Clinical Trials /

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

NCT02877303

Description:

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.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Blinatumomab and Combination Chemotherapy as Frontline Therapy in Treating Patients With B Acute Lymphoblastic Leukemia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2014-0845
  • SECONDARY ID: NCI-2017-00596
  • SECONDARY ID: 2014-0845
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT02877303

Conditions

  • B Acute Lymphoblastic Leukemia
  • B Lymphoblastic Lymphoma

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Treatment (blinatumomab, combination chemotherapy)
Cyclophosphamide(-)-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- 138719Treatment (blinatumomab, combination chemotherapy)
Cytarabine.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-28453Treatment (blinatumomab, combination chemotherapy)
DexamethasoneAacidexam, 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, VisumetazoneTreatment (blinatumomab, combination chemotherapy)
Doxorubicin Hydrochloride5,12-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, RubexTreatment (blinatumomab, combination chemotherapy)
Mercaptopurine3H-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-2785Treatment (blinatumomab, combination chemotherapy)
MethotrexateAbitrexate, 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-19039Treatment (blinatumomab, combination chemotherapy)
OfatumumabArzerra, GSK1841157, HuMax-CD20, HuMax-CD20, 2F2Treatment (blinatumomab, combination chemotherapy)
Prednisone.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-PrednisoneTreatment (blinatumomab, combination chemotherapy)
RituximabABP 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, RTXM83Treatment (blinatumomab, combination chemotherapy)
Vincristine SulfateKyocristine, Leurocristine sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateTreatment (blinatumomab, combination chemotherapy)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (blinatumomab, combination chemotherapy)ExperimentalSee detailed description.
  • Blinatumomab
  • Cyclophosphamide
  • Cytarabine
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Mercaptopurine
  • Methotrexate
  • Ofatumumab
  • Prednisone
  • Rituximab
  • 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

          -  Subjects who weigh less than 45 kg
      
Maximum Eligible Age:N/A
Minimum Eligible Age:14 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Overall survival
Time Frame:Up to 24 months
Safety Issue:
Description:Will be estimated using the method of Kaplan and Meier.
Measure:Overall response rate
Time Frame:Up to 24 months
Safety Issue:
Description:Will be estimated along with the exact 95% confidence intervals.
Measure:Minimal residual disease negativity rate
Time Frame:Up to 24 months
Safety Issue:
Description:Will be estimated along with the exact 95% confidence intervals.
Measure:Incidence of adverse events
Time Frame:Up to 24 months
Safety Issue:
Description:Will be summarized by organ type, grade and attribution to study treatment.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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