Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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 or calaspargase pegol 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.
Phase
Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Pediatric Cancer
Enrollment 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 22 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.
- Patients must be > 365 days and < 25 years of age
- 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.