Trial Search Results

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

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.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Children's Oncology Group

Collaborator: National Cancer Institute (NCI)

Stanford Investigator(s):

Intervention(s):

  • Drug: Calaspargase Pegol-mknl
  • Drug: Cyclophosphamide
  • Drug: Cytarabine
  • Drug: Daunorubicin Hydrochloride
  • Drug: Dexamethasone
  • Drug: Doxorubicin Hydrochloride
  • Biological: Inotuzumab Ozogamicin
  • Drug: Leucovorin Calcium
  • Drug: Mercaptopurine
  • Drug: Methotrexate
  • Drug: Pegaspargase
  • Drug: Prednisolone
  • Other: Questionnaire Administration
  • Radiation: Radiation Therapy
  • Radiation: Radiation Therapy
  • Drug: Thioguanine
  • Drug: Vincristine Sulfate

Phase:

Phase 3

Eligibility


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.

Ages Eligible for Study

1 Year - 24 Years

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Stefania Ursu Chirita
650-723-1423
Recruiting