Phase II Study of 5-azacytidine Maintenance After Transplant for AML or MDS (UPCI 13-165)
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|ClinicalTrials.gov Identifier: NCT02204020|
Recruitment Status : Withdrawn (Lack of interest with investigators - no subjects enrolled)
First Posted : July 30, 2014
Last Update Posted : March 30, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS)||Drug: 5-azacytidine (5-aza) maintenance therapy after transplant||Phase 2|
Phase II study of 5-aza maintenance after allogeneic Hematopoietic Cell Transplantation (HCT) for high-risk Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS). Early studies indicate 5-aza is a hypomethylating agent that has shown immune modulating properties that may enhance the graft-versus-leukemia (GVL) effect, including upregulation of tumor-associated antigen and costimulatory molecule expression. 5-aza also has properties that suggest protection against graft-versus-host disease (GVHD). The primary objective is to evaluate relapse rate at one year. Secondary objectives will include the incidence of both acute and chronic GVHD as well as relapse-free survival, overall survival and toxicity. Correlatives will be performed to evaluate the effect of 5-aza maintenance on the immune system.
Subjects must be transplant candidates with MDS or high risk characteristics of AML. Subjects are consented, screened, then transplanted. Those showing complete response and no active GVHD after transplant can proceed to maintenance with 5-aza. Bone marrow biopsies are performed for response assessment after transplant as well as every three cycles (1 cycle=28 days) while on treatment. Dosing starts at 32mg/m2 and can be increased every 2 cycles without a serious adverse event (SAE), or reduced per toxicity for up to 12 cycles.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of 5-azacytidine Maintenance After Allogeneic Hematopoietic Cell Transplantation for High-risk Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)|
|Actual Study Start Date :||April 2015|
|Actual Primary Completion Date :||April 2015|
|Actual Study Completion Date :||May 4, 2016|
5-aza SC or IV 32mg/m2 - 75mg/m2 (based on dose escalation)
Drug: 5-azacytidine (5-aza) maintenance therapy after transplant
The planned initial dose of 5-aza is 32mg/m2 (Level 0) administered either subcutaneously or intravenously for days 1 through 5 of a 28-day cycle, which will be initiated between day+30 and day+100 after HCT. Patients who tolerate this dose based on hematologic parameters and with no SAEs for two consecutive cycles will be eligible for a dose escalation to 50mg/m2 (Level +1). Patients who tolerate this dose based on the same criteria as above for two consecutive cycles will be eligible for a dose escalation to 75mg/m² (Level +2). Patients will continue at dose Level +2 for the remainder of the study provided there are no toxicities that require dose reduction. Patients requiring a dose reduction are not eligible for re-escalation.
Other Name: 5-aza
- Relapse rate at 1 year [ Time Frame: 3 years ]Study will evaluate the relapse rate associated with 5-azacytidine (5-aza) as maintenance therapy after HCT in patients with high-risk AML or MDS.
- Safety of Toxicity Requiring Treatment Discontinuation (TRTD) [ Time Frame: 3 years ]
- Overall survival [ Time Frame: 3 years ]
- Incidence of acute GVHD [ Time Frame: 3 years ]
- Percentage of Toxicity Requiring Treatment Discontinuation (TRTD) [ Time Frame: 3 years ]
- relapse-free survival [ Time Frame: 3 years ]
- Incidence of chronic GVHD [ Time Frame: 3 years ]
- Effect on the immune system [ Time Frame: 3 years ]Study will evaluate the effect of 5-aza maintenance on the immune system using T-cell phenotype subsets and receptor expression, cytokine levels including tumor necrosis factor alpha (TNFα) and Interferon-y (IFNγ) (proinflammatory), and interleukin 7 (IL-7) and interleukin 15 (IL-15) (homeostatic) and association of correlative measures with relapse and incidence of GVHD.
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): NCT02204020
|United States, Pennsylvania|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15232|
|Principal Investigator:||Annie Im, MD||University of Pittsburgh Medical Center|