Trial Search Results

Combination Chemotherapy With or Without Blinatumomab in Treating Patients With Newly Diagnosed BCR-ABL-Negative B Lineage Acute Lymphoblastic Leukemia

This randomized phase III trial studies combination chemotherapy with blinatumomab to see how well it works compared to induction chemotherapy alone in treating patients with newly diagnosed breakpoint cluster region (BCR)-c-abl oncogene 1, non-receptor tyrosine kinase (ABL)-negative B lineage acute lymphoblastic leukemia. Drugs used in chemotherapy 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. Monoclonal antibodies, such as blinatumomab, may block cancer growth in different ways by targeting certain cells. It is not yet known whether combination chemotherapy is more effective with or without blinatumomab in treating newly diagnosed acute lymphoblastic leukemia.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

National Cancer Institute (NCI)

Intervention(s):

  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
  • Biological: Blinatumomab
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Etoposide
  • Other: Laboratory Biomarker Analysis
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisone
  • Biological: Rituximab
  • Drug: Vincristine Sulfate

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   - PRE-REGISTRATION

   - Diagnostic bone marrow and peripheral blood specimens must be submitted for
   immunophenotyping and selected molecular testing, and the establishment of BCR/ABL
   status; testing will be performed by the Eastern Cooperative Oncology Group
   (ECOG)-American College of Radiation Imaging Network (ACRIN) Leukemia Translational
   Research Laboratory (LTRL) and reported to the institution

      - NOTE: IT IS ESSENTIAL THAT A SAMPLE CONTAINING SUFFICIENT BLAST CELLS BE
      SUBMITTED TO THE ECOG-ACRIN LTRL AT BASELINE SO THAT SUBSEQUENT BONE MARROW
      ASSESSMENTS OF MRD CAN BE DONE; IN ADDITION TO ALLOWING THE LTRL TO CONFIRM
      ELIGIBILITY BASED ON BLAST CELL IMMUNOPHENOTYPE AND BCR/ABL STATUS, IT IS ALSO
      IMPERATIVE THAT AN ADEQUATE NUMBER OF BLASTS BE BANKED FOR ANALYSIS BY DRS
      MULLIGHAN/WILLMAN. WITHOUT ADEQUATE BASELINE SAMPLES, PATIENTS WILL NOT BE ABLE
      TO BE TREATED AND RANDOMIZED ON THIS PROTOCOL; IF A BONE MARROW ASPIRATE IS NOT
      AVAILABLE FOR LTRL SUBMISSION AT BASELINE, IT IS IMPERATIVE THAT DR PAIETTA FROM
      THE LTRL IS CALLED TO DISCUSS THE PERIPHERAL BLOOD WBC AND BLAST COUNT BEFORE
      BLOOD ONLY IS SUBMITTED

      - NOTE: Hydroxyurea can be given for up to 5 days prior to initiation of protocol
      therapy for control of leukocyte count and/or other symptoms or signs;
      corticosteroids can be given after pre-registration to the protocol and
      submission of baseline marrow and blood samples for control of leukocyte count
      and/or other symptoms or signs prior to initiation of protocol therapy if needed;
      if corticosteroids are given prior to pre-registration, contact the study chair
      as the patient may still be eligible to participate

   - INDUCTION ELIGIBILITY CRITERIA-STEP 1

   - New diagnosis of B lineage ALL must be made upon bone marrow or peripheral blood
   immunophenotyping; cases with myeloid antigen expression, but unequivocal lymphoid
   immunophenotype, are eligible

   - Mature B ALL (Burkitt's-like leukemia) is excluded from enrollment in this trial;
   pre-study bone marrow biopsy and aspirate must be completed =< 1 week prior to
   registration

   - Negativity for the Philadelphia chromosome must be established by conventional
   cytogenetics, fluorescence in situ hybridization (FISH) and/or polymerase chain
   reaction (PCR); patients who are negative for the Philadelphia chromosome by
   conventional cytogenetics must have FISH or PCR performed for BCR/ABL to exclude
   occult translocations

   - Cytogenetic analysis must be performed from diagnostic bone marrow (preferred) or if
   adequate number of circulating blasts from peripheral blood; FISH testing for common
   B-lineage ALL abnormalities including t(9;22) (BCR/ABL1), t(12;21) (ETS-variant gene 6
   [ETV6]/runt-related transcription factor 1 [RUNX1]), t(1;19) (pre-B-cell leukemia
   homeobox 1 [PBX1]/transcription factor 3 [TCF3]), +4,+10,+17, (centromeric
   [Cen]4/Cen10/Cen17), t(11q23;var), (myeloid/lymphoid or mixed lineage leukemia [MLL]),
   deletion (del)(9p) (cyclin-dependent kinase inhibitor 2A [CDKN2A]/Cen9), and t(14;var)
   (immunoglobulin heavy chain [IGH] is encouraged); if there are few or no circulating
   blasts and an adequate marrow sample cannot be obtained for cytogenetic analysis, the
   patient may still enroll on the trial

   - Patient must not have a concurrent active malignancy for which they are receiving
   treatment

   - Serum direct bilirubin < 2 mg/dl or serum total bilirubin =< 3; NOTE: the above
   stipulation for normal hepatic function does not apply if liver dysfunction is due to
   leukemia infiltration

   - Serum creatinine < 2 mg/dl; NOTE: the above stipulation for normal hepatic function
   does not apply if liver dysfunction is due to leukemia infiltration

   - Patient should be human leukocyte antigen (HLA) typed (A, B, C, DR and DQ) during
   induction therapy phase or a written explanation for not undergoing HLA typing on the
   flow sheet

   - Patient must not have intercurrent organ damage or medical problems that will
   jeopardize the outcome of therapy (i.e., psychiatric disorder, drug abuse, pregnancy)

   - Patients with known human immunodeficiency virus (HIV) infection are eligible if they
   meet all of the following criteria:

      - No history of acquired immune deficiency syndrome (AIDS)-related complications
      other than a history of low CD4+ T-cell count (< 200/mm^3) prior to initiation of
      combination antiretroviral therapy; on study CD4+ T-cell count may not be
      informative due to leukemia and should not be used as an exclusion criterion if
      low

      - Patient must be healthy on the basis of HIV disease with high likelihood of near
      normal life span were it not for the leukemia

      - Patient must have serum HIV viral load of < 200 copies/mm^3

      - Patient must be on combination antiretroviral therapy with minimal
      pharmacokinetic interactions with study therapy and minimal overlapping clinical
      toxicity with protocol therapy

      - Patient must not be receiving protease inhibitors or once daily formulations
      containing cobicistat, stavudine, or on regimens containing stavudine or
      zidovudine

      - It is recommended to utilize a regimen of the integrase inhibitor, dolutegravir,
      combined with either disoproxil fumarate/emtricitabine or dolutegravir combined
      with tenofovir alafenamide/emtricitabine

   - Patient must not have an antecedent hematologic disorder

   - Patient must have no history of recent myocardial infarction (within three months),
   uncontrolled congestive heart failure, or uncontrolled cardiac arrhythmia

   - Patient must not have a history or presence of clinically relevant central nervous
   system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe
   brain injuries, dementia; Parkinson's disease, cerebellar disease, organic brain
   syndrome, psychosis, or other significant CNS abnormalities

   - Patient must have a normal cardiac ejection fraction by pretreatment multigated
   acquisition scan (MUGA) or echocardiogram within 4 weeks prior to registration
   (resting ejection fraction >= 40% or >= 5% increase with exercise), shortening
   fraction by echocardiogram >= 24%, or to within the normal range of values for the
   institution

   - Patient must not have an active uncontrolled infection

   - Women must not be pregnant or breast-feeding and must not become pregnant or
   breastfeed during protocol therapy and for at least 3 months after protocol therapy;
   woman of childbearing potential must abstain from sexual activity or be willing to use
   2 highly effective forms of contraception throughout protocol therapy and for at least
   an additional 3 months after the last dose of protocol-specified therapy; all females
   of childbearing potential must have a blood test or urine study within 2 weeks prior
   to registration to rule out pregnancy; a female of childbearing potential is any
   woman, regardless of sexual orientation or whether they have undergone tubal ligation,
   who meets the following criteria: has not undergone a hysterectomy or bilateral
   oophorectomy; or has not been naturally postmenopausal for at least 24 consecutive
   months (i.e., has had menses at any time in the preceding 24 consecutive months)

   - Men who have a female partner of childbearing potential must be willing to use 2
   highly effective forms of contraception throughout protocol therapy and for at least
   an additional 3 months after the last dose of protocol-specified therapy; men who have
   a pregnant partner must be willing to use a condom during sexual activity throughout
   protocol therapy and for 3 months after the last dose of protocol-specified therapy

   - ECOG performance score 0-3

   - Patient must have given written informed consent

   - POST-INDUCTION THERAPY ELIGIBILITY CRITERIA (PRIOR TO INTENSIFICATION-STEP 2)

   - ECOG performance status 0-2

   - Patients must have achieved a CR or CRi

   - Patients who have achieved a CR or CRi must have maintained peripheral blood evidence
   of a CR or CRi

   - Patient must be CNS (cerebrospinal fluid [CSF]) negative for leukemia

   - Patients must have resolved any serious infectious complications related to induction

   - Any significant medical complications related to induction must have resolved

   - Obtained =< 48 hours prior to registration: Serum creatinine =< 2.0 mg/dl

   - Obtained =< 48 hours prior to registration: Serum direct bilirubin < 2 mg/dL or serum
   total bilirubin =< 3

   - Obtained =< 48 hours prior to registration: Aspartate aminotransferase (AST) and
   alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)

   - RANDOMIZATION TO BLINATUMOMAB OR NO BLINATUMOMAB-STEP 3

   - Patients must have an ECOG performance status of 0-2

   - Patients must have maintained peripheral blood evidence of a remission and must have a
   CR or CRi, confirmed on restaging bone marrow (BM) aspirate and biopsy

   - Patients must have resolved any serious infectious complications related to therapy

   - Any significant medical complications related to therapy must have resolved

   - Direct or total bilirubin < 1.5 x ULN (unless related to Gilbert's or Meulengracht's
   syndrome); the values must be obtained within 48 hours prior to randomization

   - Serum creatinine < 1.5 x ULN; the values must be obtained within 48 hours prior to
   randomization

   - Bone marrow aspirates must be submitted for centralized minimal residual disease (MRD)
   assessment performed by the ECOG-ACRIN Leukemia Translational Research Laboratory

   - MRD results will be reported to the submitting institution

      - NOTE: FOR MRD ASSESSMENTS, AN ASPIRATE FROM A SEPARATE BONE MARROW ASPIRATION
      SITE MUST BE SUBMITTED (THE NEEDLE CAN BE RE-DIRECTED THROUGH THE SAME SKIN
      PUNCTURE SITE); ONLY SUBMIT ASPIRATES FROM THE FIRST PULL OF AN ASPIRATION SITE
      FOR MRD TESTING; DO NOT SUBMIT SAMPLES FROM THE SECOND OR THIRD PULL OF THE SAME
      ASPIRATION SITE

      - In B-lineage ALL, MRD levels in peripheral blood or from a dilute marrow
      aspiration can be 300% lower, on average, than those in bone marrow at a given
      time point; submitting a first pull from a separate aspiration site will ensure
      that MRD determinations used in randomization and trial interpretation are
      accurate

         - NOTE: failure to submit bone marrow aspirates will result in a major
         violation at the time of an audit

   - CRITERIA FOR ALLOGENEIC TRANSPLANTATION

   - A suitable donor must be identified; there are no restrictions on donor type and can
   include a matched sibling, a matched or mismatched unrelated donor, a family haplotype
   matched donor or a cord blood donor (single or double)

   - Patients should meet the eligibility criteria for RANDOMIZATION TO BLINATUMOMAB OR NO
   BLINATUMOMAB-STEP 3

   - Patients must be considered reliable enough to comply with the medication regimen and
   follow-up, and have social support necessary to allow this compliance

   - CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have an ECOG performance status
   of 0-3

   - CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have maintained peripheral
   blood evidence of a remission and must have a CR or CRi, confirmed on restaging BM
   aspirate and biopsy

   - CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Patients must have resolved any serious
   infectious complications related to therapy

   - CRITERIA FOR MAINTENANCE THERAPY-STEP 4: Any significant medical complications related
   to therapy must have resolved

Ages Eligible for Study

30 Years - 70 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kellie Baumann
650-723-4547
Recruiting