Myelodysplastic Syndromes Clinical Trial
Official title:
A Pilot Study of IFN-γ to Treat Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) That Has Relapsed After Allogeneic Hematopoietic Stem Cell Transplantation
This study proposes a safe dosing regimen IFN-γ that is sufficient to stimulate IFN-γ receptors on malignant blasts in patients who developed relapsed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after alloSCT with no active or history of III-IV acute graft-versus-host disease (GVHD). It is hypothesized that IFN-γ will promote graft-vs-leukemia (GVL) in patients with AML/MDS that has relapsed after alloSCT.
Allogeneic hematopoietic stem cell transplantation (alloSCT) can cure patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, relapsed AML/MDS is the most significant single cause of treatment failure, and the majority of relapsed patients ultimately succumb. Alloreactive T cells in the donor graft can kill residual leukemia cells, mediating the graft-vs-leukemia (GVL) effect. Consistent with this, recipients of T cell-depleted grafts have higher rates of relapse. GVL is more potent against chronic leukemias than acute myeloblastic diseases, and the higher incidence of relapse in patients with AML/MDS reflects a failure in GVL. The central goal of this pilot trial will be to explore whether IFN-γ in this setting is safe and whether it has the desired biological activities on malignant blasts in vivo. IFN-γ will be tested in relapsed patients as monotherapy and in conjunction with donor leukocyte infusions (DLI). The clinical and biological information from this study is essential to design a phase II trial with a therapeutic endpoint. Treatment will be initiated at 100mcg (almost equal to the dose of 50 mcg/m2 for an adult) three times a week, with the potential to deescalate the frequency of injection for unacceptable toxicity. To explore whether this dosing regimen is sufficient to activate myeloblasts, pre- and post-treatment bone marrow specimens will be harvested to analyze for IFN-γ action (upregulation of HLA class I; HLA class II, ICAM-1 and phosphorylation of STAT1). The primary safety concern is the development of GVHD, which is routinely monitored for all alloSCT patients. ;
| 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 | |
| Terminated |
NCT04313881 -
Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS)
|
Phase 3 | |
| Recruiting |
NCT05088356 -
Reduced Intensity Allogeneic HCT in Advanced Hematologic Malignancies w/T-Cell Depleted Graft
|
Phase 1 | |
| Recruiting |
NCT04003220 -
Idiopathic Chronic Thrombocytopenia of Undetermined Significance : Pathogenesis and Biomarker
|
||
| Completed |
NCT02916979 -
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
|
Phase 1 | |
| Active, not recruiting |
NCT03755414 -
Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation
|
Phase 1 | |
| Completed |
NCT00003270 -
Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
|
Phase 2 | |
| Recruiting |
NCT04904588 -
HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide
|
Phase 2 | |
| Terminated |
NCT04866056 -
Jaktinib and Azacitidine In Treating Patients With MDS With MF or MDS/MPN With MF.
|
Phase 1/Phase 2 | |
| Recruiting |
NCT04701229 -
Haploinsufficiency of the RBM22 and SLU7 Genes in Del(5q) Myelodysplastic Syndromes
|
||
| Suspended |
NCT04485065 -
Safety and Efficacy of IBI188 With Azacitidine in Subjects With Newly Diagnosed Higher Risk MDS
|
Phase 1 | |
| Recruiting |
NCT04174547 -
An European Platform for Translational Research in Myelodysplastic Syndromes
|
||
| 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 | |
| Completed |
NCT02508870 -
A Study of Atezolizumab Administered Alone or in Combination With Azacitidine in Participants With Myelodysplastic Syndromes
|
Phase 1 | |
| Completed |
NCT04543305 -
A Study of PRT1419 in Patients With Relapsed/Refractory Hematologic Malignancies
|
Phase 1 | |
| Recruiting |
NCT05384691 -
Efficacy of Luspatercept in ESA-naive LR-MDS Patients With or Without Ring Sideroblasts Who do Not Require Transfusions
|
Phase 2 | |
| Recruiting |
NCT05365035 -
A Phase II Study of Cladribine and Low Dose Cytarabine in Combination With Venetoclax, Alternating With Azacitidine and Venetoclax, in Patients With Higher-risk Myeloproliferative Chronic Myelomonocytic Leukemia or Higher-risk Myelodysplastic Syndromes With Excess Blasts
|
Phase 2 | |
| Recruiting |
NCT06008405 -
Clinical Trial Evaluating the Safety of the TQB2928 Injection Combination Therapy
|
Phase 1 | |
| Not yet recruiting |
NCT05969821 -
Clonal Hematopoiesis of Immunological Significance
|
||
| Withdrawn |
NCT05170828 -
Cryopreserved MMUD BM With PTCy for Hematologic Malignancies
|
Phase 1 |