Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

Brief Title

Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy

Official Title

A Phase 3 Randomized Trial of Inotuzumab Ozogamicin (NSC#: 772518) for Newly Diagnosed High-Risk B-ALL; Risk-Adapted Post-Induction Therapy for High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and Disseminated B-LLy

Brief Summary

      This phase III trial studies whether inotuzumab ozogamicin added to post-induction
      chemotherapy for patients with High-Risk B-cell Acute Lymphoblastic Leukemia (B-ALL) improves
      outcomes. This trial also studies the outcomes of patients with mixed phenotype acute
      leukemia (MPAL), and B-lymphoblastic lymphoma (B-LLy) when treated with ALL therapy without
      inotuzumab ozogamicin. Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab,
      linked to a type of chemotherapy called calicheamicin. Inotuzumab attaches to cancer cells in
      a targeted way and delivers calicheamicin to kill them. Other drugs used in the chemotherapy
      regimen, such as cyclophosphamide, cytarabine, dexamethasone, doxorubicin, daunorubicin,
      methotrexate, leucovorin, mercaptopurine, prednisone, thioguanine, vincristine, and
      pegaspargase 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. This trial will
      also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and
      disseminated B lymphoblastic lymphoma (B-LLy) when treated with high-risk ALL chemotherapy.

      The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard
      of care chemotherapy maintains or improves outcomes in High Risk B-cell Acute Lymphoblastic
      Leukemia (HR B-ALL). The first part of the study includes the first two phases of therapy:
      Induction and Consolidation. This part will collect information on the leukemia, as well as
      the effects of the initial treatment, in order to classify patients into post-consolidation
      treatment groups. On the second part of this study, patients will receive the remainder of
      the chemotherapy cycles (interim maintenance I, delayed intensification, interim maintenance
      II, maintenance), with some patients randomized to receive inotuzumab. Other aims of this
      study include investigating whether treating both males and females with the same duration of
      chemotherapy maintains outcomes for males who have previously been treated for an additional
      year compared to girls, as well as to evaluate the best ways to help patients adhere to oral
      chemotherapy regimens. Finally, this study will be the first to track the outcomes of
      subjects with disseminated B-cell Lymphoblastic Leukemia (B LLy) or Mixed Phenotype Acute
      Leukemia (MPAL) when treated with B-ALL chemotherapy.
    

Detailed Description

      PRIMARY OBJECTIVE:

      I. To determine in a randomized manner if the addition of 2 blocks of inotuzumab ozogamicin
      to modified Berlin-Frankfurt-Munster (mBFM) chemotherapy will improve 5-year disease-free
      survival (DFS) in children and young adults with high-risk B-cell acute lymphoblastic
      leukemia (HR B-ALL).

      SECONDARY OBJECTIVES:

      I. To describe the 5-year DFS for a favorable risk subset of National Cancer Institute (NCI)
      HR B-ALL (HR-Fav) when treated with mBFM chemotherapy with a single high-dose methotrexate
      (HD-MTX) interim maintenance (IM) phase and treatment duration of 2 years from the start of
      IM regardless of sex.

      II. To determine the toxicity and tolerability of inotuzumab ozogamicin integrated into the
      mBFM chemotherapy backbone in HR B-ALL.

      III. To describe the 5-year event-free survival (EFS) for patients with mixed phenotype acute
      leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second IM phase with Capizzi
      escalating intravenous (IV) methotrexate (MTX) without leucovorin rescue plus pegaspargase
      (C-MTX).

      IV. To describe the 5-year EFS for patients with disseminated (Murphy stage III-IV) B-cell
      lymphoblastic lymphoma (B-LLy) receiving mBFM HR B-ALL therapy that includes a second IM
      phase with C-MTX.

      EXPLORATORY OBJECTIVES:

      I. To describe the therapy administered, disease response, and survival outcomes of patients
      with MPAL who come off protocol therapy due to poor disease response to ALL therapy either
      during Induction, at end of induction (EOI), or at end of consolidation (EOC).

      II. To define the prevalence and significance of minimal marrow disease (MMD) at diagnosis
      and bone marrow minimal residual disease (MRD) at EOI in disseminated B-LLy.

      III. To determine the impact of proposed adherence-enhancing interventions on adherence to
      oral 6-mercaptopurine in patients with ALL.

      OUTLINE: All patients receive the same Induction and Consolidation chemotherapy. Patients
      with HR-Fav B-ALL are assigned to Arm I. Patients with HR B-ALL are randomized to Arm II or
      III. Patients with MPAL are assigned to Arm IV, and patients with B-LLy are assigned to Arm
      V.

      All patients with B-ALL receive Induction and Consolidation therapy:

      INDUCTION: Patients receive cytarabine intrathecally (IT) on day 1 and central nervous system
      (CNS)2 patients also receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also
      receive vincristine intravenously (IV) or IV push over 1 minute on days 1, 8, 15, and 22,
      daunorubicin IV over 1-15 minutes days 1, 8, 15, and 22, pegaspargase intramuscularly (IM) or
      IV over 1-2 hours on day 4, and methotrexate IT on days 8 and 29 (and on days 15 and 22 for
      CNS3 patients). Patients < 10 years old receive dexamethasone orally (PO) twice daily (BID)
      or IV on days 1-14; patients >= 10 years old receive prednis(ol)one PO BID or IV on days
      1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable
      toxicity.

      CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
      cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39,
      mercaptopurine PO once daily (QD) on days 1-14 and 29-42, and methotrexate IT on days 1, 8,
      15, and 22 (CNS3 patients receive methotrexate IT on days 1 and 8). Patients also receive
      vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and pegaspargase IV over
      1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in the absence of disease
      progression or unacceptable toxicity. Additionally, patients with testicular disease at
      diagnosis that does not resolve by the end of induction will undergo radiation therapy over
      12 once daily fractions.

      POST-CONSOLIDATION THERAPY: After Consolidation, based on clinical features and response,
      patients with B-ALL are designated as HR-Fav or HR B-ALL. Patients with HR-Fav B-ALL are
      assigned to Arm I. Patients with HR B-ALL are randomized to Arm II or III. Patients with MPAL
      and B-LLy are assigned to therapy arms (Arms IV and V) that are identical to Arm II. Patients
      that are < 10 years, have CNS1, no testicular leukemia, with favorable cytogenetics (ETV6
      RUNX1 fusion or double trisomies [4 and 10]), =< 24 hours of steroids in the two weeks prior
      to diagnosis, and EOI MRD < 0.01% are assigned to Arm I. Patients with HR B-ALL who are
      surface CD22 positive at diagnosis and have MRD < 0.01% by the end of Consolidation, are
      randomized to either Arm II or III.

      ARM I: HR-FAV B-ALL (Patients that are < 10 years, have CNS1 status, no testicular leukemia,
      with favorable cytogenetics (ETV6 RUNX1 fusion or double trisomies [4 and 10]), =< 24 hours
      of steroids in the two weeks prior to diagnosis, and EOI MRD < 0.01%)

      INTERIM MAINTENANCE: Patients receive vincristine IV or IV push over 1 minute on days 1, 15,
      29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO
      or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO QD on days 1-14, 15-28, 29-42,
      and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 9 weeks in the
      absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO
      BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and
      15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase
      IV over 1-2 hours or IM on day 4. Treatment (Parts I and II of Delayed Intensification)
      continues for 8 weeks in the absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on
      day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and
      36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43
      and 50, and pegaspargase IV over 1-2 hours or IM on day 43. Treatment (Parts I and II of
      Delayed Intensification) continues for 8 weeks in the absence of disease progression or
      unacceptable toxicity.

      MAINTENANCE: Patients receive methotrexate IT on days 1 and 29 for cycles 1-4, and day 1 for
      subsequent cycles. Patients also receive vincristine IV or IV push over 1 minute on day 1,
      prednisolone PO BID or IV on days 1-5, mercaptopurine PO QD on days 1-84, and methotrexate PO
      on days 8, 15, 22, (29 excluded in cycles 1-4), 36, 43, 50, 57, 64, 71, and 78. Cycles repeat
      every 12 weeks for up to 2 years in the absence of disease progression or unacceptable
      toxicity.

      Patients with HR B-ALL who have MRD < 0.01% by the end of Consolidation, and leukemic blasts
      positive for surface CD22 at diagnosis are randomized to Arm II or Arm III.

      ARM II: HR B-ALL (CONTROL) INTERIM MAINTENANCE I: Patients receive vincristine IV or IV push
      over 1 minute on days 1, 15, 29 and 43, high dose methotrexate IV over 24 hours on days 1,
      15, 29 and 43, leucovorin PO or IV on days 3-4, 17-18, 31-32, 45-46, mercaptopurine PO QD on
      days 1-14, 15-28, 29-42, and 43-56, and methotrexate IT on days 1 and 29. Treatment continues
      for 9 weeks in the absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO
      BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and
      15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase
      IV over 1-2 hours or IM on day 4. Treatment (Parts I and II of Delayed Intensification)
      continues for 8 weeks in the absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on
      day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and
      36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43
      and 50, and pegaspargase IV over 1-2 hours or IM on day 43. Treatment (Parts I and II of
      Delayed Intensification) continues for 8 weeks in the absence of disease progression or
      unacceptable toxicity.

      INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1,
      11, 21, 31 and 41, methotrexate IV over 2-15 minutes or 10-15 minutes on days 1, 11, 21, 31,
      and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or IM on days 2
      and 22. Treatment continues for 8 weeks in the absence of disease progression or unacceptable
      toxicity.

      ARM III: HR B-ALL (EXPERIMENTAL) INOTUZUMAB OZOGAMICIN (InO) BLOCK 1: Patients receive
      inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 and methotrexate IT on day 1.
      Treatment continues for 4 weeks in the absence of disease progression or unacceptable
      toxicity.

      INTERIM MAINTENANCE I: Patients receive vincristine IV or IV push over 1 minute on days 1,
      15, 29 and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin
      PO or IV on days 3-4, 17-18, 31-32, and 45-46, mercaptopurine PO on days 1-14, 15-28, 29-42,
      and 43-56, and methotrexate IT on days 1 and 29. Treatment continues for 9 weeks in the
      absence of disease progression or unacceptable toxicity.

      InO BLOCK 2: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15.
      Treatment continues for 4 weeks in the absence of disease progression or unacceptable
      toxicity.

      DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO
      BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and
      15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase
      IV over 1-2 hours or IM on day 4. Treatment (Parts I and II of Delayed Intensification)
      continues for 8 weeks in the absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on
      day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and
      36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43
      and 50, and pegaspargase IV over 1-2 hours or IM on day 43. Treatment (Parts I and II of
      Delayed Intensification) continues for 8 weeks in the absence of disease progression or
      unacceptable toxicity.

      INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1,
      11, 21, 31, and 41, methotrexate IV on days 1, 11, 21, 31, and 41, methotrexate IT on days 1
      and 31, and pegaspargase IV over 1-2 hours or IM on days 2 and 22. Treatment continues for 8
      weeks in the absence of disease progression or unacceptable toxicity.

      ARMS II AND III: HR B-ALL MAINTENANCE: Patients receive vincristine IV or IV push over 1
      minute on day 1, prednisolone PO BID or IV on days 1-5, mercaptopurine PO on days 1-84,
      methotrexate PO on days 8, 15, 22, 29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71
      and 78, and methotrexate IT on days 1 (and 29 of cycles 1-2 for patients who do not receive
      cranial radiation). Cycles repeat every 12 weeks for up to 2 years in the absence of disease
      progression or unacceptable toxicity. Patients with CNS3 disease undergo cranial radiation
      therapy over 10 fractions during the first 4 weeks.

      ARM IV: MPAL INDUCTION: Patients receive cytarabine IT on day 1 and CNS2 patients also
      receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also receive vincristine IV or
      IV push over 1 minute on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8,
      15, and 22, pegaspargase IM or IV over 1-2 hours on day 4, and methotrexate IT on days 8 and
      29 (and on days 15 and 22 for CNS3 patients). Patients < 10 years old receive dexamethasone
      PO BID or IV on days 1-14; patients >= 10 years old receive prednisolone PO BID or IV on days
      1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable
      toxicity.

      CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
      cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO
      on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22
      for CNS3 patients), vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and
      pegaspargase IV over 1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in
      the absence of disease progression or unacceptable toxicity. Patients with testicular disease
      at diagnosis that does not resolve by the end of induction will and continued evidence of
      testicular disease at end of induction undergo testicular radiation over 12 once-daily
      fractions.

      ARM V: B-LLY INDUCTION: Patients receive cytarabine IT on day 1 and CNS2 patients also
      receive cytarabine IT on days 4, 5 or 6 and 11 or 12. Patients also receive vincristine IV or
      IV push over 1 minute on days 1, 8, 15, and 22, daunorubicin IV over 1-15 minutes days 1, 8,
      15, and 22, pegaspargase IM or IV over 1-2 hours on day 4, and methotrexate IT on days 8 and
      29 (and on days 15 and 22 for CNS3 patients). Patients < 10 years old receive dexamethasone
      PO BID or IV on days 1-14; patients >= 10 years old receive prednisolone PO BID or IV on days
      1-28. Treatment continues for 5 weeks in the absence of disease progression or unacceptable
      toxicity.

      CONSOLIDATION: Patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29,
      cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO
      on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22 (excluded on days 15 and 22
      CNS3 patients), vincristine IV or IV push over 1 minute on days 15, 22, 43, and 50, and
      pegaspargase IV over 1-2 hours or IM on days 15 and 43. Treatment continues for 8 weeks in
      the absence of disease progression or unacceptable toxicity. Patients with testicular disease
      at diagnosis that does not resolve by the end of induction will and continued evidence of
      testicular disease at end of induction undergo testicular radiation therapy over 12
      once-daily fractions.

      ARM IV AND V: MPAL AND B-LLY (Post-Consolidation Therapy) INTERIM MAINTENANCE I: Patients
      receive vincristine IV or IV push over 1 minute on days 1, 15, 29, and 43, high dose
      methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin PO or IV on days 3-4,
      17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29 and mercaptopurine PO QD on days
      1-14, 15-28, 29-42, and 43-56. Treatment continues for 9 weeks in the absence of disease
      progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART I): Patients receive methotrexate IT on day 1, dexamethasone PO
      BID or IV on days 1-7 and 15-21, vincristine IV or IV push over 1 minute on days 1, 8, and
      15, doxorubicin IV over 1-15 minutes or up to 1 hour on days 1, 8, and 15, and pegaspargase
      IV over 1-2 hours or IM on day 4. Treatment (Parts I and II of Delayed Intensification)
      continues for 8 weeks in the absence of disease progression or unacceptable toxicity.

      DELAYED INTENSIFICATION (PART II): Patients receive cyclophosphamide IV over 30-60 minutes on
      day 29, thioguanine PO on days 29-42, cytarabine IV over 1-30 minutes or SC on days 29-32 and
      36-39, methotrexate IT on days 29 and 36, vincristine IV or IV push over 1 minute on days 43
      and 50, and pegaspargase IV over 1-2 hours or IM on day 43. Treatment (Parts I and II of
      Delayed Intensification) continues for 8 weeks in the absence of disease progression or
      unacceptable toxicity.

      INTERIM MAINTENANCE II: Patients receive vincristine IV or IV push over 1 minute on days 1,
      11, 21, 31, and 41, methotrexate IV or infusion over 2-15 minutes or 10-15 minutes on days 1,
      11, 21, 31, and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours or
      IM on days 2 and 22. Treatment continues for 8 weeks in the absence of disease progression or
      unacceptable toxicity.

      MAINTENANCE: Patients receive vincristine IV or IV push over 1 minute on days 1, prednisolone
      PO BID or IV on days 1-5, mercaptopurine PO on days 1-84, methotrexate PO on days 8, 15, 22,
      29 (excluded in cycles 1 and 2), 36, 43, 50, 57, 64, 71, and 78, and methotrexate IT on days
      1 (and 29 of cycles 1-2 for patients who do not receive cranial radiation). Cycles repeat
      every 12 weeks for up to 2 years in the absence of disease progression or unacceptable
      toxicity. Patients with CNS3 disease at diagnosis undergo cranial radiation therapy for 10
      fractions over 4 weeks.

      After completion of study treatment, patients are followed up at 4 weeks, then every 3 months
      for 2 years, every 4-6 months for the third year, then every 6-12 months for years 4-5.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Improvement in 5-year disease-free survival (DFS) after adding 2 blocks of inotuzumab ozogamicin (InO) to Berlin-Frankfurt-Munster (mBFM) chemotherapy in children and young adults with High-Risk (HR) B-ALL

Secondary Outcome

 5-year DFS for favorable risk subset of NCI HR B-ALL (HR favorable) when treated with mBFM chemotherapy with a single high-dose methotrexate (HD MTX) Interim Maintenance (IM) phase and treatment duration of 2 years from the start of IM regardless of sex

Condition

B Acute Lymphoblastic Leukemia

Intervention

Cyclophosphamide

Study Arms / Comparison Groups

 Arm I (HR-FAV B-ALL)
Description:  See detailed description for Arm I

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

3698

Start Date

October 28, 2019

Completion Date

May 31, 2027

Primary Completion Date

May 31, 2027

Eligibility Criteria

        Inclusion Criteria:

          -  B-ALL and MPAL patients must be enrolled on APEC14B1 and consented to eligibility
             studies (Part A) prior to treatment and enrollment on AALL1732. Note that central
             confirmation of MPAL diagnosis must occur within 7 business days after enrollment for
             MPAL patients. If not performed within this time frame, patients will be taken off
             protocol.

          -  APEC14B1 is not a requirement for B-LLy patients but for institutional compliance
             every patient should be offered participation in APEC14B1. B-LLy patients may directly
             enroll on AALL1732.

          -  White blood cell count (WBC) criteria for patients with B-ALL (within 7 days prior to
             the start of protocol-directed systemic therapy):

               -  Age 1-9.99 years: WBC >= 50,000/uL

               -  Age 10-24.99 years: Any WBC

               -  Age 1-9.99 years: WBC < 50,000/uL with:

                    -  Testicular leukemia

                    -  CNS leukemia (CNS3)

                    -  Steroid pretreatment.

          -  White blood cell count (WBC) criteria for patients with MPAL (within 7 days prior to
             the start of protocol-directed systemic therapy):

               -  Age 1-24.99 years: any WBC.

          -  Patient has newly diagnosed B-ALL or MPAL (by World Health Organization [WHO] 2016
             criteria) with > 25% blasts on a bone marrow (BM) aspirate;

               -  OR If a BM aspirate is not obtained or is not diagnostic of acute leukemia, the
                  diagnosis can be established by a pathologic diagnosis of acute leukemia on a BM
                  biopsy;

               -  OR A complete blood count (CBC) documenting the presence of at least 1,000/uL
                  circulating leukemic cells if a bone marrow aspirate or biopsy cannot be
                  performed.

          -  Patient has newly diagnosed B-LLy Murphy stages III or IV.

          -  Patient has newly diagnosed B-LLy Murphy stages I or II with steroid pretreatment.

          -  Note: For B-LLy patients with tissue available for flow cytometry, the criterion for
             diagnosis should be analogous to B-ALL. For tissue processed by other means (i.e.,
             paraffin blocks), the methodology and criteria for immunophenotypic analysis to
             establish the diagnosis of B-LLy defined by the submitting institution will be
             accepted.

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent.

          -  All institutional, Food and Drug Administration (FDA), and NCI requirements for human
             studies must be met.

        Exclusion Criteria:

          -  Patients with Down syndrome are not eligible (patients with Down syndrome and B-ALL
             are eligible for AALL1731, regardless of NCI risk group).

          -  With the exception of steroid pretreatment or the administration of intrathecal
             cytarabine, patients must not have received any prior cytotoxic chemotherapy for the
             current diagnosis of B-ALL, MPAL, or B-LLy or for any cancer diagnosed prior to
             initiation of protocol therapy on AALL1732.

          -  Patients who have received > 72 hours of hydroxyurea within one week prior to start of
             systemic protocol therapy.

          -  Patients with B-ALL or MPAL who do not have sufficient diagnostic bone marrow
             submitted for APEC14B1 testing and who do not have a peripheral blood sample submitted
             containing > 1,000/uL circulating leukemia cells.

          -  Patients with acute undifferentiated leukemia (AUL) are not eligible.

          -  For Murphy stage III/IV B-LLy patients, or stage I/II patients with steroid
             pretreatment, the following additional exclusion criteria apply:

               -  T-lymphoblastic lymphoma.

               -  Morphologically unclassifiable lymphoma.

               -  Absence of both B-cell and T-cell phenotype markers in a case submitted as
                  lymphoblastic lymphoma.

          -  Patients with known Charcot-Marie-Tooth disease.

          -  Patients with known MYC translocation associated with mature (Burkitt) B-cell ALL,
             regardless of blast immunophenotype.

          -  Patients requiring radiation at diagnosis.

          -  Female 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.

          -  Lactating women who plan to breastfeed their infants while on study and for 2 months
             after the last dose of inotuzumab ozogamicin.

          -  Sexually active patients of reproductive potential who have not agreed to use an
             effective contraceptive method for the duration of study participation. For those
             patients randomized to inotuzumab ozogamicin, there is a minimum of 8 months after the
             last dose of inotuzumab ozogamicin for females and 5 months after the last dose of
             inotuzumab ozogamicin for males.
      

Gender

All

Ages

1 Year - 24 Years

Accepts Healthy Volunteers

No

Contacts

Jennifer L McNeer, , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT03959085

Organization ID

AALL1732

Secondary IDs

NCI-2019-02845

Responsible Party

Sponsor

Study Sponsor

Children's Oncology Group

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Jennifer L McNeer, Principal Investigator, Children's Oncology Group


Verification Date

December 2020