Clinical Trial: NCT02101853 - My Cancer Genome

NCT02101853

Description:

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 induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether standard combination chemotherapy is more effective than blinatumomab in treating relapsed B-cell acute lymphoblastic leukemia.

Related Conditions:

B-Cell Acute Lymphoblastic Leukemia

Recruiting Status:

Active, not recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT02101853

Trial Eligibility

Document

Title

Brief Title: Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Official Title: Risk-Stratified Randomized Phase III Testing of Blinatumomab (NSC#765986) in First Relapse of Childhood B-Lymphoblastic Leukemia (B-ALL)

Clinical Trial IDs

ORG STUDY ID: NCI-2014-00631
SECONDARY ID: NCI-2014-00631
SECONDARY ID: s15-00970
SECONDARY ID: COG-AALL1331
SECONDARY ID: AALL1331
SECONDARY ID: AALL1331
SECONDARY ID: U10CA180886
SECONDARY ID: U10CA098543
NCT ID: NCT02101853

Conditions

Recurrent B Acute Lymphoblastic Leukemia

Interventions

Drug	Synonyms	Arms
Asparaginase	ASP-1, Asparaginase II, Asparaginase-E.Coli, Colaspase, Elspar, Kidrolase, L-Asnase, L-ASP, L-Asparaginase, L-Asparagine Amidohydrolase, Laspar, Lcf-ASP, Leucogen, Leunase, MK-965, Paronal, Re-82-TAD-15, Serasa, Spectrila	Arm A (HR and IR control)
Blinatumomab	Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103	Arm B (HR and IR blinatumomab)
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, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719	Arm A (HR and IR control)
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-28453	Arm A (HR and IR control)
Dexamethasone	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, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex	Arm A (HR and IR control)
Etoposide	Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16	Arm A (HR and IR control)
Leucovorin Calcium	Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin	Arm A (HR and IR control)
Mercaptopurine	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	Arm C (LR control)
Methotrexate	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	Arm A (HR and IR control)
Mitoxantrone	Dihydroxyanthracenedione, Mitozantrone	Arm A (HR and IR control)
Mitoxantrone Hydrochloride	CL 232315, DHAD, DHAQ, Dihydroxyanthracenedione Dihydrochloride, Mitoxantrone Dihydrochloride, Mitoxantroni Hydrochloridum, Mitozantrone Hydrochloride, Mitroxone, Neotalem, Novantrone, Onkotrone, Pralifan	Arm A (HR and IR control)
Pegaspargase	L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase, PEG-L-Asparaginase, PEG-L-Asparaginase (Enzon - Kyowa Hakko), PEGLA, Polyethylene Glycol L-Asparaginase, Polyethylene Glycol-L-Asparaginase	Arm A (HR and IR control)
Therapeutic Hydrocortisone	Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, Hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid	Arm A (HR and IR control)
Thioguanine	2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol, 2-Aminopurin-6-thiol, 2-Aminopurine-6(1H)-thione, 2-Aminopurine-6-thiol, 2-Aminopurine-6-thiol Hemihydrate, 2-Mercapto-6-aminopurine, 6-Amino-2-mercaptopurine, 6-Mercapto-2-aminopurine, 6-Mercaptoguanine, 6-TG, 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI), BW 5071, Lanvis, Tabloid, Thioguanine Hemihydrate, Thioguanine Hydrate, Tioguanin, Tioguanine, Wellcome U3B, WR-1141, X 27	Arm C (LR control)
Vincristine	Leurocristine, VCR, Vincrystine	Arm A (HR and IR control)
Vincristine Sulfate	Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate	Arm A (HR and IR control)

Purpose

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). (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).

      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 or
      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): Patients are then 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 also receive
      methotrexate IT, hydrocortisone IT, and cytarabine IT on day 1. Cycles repeat every 12 weeks
      for up to 2 years since 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.

Trial Arms

Name	Type	Description	Interventions
Arm A (HR and IR control)	Active Comparator	Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.	Asparaginase Cyclophosphamide Cytarabine Dexamethasone Etoposide Leucovorin Calcium Methotrexate Mitoxantrone Mitoxantrone Hydrochloride Pegaspargase Therapeutic Hydrocortisone Vincristine Vincristine Sulfate
Arm B (HR and IR blinatumomab)	Experimental	Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.	Blinatumomab Cytarabine Dexamethasone Methotrexate Therapeutic Hydrocortisone
Arm C (LR control)	Active Comparator	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.	Asparaginase Cyclophosphamide Cytarabine Dexamethasone Etoposide Leucovorin Calcium Mercaptopurine Methotrexate Pegaspargase Therapeutic Hydrocortisone Thioguanine Vincristine Vincristine Sulfate
Arm D (LR blinatumomab)	Experimental	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.	Blinatumomab Cyclophosphamide Cytarabine Dexamethasone Etoposide Leucovorin Calcium Mercaptopurine Methotrexate Pegaspargase Therapeutic Hydrocortisone Thioguanine Vincristine Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  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)

Maximum Eligible Age:	30 Years
Minimum Eligible Age:	1 Year
Eligible Gender:	All
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Disease free survival (DFS) of high-risk (HR) and intermediate-risk (IR) relapse patients
Time Frame:	From randomization to first event (treatment failure, relapse, second malignancy, death) or last follow-up for those who are event-free, assessed up to 10 years
Safety Issue:
Description:	Comparison of DFS rates between treatment arms will be based on log rank test. Interim analysis will be conducted to monitor for efficacy and futility. The efficacy stopping boundaries are based on the O' Brien-Fleming spending function. The futility boundaries are based on testing the alternative hypothesis at the 0.024 level.

Secondary Outcome Measures

Measure:	Overall survival (OS) of HR and IR relapse patients
Time Frame:	From randomization to death or last follow-up, assessed up to 10 years
Safety Issue:
Description:	Comparison of OS rates between treatment arms will be based on log rank test.

Measure:	OS of lLR relapse patients
Time Frame:	From randomization to death or last follow-up, assessed up to 10 years
Safety Issue:
Description:	Comparison of OS rates between treatment arms will be based on log rank test.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Active, not recruiting
Lead Sponsor:	National Cancer Institute (NCI)

Last Updated

August 25, 2021

Clinical Trials /

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