Clinical Trials /

Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

NCT04530565

Description:

This phase III trial compares the effect of usual treatment of chemotherapy and steroids and a tyrosine kinase inhibitor (TKI) to the same treatment plus blinatumomab. Blinatumomab is a Bi-specific T-Cell Engager ('BiTE') that may interfere with the ability of cancer cells to grow and spread. The information gained from this study may help researchers determine if combination therapy with steroids, TKIs, and blinatumomab work better than the standard of care.

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

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Testing the Use of Steroids and Tyrosine Kinase Inhibitors With Blinatumomab or Chemotherapy for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults
  • Official Title: A Phase III Randomized Trial of Steroids+Tyrosine Kinase Inhibitor Induction With Chemotherapy or Blinatumomab for Newly Diagnosed BCR-ABL-Positive Acute Lymphoblastic Leukemia in Adults

Clinical Trial IDs

  • ORG STUDY ID: NCI-2020-06381
  • SECONDARY ID: NCI-2020-06381
  • SECONDARY ID: EA9181
  • SECONDARY ID: EA9181
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT04530565

Conditions

  • B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1

Interventions

DrugSynonymsArms
BlinatumomabAnti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI-538, MT-103Arm C (steroid, TKI, chemotherapy, immunotherapy)
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- 138719Arm B (steroid, TKI, 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-28453Arm B (steroid, TKI, chemotherapy)
DasatinibBMS-354825, Dasatinib Hydrate, Dasatinib Monohydrate, SprycelArm A (steroid, TKI)
DexamethasoneAacidexam, 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, ZoDexArm B (steroid, TKI, 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, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexArm B (steroid, TKI, 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-19039Arm B (steroid, TKI, chemotherapy)
Ponatinib HydrochlorideAP24534 HCl, IclusigArm A (steroid, TKI)
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, Perrigo Prednisone, PRED, Predicor, Predicorten, Prednicen-M, Prednicort, Prednidib, Prednilonga, Predniment, Prednisone Intensol, Prednisonum, Prednitone, Promifen, Rayos, Servisone, SK-PrednisoneArm A (steroid, TKI)
Vincristine SulfateKyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateArm B (steroid, TKI, chemotherapy)

Purpose

This phase III trial compares the effect of the combination of steroids, potent tyrosine kinase inhibitors (TKI), and blinatumomab versus treatment with steroids, TKI, and chemotherapy. The usual approach for the treatment of acute lymphoblastic leukemia (ALL) is chemotherapy, monoclonal antibodies, or targeted therapies that kill leukemia cells. These treatments are effective and typically control the ALL for a number of years, but are not curative and usually require chronic, indefinite treatment. Anti-inflammatory drugs, such as dexamethasone and prednisone lower the body's immune response and are used with other drugs in the treatment of some types of cancer. Methotrexate may slow the growth of cancer cells. Ponatinib and dasatinib and may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as cyclophosphamide, doxorubicin, vincristine, and cytarabine 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. The information gained from this study may help researchers to compare overall survival following the study approach with steroids, TKI, and blinatumomab versus the usual approach.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To compare the overall survival (OS) following induction with steroids + TKI +
      blinatumomab versus induction with steroids + TKI + chemotherapy.

      SECONDARY OBJECTIVES:

      I. To compare the rate of minimal residual disease (MRD) negativity for patients treated with
      chemotherapy versus (vs) blinatumomab at the end of first induction (week 15).

      II. To evaluate the rate of the MRD negativity by treatment arm for those patients MRD
      positive after the first induction and administered of second induction.

      III. To compare event free survival (EFS) for patients initially randomized for chemotherapy
      vs blinatumomab.

      IV. To assess the toxicities of blinatumomab + TKI and steroids + TKI + chemotherapy in this
      patient population.

      V. To assess the toxicities of the chemotherapy regimen in this patient population.

      VI. To describe the outcome of patients who proceed to allogeneic stem cell transplant after
      treatment with blinatumomab + TKI only.

      OUTLINE:

      ARM A (RUN-IN): Patients receive prednisone orally (PO) once daily (QD) on days 1-21 and
      ponatinib hydrochloride (ponatinib) PO QD or dasatinib PO QD on days 1-21 based on
      investigator's choice.

      Patients are randomized to 1 of 2 arms (Arm B or C).

      ARM B (INDUCTION THERAPY):

      CYCLE 1: Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO
      QD on days 1-21. Patients also receive cyclophosphamide intravenously (IV) twice daily (BID)
      on days 1-3, dexamethasone PO or IV on days 1-4 and 11-14, cytarabine intrathecally (IT) on
      day 1, doxorubicin hydrochloride (doxorubicin) IV on day 4, vincristine sulfate (vincristine)
      IV on days 4 and 11, and methotrexate IT on day 8.

      CYCLE 2 (AGE 18-70): Starting in cycle 2, fit patients aged 18-70 receive prednisone PO QD on
      days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21. Patients also receive
      methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours on days 2-3. On
      day 22 of cycle 2 or later, as soon as the absolute neutrophil count (ANC) is greater than
      1000 cells/ul and platelets are greater than 50,000 cells/ul, patients receive hyper
      cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) for 2 additional cycles.

      CYCLE 2 (AGE > 70): Starting in cycle 2, patients age > 70 or younger unfit patients receive
      prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21. Patients
      also receive methotrexate IV over 24 hours and IT on day 1, and cytarabine IV over 2 hours on
      days 2-3. Cycle 1 and 2 regimens are each repeated once starting on day 22 of cycle 2, or
      later, but as soon as the ANC is greater than 1000 cells/ul and platelets are greater than
      50,000 cells/ul.

      Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or
      unacceptable toxicity. Patients who achieve remission (significant reduction in the amount of
      leukemia in bone marrow and blood/MRD negative) after 4 cycles may receive alternative
      treatment, either TKI maintenance therapy or undergo allogeneic stem cell transplantation.
      Patients who do not achieve a remission (MRD positive) are assigned to Arm D. Patients who
      experience un-resolving renal failure or life-threatening infection which may require a delay
      of 21 days cross-over to Arm C to receive the prescribed course of blinatumomab.

      ARM C (INDUCTION THERAPY):

      CYCLE 1: Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO
      QD on days 1-21. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV
      continuously on days 1-28, followed by methotrexate IT on day 28 or 29.

      CYCLE 2: Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO
      QD on days 1-21. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV
      continuously on days 1-28.

      Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or
      unacceptable toxicity.

      ARM D (RE-INDUCTION): Patients treated on Arm B who remain MRD positive at the end of
      induction therapy receive blinatumomab based re-induction identical to the regimen described
      for Arm C.

      ARM E (RE-INDUCTION): Patients treated on Arm C who remain MRD positive at the end of
      induction therapy receive chemotherapy based re-induction which is identical to regimen
      described for Arm B according to patient's age and the pre-specified chemotherapy arm.

      Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at
      the discretion of the investigator, or receive anti CD-19 CAR- T cell therapy, inotuzumab
      ozogamicin, intensive chemotherapy, or palliative care.

      Patients are followed up for 10 years from the date of registration.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (steroid, TKI)Active ComparatorPatients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21 based on investigator's choice.
  • Dasatinib
  • Ponatinib Hydrochloride
  • Prednisone
Arm B (steroid, TKI, chemotherapy)ExperimentalSee Detailed Description.
  • Cyclophosphamide
  • Cytarabine
  • Dasatinib
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Methotrexate
  • Ponatinib Hydrochloride
  • Prednisone
  • Vincristine Sulfate
Arm C (steroid, TKI, chemotherapy, immunotherapy)ExperimentalCYCLE 1: Patients receive prednisone PO QD on days 1-21, and ponatinib PO QD or dasatinib PO QD on days 1-21. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28, followed by methotrexate IT on day 28 or 29. CYCLE 2: Patients receive prednisone PO QD on days 1-21 and ponatinib PO QD or dasatinib PO QD on days 1-21. Patients also receive dexamethasone PO or IV on day 1 and blinatumomab IV continuously on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
  • Blinatumomab
  • Dasatinib
  • Dexamethasone
  • Methotrexate
  • Ponatinib Hydrochloride
  • Prednisone
Arm D (steroid, TKI, chemotherapy, immunotherapy)ExperimentalPatients treated on Arm B who remain MRD positive at the end of induction therapy receive blinatumomab based re-induction identical to the regimen described for Arm C. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator, or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.
  • Blinatumomab
  • Cyclophosphamide
  • Dasatinib
  • Dexamethasone
  • Methotrexate
  • Ponatinib Hydrochloride
  • Prednisone
Arm E (steroid, TKI, chemotherapy)ExperimentalPatients treated on Arm C who remain MRD positive at the end of induction therapy receive chemotherapy based re-induction which is identical to regimen described for Arm B according to patient's age and the pre-specified chemotherapy arm. Patients whose molecular test remains MRD positive after re-induction proceed to follow-up at the discretion of the investigator, or receive anti CD-19 CAR- T cell therapy, inotuzumab ozogamicin, intensive chemotherapy, or palliative care.
  • Cyclophosphamide
  • Cytarabine
  • Dasatinib
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Methotrexate
  • Ponatinib Hydrochloride
  • Prednisone
  • Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - INCLUSION

          -  Patient must be newly diagnosed with B-ALL or is suspected to have ALL

               -  Patient must have BCR-ABL1 positive disease. The diagnosis of ALL and the
                  presence of BCR-ABL translocation must be confirmed centrally. Patients can be
                  registered and begin Step 1 therapy while awaiting central laboratory eligibility
                  confirmation

                    -  NOTE: Bone marrow and/or peripheral blood specimen must be submitted to the
                       Eastern Cooperative Oncology Group-American College of Radiology Imaging
                       Network (ECOG-ACRIN) Leukemia Laboratory at MD Anderson Cancer Center to
                       determine patient's eligibility for registration to Step 1 or confirm
                       patient evaluability. Centrally fluorescence-activated cell sorting (FACS)
                       analysis will be performed to determine B-ALL and to exclude acute myeloid
                       leukemia (AML) or acute bi-phenotypic leukemia and baseline BCR-ABL status
                       will be determined by fluorescent in situ hybridization (FISH). The
                       ECOG-ACRIN Leukemia Laboratory will forward results within 48 hours of
                       receipt of the specimen to the submitting institution. Bone marrow is to be
                       from first pull (initial or re-direct). Specimens must contain sufficient
                       blast cells. In cases where the bone marrow aspiration may be inadequate, or
                       the bone marrow examination has already been performed prior to study
                       consent and enrollment on Step 0, peripheral blood may be submitted, given
                       that adequate circulating blasts are present (> 10%). If a diagnosis of
                       BCR-ABL positive B-ALL has already been established by local Clinical
                       Laboratory Improvement Act (CLIA) certified laboratories, the patient may be
                       registered to Step 1 without waiting for central confirmation

          -  Patients who started any kind of TKI prior to study registration are allowed to
             proceed on the study if they received no more than 14 days of TKI

          -  STEP 1 REGISTRATION ELIGIBILITY CRITERIA - INCLUSION

          -  The diagnosis of Philadelphia chromosome positive (Ph+) ALL has been determined
             locally, and bone marrow and/or peripheral blood was sent for central confirmation or
             determined centrally by the ECOG-ACRIN Leukemia Laboratory at MD Anderson Cancer
             Center

          -  Women of childbearing potential and sexually active males must not expect to conceive
             or father children by using accepted and effective method(s) of contraception or by
             abstaining from sexual intercourse from the time of registration, while on study
             treatment, and until at least six months after the last dose of study treatment

          -  Total bilirubin =< 3 mg/dL (unless related to Gilbert's syndrome in which case total
             bilirubin must be =< 5 mg/dL)

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 X the institutional upper limit of normal (ULN)

          -  Estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation)

          -  Patients with acute organ dysfunction at registration, which may be attributed to
             leukemia can be registered regardless of lab results at presentation. Such patients
             will be allowed to register and can start Arm A steroid + TKI therapy but will only be
             allowed to proceed to Step 2 randomization if the eligibility criteria outlined is met

          -  Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
             therapy with undetectable viral load within 6 months are eligible for this trial

          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral
             load must be undetectable or on suppressive therapy, if indicated

          -  Patients with a history of hepatitis C virus (HCV) infection must have an undetectable
             HCV viral load and if indicated, on treatment

          -  Patients with a prior malignancy whose natural history or treatment does not have the
             potential to interfere with the safety or efficacy assessment of the investigational
             regimen are eligible for this trial

          -  Patients with known history or current symptoms of cardiac disease, or history of
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
             function using the New York Heart Association Functional Classification. To be
             eligible for this trial, patients must be class 2B or better

          -  Investigators must confirm which TKI patient is to receive

               -  NOTE: Patients with known T315I mutation status should receive ponatinib
                  treatment

               -  NOTE: In situations due to insurance coverage issues and the pre-selected TKI is
                  not immediately available, patients can receive dasatinib or imatinib during Step
                  1. The investigator must re-specify dasatinib or ponatinib prior to Step 2
                  randomization and from then on patients must receive the pre-selected TKI only

          -  STEP 2: RANDOMIZATION - ELIGIBILITY CRITERIA - INCLUSION

          -  Patient must have completed at least 7 of 21 days of protocol-treatment on Arm A prior
             to randomization

               -  NOTE: First day of steroids prescription after registration will be considered as
                  the first day of study therapy. The selected TKI should be initiated prior to
                  randomization

          -  Patients who presented with acute organ dysfunction at Step 1 must have their total
             bilirubin and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN and have an
             estimated creatinine clearance > 45 mg/min (based on Cockcroft-Gault equation)

          -  Investigators must confirm which TKI patient is to receive.

               -  NOTE: Patients with known T315I mutation status should receive ponatinib
                  treatment

          -  For patients under age 70, intended chemotherapy regimen must have been determined
             prior to randomization

          -  STEP 3: REGISTRATION (RE-INDUCTION) - ELIGIBILITY CRITERIA - INCLUSION

          -  Institution has received centralized MRD results confirming positive status

          -  Patients who presented with acute organ dysfunction must have their total bilirubin
             and AST (SGOT)/ALT (SGPT) reduce to < 2 X institutional ULN

          -  Patients who presented with acute organ dysfunction must have an estimated creatinine
             clearance > 45 mg/min (based on Cockcroft-Gault equation)

          -  Investigators must confirm which TKI patient is to receive

               -  NOTE: Patients with known T315I mutation status should receive ponatinib
                  treatment

          -  For patients under age 70 and previously assigned to Arm C, intended chemotherapy
             regimen must have been determined

        Exclusion Criteria:

          -  PREREGISTRATION (STEP 0) ELIGIBILITY CRITERIA - EXCLUSION

          -  Patient must not have received chemotherapy for B-ALL. Patients who received up to
             five days of hydroxyurea or steroids of any kind with the aim to reduce disease burden
             prior to study registration are eligible

          -  Patient must not have unstable epilepsy that requires treatment

          -  STEP 1 REGISTRATION ELIGIBILITY CRITERIA - EXCLUSION

          -  Women must not be pregnant or breast-feeding due to the potential harm to an unborn
             fetus and possible risk for adverse events in nursing infants with the treatment
             regimens being used. All females of childbearing potential must have a blood test or
             urine study within 14 days prior to registration to rule out pregnancy. A female of
             childbearing potential is defined as any woman, regardless of sexual orientation or
             whether they have undergone tubal ligation, who meets the following criteria: 1) has
             achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral
             oophorectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer
             therapy does not rule out childbearing potential) for at least 24 consecutive months
             (i.e., has had menses at any time in the preceding 24 consecutive months)

          -  Patient must not have active concomitant malignancy. Patients on chronic hormonal
             therapy for breast or prostate cancer or patients treated with maintenance with
             targeted agents but are in remission with no evidence for the primary malignancies can
             be included

          -  Patients must not have complaints of symptoms and/or have clinical and/or radiological
             signs that indicate an uncontrolled infection or any other concurrent medical
             condition that could be exacerbated by the treatment or would seriously complicate
             compliance with the protocol

          -  STEP 2: RANDOMIZATION - ELIGIBILITY CRITERIA - EXCLUSION

          -  Patient must not have active central nervous system (CNS) involvement by leukemic
             blasts. Patients with signs of CNS involvement at presentation are eligible for
             randomization if clearance of blasts from the cerebrospinal fluid (CSF) is
             demonstrated
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Time between randomization and death from any cause, assessed up to 10 years from the date of registration
Safety Issue:
Description:Will compare OS following induction with steroids + tyrosine kinase inhibitor (TKI) + blinatumomab and induction with steroids + TKI + chemotherapy. Will be based on an intent-to-treat analysis. Estimates of OS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of OS between treatment arms will be conducted using the one-sided stratified log-rank test with steroid responsiveness, type of TKI intended to receive and age at diagnosis, the same factors used in randomization, as stratification factors. Cox proportional hazards models of OS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities.

Secondary Outcome Measures

Measure:Rate of minimal residual disease (MRD) negativity
Time Frame:At week 15
Safety Issue:
Description:Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negativity and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measure:Event free survival (EFS)
Time Frame:Time from randomization to failure to achieve induction molecular remission by week 15, confirmed molecular relapse after molecular remission or to death in remission, assessed up to 10 years from the date of registration
Safety Issue:
Description:Will be based on an intent-to-treat analysis. Estimates of EFS including medians and confidence intervals, will be calculated using the Kaplan-Meier method. Comparisons of EFS between treatment arms will be conducted using the one-sided stratified log-rank test with steroid responsiveness, type of TKI intended to receive and age at diagnosis, the same factors used in randomization, as stratification factors. Cox proportional hazards models of EFS, stratified on the same factors used in the randomization, will be used to assess the effect of treatment by adjusting other possible clinical and biological risk factors, including cytogenetic abnormalities
Measure:Rate of MRD negativity
Time Frame:After re-induction and safety
Safety Issue:
Description:Will be centrally evaluated. Will be compared between two arms using Fisher's exact test with a one-sided type I error rate of 2.5%. Multivariable logistic regression modeling will be used to adjust for other possible clinical and biological risk factors. For patients registered to Step 3 (re-induction), the rates of MRD negativity and their corresponding 95% confidence intervals after re-induction will be given by treatment arm.
Measure:Incidence of adverse events
Time Frame:Up to 10 years from the date of registration
Safety Issue:
Description:All toxicity grades and reportable adverse events will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

September 4, 2020