV or rituximab IV over 4-6 hours on days 1 and 11 of cycles 1 and 3, and days 1 and 8 of cycles 2 and 4 at the discretion of the treating physician. Patients may receive ofatumumab IV over 4-6 hours on day 2 of cycle 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

BLINATUMOMAB AND INOTUZUMAB OZOGAMICIN PHASE (CYCLES 5-8): Patients receive blinatumomab IV continuously on weeks 1-4. Patients also receive inotuzumab ozogamicin IV over 1 hour on days 5 and 11 of cycles 6 and 8. Treatment repeats every 6 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE PHASE: At doctor's discretion, patients may receive maintenance therapy prior to completing 4 cycles of hyper-CVAD and/or 4 cycles of blinatumomab. Patients receive mercaptopurine PO thrice daily (TID), methotrexate PO every week, vincristine sulfate IV over 15 minutes every month, and prednisone PO on days 1-5. Cycles repeat every 6 weeks for 12 months in the absence of disease progression or unacceptable toxicity. Patients also receive blinatumomab IV after every 3 cycles of maintenance therapy for a total of about 15 cycles.

After completion of study treatment, patients are followed up 1 time each month for up to 24 months.

Conditions

B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (blinatumomab, inotuzumab, combination chemotherapy)

See detailed description.

Group Type: EXPERIMENTAL

Blinatumomab

Intervention Type: BIOLOGICAL

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT and IV

Dexamethasone

Intervention Type: DRUG

Given PO

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Inotuzumab Ozogamicin

Intervention Type: BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT, IV, and PO

Ofatumumab

Intervention Type: BIOLOGICAL

Given IV

Prednisone

Intervention Type: DRUG

Given PO

Rituximab

Intervention Type: BIOLOGICAL

Given IV

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Interventions

Blinatumomab

Given IV

Intervention Type: BIOLOGICAL

Cyclophosphamide

Given IV

Intervention Type: DRUG

Cytarabine

Given IT and IV

Intervention Type: DRUG

Dexamethasone

Given PO

Intervention Type: DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Inotuzumab Ozogamicin

Given IV

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Mercaptopurine

Given PO

Intervention Type: DRUG

Methotrexate

Given IT, IV, and PO

Intervention Type: DRUG

Ofatumumab

Given IV

Intervention Type: BIOLOGICAL

Prednisone

Given PO

Intervention Type: DRUG

Rituximab

Given IV

Intervention Type: BIOLOGICAL

Vincristine Sulfate

Given IV

Intervention Type: DRUG

Other Intervention Names

Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody; Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103; Blincyto; MEDI-538; MT-103; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Carloxan; Ciclofosfamida; Ciclofosfamide; Cicloxal; Clafen; Claphene; CP monohydrate; CTX; CYCLO-cell; Cycloblastin; Cycloblastine; Cyclophospham; Cyclophosphamid monohydrate; Cyclophosphamide Monohydrate; Cyclophosphamidum; Cyclophosphan; Cyclophosphane; Cyclophosphanum; Cyclostin; Cyclostine; Cytophosphan; Cytophosphane; Cytoxan; Fosfaseron; Genoxal; Genuxal; Ledoxina; Mitoxan; Neosar; Revimmune; Syklofosfamid; WR- 138719; .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; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Aacidexam; Adexone; Aknichthol Dexa; Alba-Dex; Alin; Alin Depot; Alin Oftalmico; Amplidermis; Anemul mono; Auricularum; Auxiloson; Baycadron; Baycuten; Baycuten N; Cortidexason; Cortisumman; Decacort; Decadrol; Decadron; Decadron DP; Decalix; Decameth; Decasone R.p.; Dectancyl; Dekacort; Deltafluorene; Deronil; Desamethasone; Desameton; Dexa-Mamallet; Dexa-Rhinosan; Dexa-Scheroson; Dexa-sine; Dexacortal; Dexacortin; Dexafarma; Dexafluorene; Dexalocal; Dexamecortin; Dexameth; Dexamethasone Intensol; Dexamethasonum; Dexamonozon; Dexapos; Dexinoral; Dexone; Dinormon; Fluorodelta; Fortecortin; Gammacorten; Hexadecadrol; Hexadrol; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI); ADM; Adriacin; Adriamycin; Adriamycin Hydrochloride; Adriamycin PFS; Adriamycin RDF; ADRIAMYCIN, HYDROCHLORIDE; Adriamycine; Adriblastina; Adriblastine; Adrimedac; Chloridrato de Doxorrubicina; DOX; DOXO-CELL; Doxolem; Doxorubicin HCl; Doxorubicin.HCl; Doxorubin; Farmiblastina; FI 106; FI-106; hydroxydaunorubicin; Rubex; Besponsa; CMC-544; Way 207294; WAY-207294; 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; Alti-Mercaptopurine; Azathiopurine; Bw 57-323H; Flocofil; Ismipur; Leukerin; Leupurin; Mercaleukim; Mercaleukin; Mercaptina; Mercaptopurinum; Mercapurin; Mern; NCI-C04886; Puri-Nethol; Purimethol; Purine, 6-mercapto-; Purine-6-thiol (8CI); Purine-6-thiol, monohydrate; Purinethiol; Purinethol; U-4748; WR-2785; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Arzerra; GSK1841157; HuMax-CD20; HuMax-CD20, 2F2; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; ABP 798; BI 695500; C2B8 Monoclonal Antibody; Chimeric Anti-CD20 Antibody; CT-P10; IDEC-102; IDEC-C2B8; IDEC-C2B8 Monoclonal Antibody; MabThera; Monoclonal Antibody IDEC-C2B8; PF-05280586; Rituxan; Rituximab ABBS; Rituximab Biosimilar ABP 798; Rituximab Biosimilar BI 695500; Rituximab Biosimilar CT-P10; Rituximab Biosimilar GB241; Rituximab Biosimilar IBI301; Rituximab Biosimilar JHL1101; Rituximab Biosimilar PF-05280586; Rituximab Biosimilar RTXM83; Rituximab Biosimilar SAIT101; rituximab biosimilar TQB2303; rituximab-abbs; RTXM83; Truxima; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate

Eligibility Criteria

Inclusion Criteria

• Patients with newly diagnosed, previously untreated B-lineage ALL or lymphoblastic lymphoma, or having achieved complete remission (CR) with one course of induction chemotherapy; patients who require steroids, cytarabine (ara-c) or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
• Failure to one induction course of chemotherapy (these patients will be analyzed separately); patients who require steroids, ara-c or hydrea to manage disease symptoms prior to finalization of diagnosis and treatment plan are allowed and eligible
• Performance status of 0-3
• Creatinine less than or equal to 2.0 mg/dL (unless considered tumor related)
• Bilirubin less than or equal to 2.0 mg/dL (unless considered tumor related)
• Adequate cardiac function as assessed by history and physical examination
• No active or co-existing malignancy with life expectancy less than 12 months, sources for the determination of clinical significance by the treating physician will be included in the subject's medical record

Exclusion Criteria

• Pregnant or nursing women
• Known to be human immunodeficiency virus (HIV)-positive
• Philadelphia chromosome (Ph)-positive ALL
• Active and uncontrolled disease/infection as judged by the treating physician, sources for the determination of clinical significance by the treating physician will be included in the subject's medical record
• Unable or unwilling to sign the consent form
• Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per treating physician assessment), sources for the determination of clinical significance by the treating physician will be included in the subject's medical record
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; (Patients with CNS involvement of leukemia are NOT excluded)
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement; auto-immune disease with possible CNS consequences/manifestations such as such as epilepsy, paresis, aphasia, stroke, dementia, Parkinson's disease, cerebellar disease, or psychosis

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elias Jabbour

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Elias Jabbour

Role: CONTACT

ejabbour@mdanderson.org

713-792-4764

Facility Contacts

Elias Jabbour

Role: primary

ejabbour@mdanderson.org

713-792-4764

References

Jabbour E, Short NJ, Jain N, Thompson PA, Kadia TM, Ferrajoli A, Huang X, Yilmaz M, Alvarado Y, Patel KP, Garcia-Manero G, Macaron W, Garris R, Konopleva M, Ravandi F, Kantarjian H. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022 Dec;9(12):e878-e885. doi: 10.1016/S2352-3026(22)00285-X. Epub 2022 Oct 22.

Reference Type: DERIVED

PMID: 36279879 (View on PubMed)

Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

Reference Type: DERIVED

PMID: 35622074 (View on PubMed)

Jabbour E, Kantarjian H. The Hyper-CVAD Regimen is an Optimal Pediatric-inspired Regimen for Adolescents and Adults With Acute Lymphoblastic Leukemia. Clin Lymphoma Myeloma Leuk. 2021 Jan;21(1):63-65. doi: 10.1016/j.clml.2020.09.001. Epub 2020 Oct 24. No abstract available.

Reference Type: DERIVED

PMID: 33191168 (View on PubMed)

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

NCI-2017-00596

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-0845

Identifier Type: OTHER

Identifier Source: secondary_id

2014-0845

Identifier Type: -

Identifier Source: org_study_id