Acute Myeloid Leukemia Clinical Trial
Official title:
A Phase II Study of Bortezomib and Vorinostat in Patients With Refractory or Relapsed MLL Rearranged Hematologic Malignancies
This study will test the safety and effectiveness of adding bortezomib and vorinostat to
other chemotherapy drugs commonly used to treat relapsed or refractory leukemia. Both drugs
have been approved by the Food and Drug Administration (FDA) to treat other cancers in
adults, but they have not yet been approved tor treatment younger patients with leukemia.
PRIMARY OBJECTIVE
- To estimate the overall response rate of patients with MLL rearranged (MLLr) hematologic
malignancies receiving bortezomib and vorinostat in combination with a chemotherapy
backbone.
SECONDARY OBJECTIVES
- Estimate event-free and overall-survival.
- Describe toxicities experienced by participants during treatment.
OTHER PRESPECIFIED OBJECTIVES
- To identify all genomic lesions by comprehensive whole genome, exome and transcriptome
sequencing on all patients.
- To compare minimal residual disease (MRD) results by three modalities: flow cytometry,
polymerase chain reaction (PCR) and deep sequencing.
All participants will undergo diagnostic lumbar puncture and intrathecal (IT) chemotherapy
[Cytarabine, methotrexate, hydrocortisone (ITMHA)] prior to cycle 1. Throughout all phases of
therapy, dexrazoxane will be given as supportive care for all participants prior to receiving
mitoxantrone or doxorubicin.
STRATUM 1: MYELOID MALIGNANCIES:
Induction:
- Cytarabine, Days 1-5
- Bortezomib, Days 1, 4, 8, 11, 15, 18
- Vorinostat, Days 1-4, 8-11, 15-18
- ITMHA.for those with CNS1, Day 1
- ITMHA for those with CNS 2/3, Days 1, 4, 8, 11*, 15*, 18* and 22* (* Twice weekly until
two negative CSF; CNS3 patients must receive at least 6 doses)
- Participants with cumulative anthracycline <460 mg/m2 also receive Mitoxantrone on Day 1
- Responders may receive up to 6 courses. ITMHA will be limited to day 1 for subsequent
courses
Maintenance (bridge) therapy (1 cycle before stem cell transplant if needed)::
- Bortezomib, Days 1, 4, 8, 11, 15, 18
- Vorinostat, Days 1-4, 8-11, 15-18
- ITMHA, Day 1
STRATUM 2: Acute Lymphoid Leukemia (ALL) and Mixed Lineage Malignancies (MLL):
Induction:
- Mitoxantrone, Day 1
- PEG-L-Asparaginase (or Erwinia L-asparaginase), Day 3
- Dexamethasone, Days 1-4, 8-11, 15-18
- Bortezomib, Days 1, 4, 8, 11, 15, 18
- Vorinostat, Days 1-4, 8-11, 15-18
- ITMHA for those with CNS1, Days 1, 8, 15, and 22
- ITMHA for those with CNS2/3, Days 1, 4, 8, 11, 15, and 22
- Participants with >460 mg/m2 cumulative anthracyclines will not receive mitoxantrone
Consolidation:
- Methotrexate, Days 1 and 15
- Bortezomib, Days 8, 11, 22, 25
- Vorinostat, Days 8-11, and 22-25
- ITMHA, Days 1 and 15
Interim Maintenance:
- Mercaptopurine, Days 1-42
- Doxorubicin, Days 1 and 29
- PEG-L-asparaginase (or Erwinia L-asparaginase), Days 1, 15, and 29
- Dexamethasone, Days 8-11, 22-25, and 36-39
- Bortezomib Days 8,11,22,25,36,39
- Vorinostat, Days 8-11, 22-25, and 36-39
- ITMHA, Day 1
Reinduction:
- Mitoxantrone, Day 1
- PEG-L-asparaginase (or Erwinia L-asparaginase), Day 3
- Dexamethasone, Days 1-4, 8-11, 15-18
- Bortezomib Days 1, 4, 8, 11, 15, 18
- Vorinostat Days 1-4, 8-11, 15-18
- IT MHA Day 1
Maintenance (12 cycles):
- Mercaptopurine, Days 1-28
- Methotrexate, Days 8, 15, and 22
- Dexamethasone, Days 1-4
- Bortezomib, Days 1 and 4
- Vorinostat, Days 1-4
- ITMHA, Day 1
Bridge Therapy (1 cycle before stem cell transplant if needed):
- Bortezomib, Days 1, 4, 8, 11, 15, 18
- Vorinostat, Days 1-4, 8-11, 15-18
- Dexamethasone, Days 1-4, 8-11, 15-18
- ITMHA, Day 1
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Recruiting |
NCT04460235 -
Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma
|
Phase 4 | |
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Completed |
NCT03678493 -
A Study of FMT in Patients With AML Allo HSCT in Recipients
|
Phase 2 | |
Recruiting |
NCT05424562 -
A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
|
||
Terminated |
NCT03224819 -
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
|
Early Phase 1 | |
Completed |
NCT03197714 -
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
|
Phase 1 | |
Active, not recruiting |
NCT04070768 -
Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113
|
Phase 1 | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Active, not recruiting |
NCT04107727 -
Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)
|
Phase 2 | |
Recruiting |
NCT04385290 -
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
|
Phase 1/Phase 2 | |
Recruiting |
NCT04920500 -
Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients
|
N/A | |
Recruiting |
NCT03897127 -
Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
|
Phase 3 | |
Active, not recruiting |
NCT04021368 -
RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT03665480 -
The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML
|
Phase 2/Phase 3 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Recruiting |
NCT04069208 -
IA14 Induction in Young Acute Myeloid Leukemia
|
Phase 2 | |
Recruiting |
NCT05744739 -
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Phase 1 | |
Recruiting |
NCT04969601 -
Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
|
Phase 1/Phase 2 |