Vorinostat Dose-escalation After Allogeneic Hematopoietic Cell Transplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03843528|
Recruitment Status : Recruiting
First Posted : February 18, 2019
Last Update Posted : July 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia Myelodysplastic Syndromes Mixed Phenotype Acute Leukemia Juvenile Myelomonocytic Leukemia||Drug: Vorinostat Drug: Azacitidine Injection||Phase 1|
Children and adolescents ages 1 to 21 years of age who are undergoing allogeneic hematopoietic cell transplantation for a myeloid malignancy (AML, MDS, JMML, MPAL) will be eligible. There are no restrictions on donor type, conditioning, stem cell source, of GVHD prophylaxis approach.
All participants will be treated on a single arm, and will initially receive 2 cycles of standard post-transplant azacitidine at a dose of 32mg/m2/dose IV/subcutnaeous for 5 days, in 28 day cycles. This is considered standard of care.
After tolerance of 2 cycles of azacitidine has been established, patients will be assigned to receive vorinostat orally at different dose levels, depending on the stage of the study. The dose level assignments will be conducted on a standard 3+3 design, whereby dose-escalation is peformed if previous patients tolerated the dose without dose-limiting toxicities, and dose-reduction is performed if dose-limiting toxicities are seen. The starting dose will be 100mg/m2/dose on days 1-7 and 15-21 of each 28 day cycles. This will be in addition to receiving azacitidine at the fixed dose above. In order to start each cycle, participants will be required to meet specific clinical parameters to ensure safety.
The dose of vorinostat between patients will be escalated or de-escalated until criteria for finding the maximum tolerated dose (MTD) is reached, and this will complete the study. Participants will continue to receive the prescribed dose of vorinostat for up to 7 cycles (9 total cycles of azacitidine).
Participants are followed for dose-limiting toxicities primarily during the first two course of combined therapy (cycles 3 and 4), but are continued to be tracked until the completion of all potential combined treatment (1 year or 7 combined cycles, whichever is earlier).
1. To evaluate the maximum tolerated dose (MTD) of vorinostat used in combination with low-dose azacitidine after allogeneic hematopoietic cell transplantation (alloHCT) for childhood myeloid malignancies.
- To describe the dose-limiting toxicities (DLT) of the vorinostat used in combination with low-dose azacitidine.
- To describe rates of relapse, transplant related mortality, graft-versus-host disease, and overall survival.
- To describe the effect of epigenetic modification on lymphocyte reconstitution in the post-alloHCT setting.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||3+3 dose-escalation study|
|Masking:||None (Open Label)|
|Official Title:||Epigenetic Modification for Relapse Prevention: a Dose-finding Study of Vorinostat Used in Combination With Low-dose Azacitidine in Children Undergoing Allogeneic Hematopoietic Cell Transplantation for Myeloid Malignancies|
|Actual Study Start Date :||May 1, 2019|
|Estimated Primary Completion Date :||May 1, 2021|
|Estimated Study Completion Date :||December 31, 2021|
Experimental: Combined therapy
Patients will be enrolled in blocks of 3, with vorinostat dose-escalation according to 3+3 study design.
Low-dose azacitidine will be administered in a fixed dose to all patients, for days 1-5 of each 28 day cycle.
Vorinostat will be administered concurrent with low-dose azacitidine post-transplant, on days 1-7 and 15-21 of 28 day cycles. This is an oral medication.
Drug: Azacitidine Injection
Azacitidine will be administered on days 1-5 of each 28 day cycle, either by IV or subcutaneous injection. The dose of azacitidine will be fixed, with no dose-escalation.
- Maximum tolerated dose (MTD) [ Time Frame: 4 months ]The primary outcome of this study is to determine the MTD of vorinostat in combination with low-dose azacitidine, using dose-escalation methodology. This is based on toxicities developed by participants enrolled on the study.
- Dose-limiting toxicities [ Time Frame: 4 months ]Rates of side effects from vorinostat will be recorded and described.
- GVHD [ Time Frame: 1 year ]Incidence of GVHD will be recorded and described.
- Relapse [ Time Frame: 1 year ]Incidence of relapse will be recorded and described
- Survival [ Time Frame: 1 year ]Duration of survival will be recorded and described
- Immune recovery [ Time Frame: 1 year ]Immune profile will be measured monthly for the first year post-transplant.
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): NCT03843528
|Contact: Benjamin Oshrine, MDemail@example.com|
|United States, Florida|
|Johns Hopkins All Children's Hospital||Recruiting|
|Saint Petersburg, Florida, United States, 33701|
|Contact: Benjamin Oshrine, MD firstname.lastname@example.org|
|Principal Investigator:||Benjamin Oshrine, MD||Johns Hopkins All Children's Hospital|