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Sirolimus

Patients enrolled and treated with PTCy/sirolimus plus VIC-1911

25 mg, 50 mg, or 75 mg administered twice a day from day 5 post HCT to day 45, and the dose escalation will stop once we identify the lowest biologically active and safe dose of VIC.

VIC- 1911

Cancer Center Clinical Trials Office

Sherman Holtan, MD

This is a single-arm, phase I/II, study of PTCy/sirolimus plus VIC-1911 to prevent GVHD and relapse after Allogeneic Hematopoietic Cell Transplantation (alloHCT).

Determination of the optimal dose during the Phase I trial is based on Dose Limiting Toxicity for safety and reduction of CD4+, pH3ser10+ T cells (phosphorylated histone 3 serine 10 is a biomarker of Aurora kinase A activity) for efficacy. Phase II will be powered to improve grade III-IV acute graft-versus-host disease and relapse after alloHCT, compared to historical estimates at the University of Minnesota.

Patients will receive myeloablative conditioning (MAC) with total body irradiation (TBI) followed by infusion of HLA-matched related or unrelated peripheral blood stem cells (PBSC) on day 0. Cyclophosphamide will be administered on days +3 and +4. Sirolimus targeting 8-12ng/ml will begin on day +5 until day +365. VIC-1911 will be administered as 25 mg, 50 mg, or 75 mg orally BID from day +5 to day +45 according to the rules of our phase I study. The lowest biologically active and safe dose of VIC-1911 will be identified as the recommended phase II dose.

PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation

The optimal dose will be identified using the EffTox design. The proportion of patients with an average CD4+, pH3ser10+ T cell of \<54%. The minimum desired biologic efficacy is 65% of patients by day 21 (+/- 3 days) with \<30% of patients experiencing a DLT.

Assessment to determine if patient has relapse

Determine the frequency of CD4+, pS6+ \[marker of mTOR activity\] and CD4+, pSTAT5+ \[marker of IL-2 activity\] cells

GRFS defined as grade III-IV acute GVHD, chronic GVHD requiring immunosuppression, relapse, or death by 1 year

Comparison hospitalization days with another trial's data (MT2015-29)

Use quality of life questionnaire to measure patients' quality of life.

Masonic Cancer Center, University of Minnesota

Recurrence

Hematologic Neoplasms

Graft vs Host Disease

Disease Attributes

Homologous Wasting Disease

Myeloablative hematopoietic stem cell transplantation from many kinds of donors, including matched related donor, matched unrelated donor, haploidentical related donor.

Myeloablative Hematopoietic Stem Cell Transplantation

Graft-versus-Host Disease (GVHD) and relapse, which is mainly due to lack of Graft-versus-Leukemia (GVL), are the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells expanded from mature T cells in the graft play a dominant role in development of GVHD and GVL early after allo-HSCT. Recent applications of high-throughput sequencing (HTS) to the T cells repertoire open a new avenue for us to look deeply into how these T cells dynamically adjust in the context of the recipient's environment.

The main goal of this research study is to set up a mathematical model based on T cell receptor (TCR) sequencing to enable prediction for the key immunologic outcomes early post-transplantation. This study will deepen the understanding of the molecular mechanisms driving the most deadly post-transplantation complications, and serve as convincing evidence upon which to choose a better donor and a more proper transplantation approach.

This observational trial will perform HTS for TCR β-chain complementarity determining region 3 (CDR3) repertoires of grafts and peripheral blood samples from recipients post-transplantation and analyze the relationship between dynamics of TCR CDR3 repertoires and clinical outcomes early post-transplantation, especially including GVHD and relapse. The investigators want to know how the antigen environment in recipients drives dynamics of mature T cells from grafts in order to use the new discovered rules to better predict and treat the disease process.

Characteristics and Dynamics of TCR Repertoire in Patients With Hematological Malignancies After Allo-HSCT

Characteristics and Dynamics of TCR Repertoire in Peripheral Blood of Patients With Hematological Malignancies After Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation

To identify the mechanisms specific for TCR repertoire dynamics and rearrangement characteristics.

Characterize the main TCR β-chain CDR3 sequences dynamic change responsible for acute GVHD, chronic GVHD and defects in protective immunity in patients undergoing HSCT.

Characterize the TCR β-chain CDR3 repertoire dynamic change responsible for acute GVHD, chronic GVHD and defects in protective immunity in patients undergoing HSCT.

Hangzhou ImmuQuad Biotechnologies, LLC

Affiliated Hospital to Academy of Military Medical Sciences

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Chronic Myeloid Leukemia

Hodgkin Lymphoma

Antirheumatic Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Fludarabine 30mg/m2 IV days -6 to -2 Cyclophosphamide 14.5 mg/kg IV days -6 and -5 Total body irradiation 2Gy day -1 Stem cell transplant: day 0 Cyclophosphamide 50mg/kg days +3 \& +4

Total body irradiation 12Gy in 8 fractions days -9 to -6 Donor lymphocyte infusion day -6 Cyclophosphamide 60mg/kg IV days -3 \& -2 Stem cell transplant day 0

Reduced intensity haplodentical stem cell transplant

Myeloablative haploidentical stem cell transplant

Dr Kavita Raj

This trial investigates stem cell transplants from partially mismatched donors in patients with blood and bone marrow cancers. The trial will test two kinds of transplants - a full intensity transplant using a high dose of radiotherapy and chemotherapy, and a reduced intensity transplant with lower doses of chemotherapy and radiotherapy. Patients will be entered for the treatment pathway that is most appropriate for their level of health and fitness

Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers

A UK Multicentre Study of Haploidentical Stem Cell Transplantation in Patients With Haematological Malignancies

Bloodwise

University College, London

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation	NCT05120570	Acute Leukemia Myelodysplastic... Myeloproliferat... Lymphoma	VIC- 1911	18 Years -	Masonic Cancer Center, University of Minnesota
Characteristics and Dynamics of TCR Repertoire in Patients With Hematological Malignancies After Allo-HSCT	NCT03575767	Hematologic Neo... Hematopoietic S... Graft Vs Host D... Recurrence	Myeloablative H...	12 Years - 55 Years	Affiliated Hospital to Academy of Military Medical Sciences
Trial of Haploidentical Stem Cell Transplantation for Haematological Cancers	NCT01597219	Hodgkin's Lymph... Non-Hodgkin's L... Acute Myeloid L... Acute Lymphobla... Myelodysplastic... Chronic Myeloid... Chronic Lymphoc... Acquired Bone M... Other Haematolo...	Reduced intensi... Myeloablative h...	16 Years - 70 Years	University College, London
PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation	NCT05120570	Acute Leukemia Myelodysplastic... Myeloproliferat... Lymphoma	VIC- 1911	18 Years -	Masonic Cancer Center, University of Minnesota
PTCy + Sirolimus/VIC-1911 as GVHD Prophylaxis in Myeloablative PBSC Transplantation	NCT05120570	Acute Leukemia Myelodysplastic... Myeloproliferat... Lymphoma	VIC- 1911	18 Years -	Masonic Cancer Center, University of Minnesota

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