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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03959085




Registration number
NCT03959085
Ethics application status
Date submitted
20/05/2019
Date registered
22/05/2019
Date last updated
22/04/2024

Titles & IDs
Public title
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
Scientific 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
Secondary ID [1] 0 0
NCI-2019-02845
Secondary ID [2] 0 0
AALL1732
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B Acute Lymphoblastic Leukemia 0 0
B Lymphoblastic Lymphoma 0 0
Central Nervous System Leukemia 0 0
Mixed Phenotype Acute Leukemia 0 0
Testicular Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Biospecimen Collection
Treatment: Surgery - Bone Marrow Aspiration
Treatment: Surgery - Bone Marrow Biopsy
Treatment: Surgery - Bone Scan
Treatment: Drugs - Calaspargase Pegol
Treatment: Surgery - Computed Tomography
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cytarabine
Treatment: Drugs - Daunorubicin Hydrochloride
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Doxorubicin Hydrochloride
Other interventions - Inotuzumab Ozogamicin
Treatment: Drugs - Leucovorin Calcium
Treatment: Surgery - Magnetic Resonance Imaging
Treatment: Drugs - Mercaptopurine
Treatment: Drugs - Methotrexate
Treatment: Drugs - Pegaspargase
Treatment: Surgery - Positron Emission Tomography
Treatment: Drugs - Prednisolone
Other interventions - Questionnaire Administration
Treatment: Other - Radiation Therapy
Treatment: Other - Radiation Therapy
Treatment: Drugs - Thioguanine
Treatment: Drugs - Vincristine Sulfate

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

Active Comparator: Arm II (HR B-ALL CONTROL) - See detailed description for Arm II.

Experimental: Arm III (HR B-ALL EXPERIMENTAL) - See detailed description for Arm III.

Experimental: Arm IV (MPAL) - See detailed description for Arm IV.

Experimental: ARM V (B-LLY) - See detailed description for Arm V.


Treatment: Surgery: Biospecimen Collection
Undergo blood sample collection

Treatment: Surgery: Bone Marrow Aspiration
Undergo bone marrow aspiration

Treatment: Surgery: Bone Marrow Biopsy
Undergo bone marrow biopsy

Treatment: Surgery: Bone Scan
Undergo bone scan

Treatment: Drugs: Calaspargase Pegol
Given IV

Treatment: Surgery: Computed Tomography
Undergo CT

Treatment: Drugs: Cyclophosphamide
Given IV

Treatment: Drugs: Cytarabine
Given IV, IT, or SC

Treatment: Drugs: Daunorubicin Hydrochloride
Given IV

Treatment: Drugs: Dexamethasone
Given PO or IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Other interventions: Inotuzumab Ozogamicin
Given IV

Treatment: Drugs: Leucovorin Calcium
Given PO or IV

Treatment: Surgery: Magnetic Resonance Imaging
Undergo MRI

Treatment: Drugs: Mercaptopurine
Given PO

Treatment: Drugs: Methotrexate
Given IT or IV

Treatment: Drugs: Pegaspargase
Given IV or IM

Treatment: Surgery: Positron Emission Tomography
Undergo PET

Treatment: Drugs: Prednisolone
Given PO or IV

Other interventions: Questionnaire Administration
Ancillary studies

Treatment: Other: Radiation Therapy
Undergo testicular radiation therapy

Treatment: Other: Radiation Therapy
Undergo cranial radiation therapy

Treatment: Drugs: Thioguanine
Given PO

Treatment: Drugs: Vincristine Sulfate
Given IV
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Intervention code [3] 0 0
Other interventions
Intervention code [4] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Improvement in 5-year disease-free survival (DFS)
Timepoint [1] 0 0
From end of consolidation (EOC) to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years
Secondary outcome [2] 0 0
Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
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 MTX without leucovorin rescue + pegaspargase or calapargase pegol
Timepoint [3] 0 0
From study entry to first event (induction failure, Induction death, end of induction (EOI) minimal residual disease (MRD) >= 5%, EOC MRD >= 0.01%, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years
Secondary outcome [4] 0 0
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
Timepoint [4] 0 0
From study entry to first event (progressive disease, induction death, relapse, second malignancy, remission death) or date of last contact, assessed up to 5 years
Secondary outcome [5] 0 0
Overall survival (OS)
Timepoint [5] 0 0
Time from study entry to death or date of last contact for those alive at last contact, assessed up to 5 years

Eligibility
Key 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 days of enrollment for suspected
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 NOTE: Patients enrolled as suspected MPAL but found on
central confirmatory testing to have B-ALL must meet the B-ALL criteria above
(age, WBC, extramedullary disease, steroid pretreatment) to switch to the B-ALL
stratum before the end of induction.

- 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.

- Central nervous system (CNS) status must be determined prior to enrollment based on a
sample obtained prior to administration of any systemic or intrathecal chemotherapy,
except for steroid pretreatment and cytoreduction. It is recommended that intrathecal
cytarabine be administered at the time of the diagnostic lumbar puncture. This is
usually done at the time of the diagnostic bone marrow or venous line placement to
avoid a second lumbar puncture. This is allowed prior to enrollment. Systemic
chemotherapy must begin within 72 hours of this intrathecal therapy.

- 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.
Minimum age
1 Year
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 and steroid cytoreduction 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/03/2030
Actual
Sample size
Target
4997
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
John Hunter Children's Hospital - Hunter Regional Mail Centre
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [4] 0 0
Women's and Children's Hospital-Adelaide - North Adelaide
Recruitment hospital [5] 0 0
Monash Medical Center-Clayton Campus - Clayton
Recruitment hospital [6] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2310 - Hunter Regional Mail Centre
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5006 - North Adelaide
Recruitment postcode(s) [5] 0 0
3168 - Clayton
Recruitment postcode(s) [6] 0 0
6009 - Perth
Recruitment outside Australia
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United States of America
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Alabama
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United States of America
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Alaska
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Arizona
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Arkansas
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California
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Colorado
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Connecticut
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Delaware
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District of Columbia
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Florida
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
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Kentucky
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Louisiana
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Maine
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Maryland
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Massachusetts
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Michigan
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Mississippi
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Missouri
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Nebraska
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Nevada
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New Jersey
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New Mexico
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New York
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North Carolina
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North Dakota
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Ohio
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Oregon
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Pennsylvania
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Utah
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Vermont
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West Virginia
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Wisconsin
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Canada
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Alberta
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British Columbia
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Canada
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Manitoba
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Newfoundland and Labrador
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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New Zealand
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Auckland
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New Zealand
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Christchurch
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Puerto Rico
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Caguas
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Puerto Rico
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San Juan

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 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, to classify patients into post-consolidation treatment
groups. On the second part of this study, patients with HR B-ALL will receive the remainder
of the chemotherapy cycles (interim maintenance I, delayed intensification, interim
maintenance II, maintenance), with some patients randomized to receive inotuzumab. The
patients that receive inotuzumab will not receive part of delayed intensification. 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03959085
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jennifer L McNeer
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03959085