Trial record 1 of 1 for:
03959085
Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy
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| ClinicalTrials.gov Identifier: NCT03959085 |
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Recruitment Status :
Recruiting
First Posted : May 22, 2019
Last Update Posted : May 23, 2023
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Sponsor:
Children's Oncology Group
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group
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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, 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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| B Acute Lymphoblastic Leukemia B Lymphoblastic Lymphoma Central Nervous System Leukemia Mixed Phenotype Acute Leukemia Testicular Leukemia | Procedure: Biospecimen Collection Procedure: Bone Marrow Aspiration Procedure: Bone Marrow Biopsy Procedure: Bone Scan Drug: Calaspargase Pegol-mknl Procedure: Computed Tomography Drug: Cyclophosphamide Drug: Cytarabine Drug: Daunorubicin Hydrochloride Drug: Dexamethasone Drug: Doxorubicin Hydrochloride Biological: Inotuzumab Ozogamicin Drug: Leucovorin Calcium Procedure: Magnetic Resonance Imaging Drug: Mercaptopurine Drug: Methotrexate Drug: Pegaspargase Procedure: Positron Emission Tomography Drug: Prednisolone Other: Questionnaire Administration Radiation: Radiation Therapy Drug: Thioguanine Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 4772 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | October 28, 2019 |
| Estimated Primary Completion Date : | June 30, 2029 |
| Estimated Study Completion Date : | June 30, 2029 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Leukemia
Drug Information available for:
Inotuzumab ozogamicin
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (HR-FAV B-ALL)
See detailed description for Arm I
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy
Other Names:
Drug: Calaspargase Pegol-mknl Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV, IT, or SC
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Leucovorin Calcium Given PO or IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT or IV
Other Names:
Drug: Pegaspargase Given IV or IM
Other Names:
Drug: Prednisolone Given PO or IV
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Active Comparator: Arm II (HR B-ALL CONTROL)
See detailed description for Arm II.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy
Other Names:
Drug: Calaspargase Pegol-mknl Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV, IT, or SC
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Leucovorin Calcium Given PO or IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT or IV
Other Names:
Drug: Pegaspargase Given IV or IM
Other Names:
Drug: Prednisolone Given PO or IV
Other Names:
Other: Questionnaire Administration Ancillary studies Radiation: Radiation Therapy Undergo cranial radiation therapy
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm III (HR B-ALL EXPERIMENTAL)
See detailed description for Arm III.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy
Other Names:
Drug: Calaspargase Pegol-mknl Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV, IT, or SC
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Biological: Inotuzumab Ozogamicin Given IV
Other Names:
Drug: Leucovorin Calcium Given PO or IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT or IV
Other Names:
Drug: Pegaspargase Given IV or IM
Other Names:
Other: Questionnaire Administration Ancillary studies Radiation: Radiation Therapy Undergo cranial radiation therapy
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm IV (MPAL)
See detailed description for Arm IV.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy
Other Names:
Drug: Calaspargase Pegol-mknl Given IV
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV, IT, or SC
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Leucovorin Calcium Given PO or IV
Other Names:
Drug: Mercaptopurine Given PO
Other Names:
Drug: Methotrexate Given IT or IV
Other Names:
Drug: Pegaspargase Given IV or IM
Other Names:
Drug: Prednisolone Given PO or IV
Other Names:
Other: Questionnaire Administration Ancillary studies Radiation: Radiation Therapy Undergo testicular radiation therapy
Other Names:
Radiation: Radiation Therapy Undergo cranial radiation therapy
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: ARM V (B-LLY)
See detailed description for Arm V.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Procedure: Bone Marrow Aspiration Undergo bone marrow aspiration Procedure: Bone Marrow Biopsy Undergo bone marrow biopsy
Other Names:
Procedure: Bone Scan Undergo bone scan
Other Name: Bone Scintigraphy Drug: Calaspargase Pegol-mknl Given IV
Other Names:
Procedure: Computed Tomography Undergo CT
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Cytarabine Given IV, IT, or SC
Other Names:
Drug: Daunorubicin Hydrochloride Given IV
Other Names:
Drug: Dexamethasone Given PO or IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Leucovorin Calcium Given PO or IV
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI
Other Names:
Drug: Methotrexate Given IT or IV
Other Names:
Drug: Pegaspargase Given IV or IM
Other Names:
Procedure: Positron Emission Tomography Undergo PET
Other Names:
Drug: Prednisolone Given PO or IV
Other Names:
Other: Questionnaire Administration Ancillary studies Radiation: Radiation Therapy Undergo testicular radiation therapy
Other Names:
Radiation: Radiation Therapy Undergo cranial radiation therapy
Other Names:
Drug: Thioguanine Given PO
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- 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 [ Time Frame: From end of consolidation (EOC) to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years ]Power calculations are based on detecting an improvement in post consolidation DFS with the addition of InO to standard therapy for high risk (HR) B-acute lymphoblastic leukemia (ALL). All survival time analyses assume a Weibull distribution with shape parameter of 0.6 (based on historical data). Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using intent-to-treat (ITT) analysis based on randomized group.
Secondary Outcome Measures :
- 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 [ Time Frame: From EOC to first event (relapse, second malignant neoplasm, remission death) or date of last contact, assessed up to 5 years ]Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
- Incidence of adverse events for the integration of inotuzumab ozogamicin into the mBFM chemotherapy backbone in HR B-ALL [ Time Frame: Up to 5 years ]Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Will be monitored and reported.
- 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 plus pegaspargase (C-MTX) [ Time Frame: 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 ]Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
- 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 [ Time Frame: 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 ]Will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto. Estimation of treatment effect will be done using ITT analysis based on randomized group.
- Overall survival (OS) [ Time Frame: Time from study entry to death or date of last contact for those alive at last contact, assessed up to 5 years ]OS rates will be estimated using the Kaplan-Meier method and standard errors and confidence intervals estimated by the method of Peto.
Other Outcome Measures:
- Therapy administered to patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]Will be described.
- Disease response in patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]Will be described.
- Survival outcomes of patients with MPAL who come off protocol therapy due to poor disease response to ALL therapy [ Time Frame: Up to 5 years ]Will be described.
- Prevalence and significance of minimal marrow disease (MMD) at diagnosis and bone marrow MRD in disseminated B-LLy [ Time Frame: Up to 5 years ]Percentages with MMD at induction and MRD positivity at end of Induction will be described.
- Impact of four proposed interventions of varying intensities to enhance adherence to oral 6 mercaptopurine, with a randomization based upon baseline adherence measured during the first cycle of maintenance therapy [ Time Frame: Up to 5 years ]The main analyses will use mixed models including random effects to account for the multiple sites and longitudinal observations within patients. Will examine unadjusted associations of the primary outcome (MEMS-based adherence rate) with demographic, clinical and sociodemographic variables for the entire cohort (across 3 intervention arms). Those patient-level factors associated with the outcome will be included in the main model as fixed effects to improve the precision of the estimates. The basic model for adherence will include time and mean adherence during the baseline pre-intervention period and treatment group. It will also include interactions between time and both baseline adherence and intervention group to allow for intervention-specific trends and normal changes in adherence over time.
- DFS by sex [ Time Frame: Up to 5 years ]Estimates of DFS and the corresponding 95% confidence intervals by sex.
- DFS by race [ Time Frame: Up to 5 years ]Estimates of DFS and the corresponding 95% confidence intervals by race.
- DFS by ethnicity [ Time Frame: Up to 5 years ]Estimates of DFS and the corresponding 95% confidence intervals by ethnicity.
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| Ages Eligible for Study: | 1 Year to 25 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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 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
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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
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Age 1-9.99 years: WBC < 50,000/uL with:
- Testicular leukemia
- CNS leukemia (CNS3)
- Steroid pretreatment.
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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.
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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.
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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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03959085
Locations
Show 224 study locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Jennifer L McNeer | Children's Oncology Group |
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT03959085 |
| Other Study ID Numbers: |
AALL1732 NCI-2019-02845 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) AALL1732 ( Other Identifier: Children's Oncology Group ) AALL1732 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) |
| First Posted: | May 22, 2019 Key Record Dates |
| Last Update Posted: | May 23, 2023 |
| Last Verified: | January 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Acute Disease Neoplasms by Histologic Type Neoplasms Leukemia, Lymphoid Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Disease Attributes Pathologic Processes Calcium, Dietary Leucovorin Folic Acid |
Cytarabine Dexamethasone Dexamethasone acetate Prednisolone Methylprednisolone Acetate Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone acetate Hydrocortisone Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Hydrocortisone hemisuccinate Cyclophosphamide Doxorubicin Liposomal doxorubicin |