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

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ClinicalTrials.gov Identifier: NCT02877303
Recruitment Status : Recruiting
First Posted : August 24, 2016
Last Update Posted : May 16, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
This phase II trial studies how well blinatumomab 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. 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 and combination chemotherapy may work better in treating patients with B acute lymphoblastic leukemia than chemotherapy alone.

Condition or disease Intervention/treatment Phase
B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Biological: Blinatumomab Drug: Cyclophosphamide Drug: Cytarabine Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis Drug: Mercaptopurine Drug: Methotrexate Biological: Ofatumumab Drug: Prednisone Biological: Rituximab Drug: Vincristine Sulfate Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

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.

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 course 1. Treatment repeats every 3 weeks for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

BLINATUMOMAB PHASE: Patients receive blinatumomab IV continuously on weeks 1-4. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of the Hyper-CVAD Regimen in Sequential Combination With Blinatumomab as Frontline Therapy for Adults With B-Cell Lineage Acute Lymphocytic Leukemia
Actual Study Start Date : November 1, 2016
Estimated Primary Completion Date : November 1, 2020
Estimated Study Completion Date : November 1, 2020


Arm Intervention/treatment
Experimental: Treatment (blinatumomab, combination chemotherapy)
See detailed description.
Biological: Blinatumomab
Given IV
Other Names:
  • Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody
  • Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103
  • Blincyto
  • MEDI-538
  • MT-103

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719

Drug: Cytarabine
Given IT and IV
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
  • 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

Drug: Dexamethasone
Given PO
Other Names:
  • Aacidexam
  • Adexone
  • Aknichthol Dexa
  • Alba-Dex
  • Alin
  • Alin Depot
  • Alin Oftalmico
  • Amplidermis
  • Anemul mono
  • Auricularum
  • Auxiloson
  • Baycuten
  • Baycuten N
  • Cortidexason
  • Cortisumman
  • Decacort
  • Decadrol
  • Decadron
  • 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
  • Dexamethasonum
  • Dexamonozon
  • Dexapos
  • Dexinoral
  • Dexone
  • Dinormon
  • Fluorodelta
  • Fortecortin
  • Gammacorten
  • Hexadecadrol
  • Hexadrol
  • Lokalison-F
  • Loverine
  • Methylfluorprednisolone
  • Millicorten
  • Mymethasone
  • Orgadrone
  • Spersadex
  • Visumetazone

Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
  • 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
  • Doxorubin
  • Farmiblastina
  • FI 106
  • FI-106
  • hydroxydaunorubicin
  • Rubex

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Mercaptopurine
Given PO
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
  • 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

Drug: Methotrexate
Given IT, IV, and PO
Other Names:
  • 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

Biological: Ofatumumab
Given IV
Other Names:
  • Arzerra
  • GSK1841157
  • HuMax-CD20
  • HuMax-CD20, 2F2

Drug: Prednisone
Given PO
Other Names:
  • .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
  • PRED
  • Predicor
  • Predicorten
  • Prednicen-M
  • Prednicort
  • Prednidib
  • Prednilonga
  • Predniment
  • Prednisonum
  • Prednitone
  • Promifen
  • Servisone
  • SK-Prednisone

Biological: Rituximab
Given IV
Other Names:
  • 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 Biosimilar ABP 798
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar CT-P10
  • Rituximab Biosimilar GB241
  • Rituximab Biosimilar IBI301
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • Rituximab Biosimilar SAIT101
  • RTXM83

Drug: Vincristine Sulfate
Given IV
Other Names:
  • Kyocristine
  • Leurocristine sulfate
  • Leurocristine, sulfate
  • Oncovin
  • Vincasar
  • Vincosid
  • Vincrex
  • Vincristine, sulfate




Primary Outcome Measures :
  1. Relapse-free survival (RFS) [ Time Frame: From date of treatment start until the date of death or disease relapse, assessed for up to 24 months ]
    Will be estimated using the method of Kaplan and Meier. Will compute the Bayesian posterior probability. Will perform a competing risk analysis treating stem cell transplant as a competing event for RFS.


Secondary Outcome Measures :
  1. Overall survival [ Time Frame: Up to 24 months ]
    Will be estimated using the method of Kaplan and Meier.

  2. Overall response rate [ Time Frame: Up to 24 months ]
    Will be estimated along with the exact 95% confidence intervals.

  3. Minimal residual disease negativity rate [ Time Frame: Up to 24 months ]
    Will be estimated along with the exact 95% confidence intervals.

  4. Incidence of adverse events [ Time Frame: Up to 24 months ]
    Will be summarized by organ type, grade and attribution to study treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   14 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • Subjects who weigh less than 45 kg

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02877303


Contacts
Layout table for location contacts
Contact: Elias Jabbour 713-792-4764 ejabbour@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Elias Jabbour    713-792-4764      
Principal Investigator: Elias Jabbour         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Elias Jabbour M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02877303     History of Changes
Other Study ID Numbers: 2014-0845
NCI-2017-00596 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0845 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 24, 2016    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Prednisone
Cortisone
Dexamethasone acetate
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Methotrexate
Vincristine
Ofatumumab
Mercaptopurine
Blinatumomab
Antineoplastic Agents, Immunological
Muromonab-CD3
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Antibodies, Bispecific
Visilizumab