Phase 3
N=1,645
Bortezomib and Sorafenib Tosylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Acute Myeloid Leukemia · Leukemia Cutis · Myeloid Neoplasm · Myeloid Sarcoma
Bottom Line
View on ClinicalTrials.gov: NCT01371981 ↗Enrolled (actual)
1,645
Serious AEs
27.5%
Results posted
Jul 2020
Primary outcome: Primary: Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations — 45.64; 46.95 percentage of patients
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Asparaginase (Drug); Bortezomib (Drug); Cytarabine (Drug); Daunorubicin Hydrochloride (Drug); Etoposide (Drug); Laboratory Biomarker Analysis (Other); Mitoxantrone Hydrochloride (Drug); Pharmacological Study (Other); Quality-of-Life Assessment (Other); Questionnaire Administration (Other); Sorafenib Tosylate (Drug)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Event-free Survival (EFS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations |
45.64; 46.95 | — |
| PRIMARY EFS for Patients on Arm C, Cohort 1 |
25.00 | — |
| PRIMARY EFS for Patients on Arm C, Cohort 2 |
56.12 | — |
| PRIMARY EFS for Patients on Arm C, Cohort 3 |
58.18 | — |
| SECONDARY Overall Survival (OS) for Patients Without High Allelic Ratio FLT3/ITD+ Mutations |
65.04; 68.45 | — |
| SECONDARY OS for Patients on Arm C, Cohort 1 |
41.67 | — |
| SECONDARY OS for Patients on Arm C, Cohort 2 |
64.77 | — |
| SECONDARY OS for Patients on Arm C, Cohort 3 |
61.84 | — |
| SECONDARY Relapse Rate for Patients Without High Allelic Ratio FLT3/ITD+ Mutations |
46.67; 46.65 | — |
| SECONDARY Proportion of Patients Experiencing Grade 3 or Higher Non-hematologic Toxicities and Infections While on Protocol Therapy |
0.8819; 0.9217; 0.9167; 0.9394; 0.9149; 0.0239 | — |
| SECONDARY Proportion of High Risk Children Without HR FLT3/ITD+ Converting From Positive MRD at End of Induction I to Negative MRD at the End of Induction II |
0.5000; 0.5238 | — |
| SECONDARY Total Scale Score From Parent-reported Pediatric Quality of Life Inventory Module |
68.3; 67.8; 71.3; 61.6 | — |
| SECONDARY Total Scale Score From Parent-reported Cancer Module |
66.2; 65.8; 74.9; 63.7 | — |
| SECONDARY Total Scale Score From Parent-reported Multidimensional Fatigue Scale Module |
60.5; 58.1; 71.2; 48.2 | — |
| SECONDARY Bortezomib Clearance |
8.42 | — |
| SECONDARY Sorafenib Steady State Concentration |
1090.0 | — |
| SECONDARY Change in Shortening Fraction |
-1.8445; -2.6298; -2.2333; -3.6700; -3.4246 | — |
| SECONDARY Change in Ejection Fraction |
-2.0272; -2.3453; -7.5000; -5.1997; -3.4624 | — |
| SECONDARY Serum Concentrations of GVHD Biomarker |
— | — |
Summary
This randomized phase III trial studies how well bortezomib and sorafenib tosylate work in treating patients with newly diagnosed acute myeloid leukemia. Bortezomib and sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving bortezomib and sorafenib tosylate together with combination chemotherapy may be an effective treatment for acute myeloid leukemia.
Eligibility Criteria
Inclusion Criteria
- Patients must be newly diagnosed with de novo acute myelogenous leukemia
- Patients with previously untreated primary AML who meet the customary criteria for AML with >= 20% bone marrow blasts as set out in the 2008 World Health Organization (WHO) Myeloid Neoplasm Classification are eligible
- Attempts to obtain bone marrow either by aspirate or biopsy must be made unless clinically prohibitive; in cases where it is clinically prohibitive, peripheral blood with an excess of 20% blasts and in which adequate flow cytometric and cytogenetics/fluorescent in situ hybridization (FISH) testing is feasible can be substituted for the marrow exam at diagnosis
- Patients with < 20% bone marrow blasts are eligible if they have:
- A karyotypic abnormality characteristic of de novo AML (t(8;21)(q22;q22), inv(16)(p13q22) or t(16;16)(p13;q22) or 11q23 abnormalities
- The unequivocal presence of megakaryoblasts, or
- Biopsy proven isolated myeloid sarcoma (myeloblastoma; chloroma, including leukemia cutis)
- Patients with any performance status are eligible for enrollment
- Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy; patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
Exclusion Criteria
- Patients with any of the following constitutional conditions are not eligible:
- Fanconi anemia
- Shwachman syndrome
- Any other known bone marrow failure syndrome
- Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21 Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
- Patients with any of the following oncologic diagnoses are not eligible:
- Any concurrent malignancy
- Juvenile myelomonocytic leukemia (JMML)
- Philadelphia chromosome positive AML
- Biphenotypic or bilineal acute leukemia
- Acute promyelocytic leukemia
- Acute myeloid leukemia arising from myelodysplasia
- Therapy-related myeloid neoplasms Note: enrollment may occur pending results of clinically indicated studies to exclude these conditions
- Pregnancy and breast feeding
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
Data sourced from ClinicalTrials.gov (NCT01371981). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.