View clinical trials related to Hematologic Neoplasms.
Filter by:Allogeneic stem cell transplantation (allo-SCT) is a potent treatment, and sometimes the only curative treatment for aggressive hematological malignancies. The therapeutic efficacy is attributed to the graft-versus-tumor (GVT) response, during which donor-derived CD8+ T cells become activated by recipient minor histocompatibility antigens (MiHA) presented on dendritic cells (DC). Consequently, these alloreactive donor T cells clonally expand, acquire effector functions and kill MiHA-positive malignant cells. However, in a substantial number of patients persistence and recurrence of malignant disease is observed, indicating that insufficient GVT immunity is induced. This is reflected by our observation that not all patients develop a productive CD8+ T cell response towards MiHA mismatched between the recipient and donor. We found that the PD-1/PD-L1 co-inhibitory pathway is involved in dampening MiHA-specific CD8+ T cell expansion and function post-transplantation. Therefore, a promising strategy to induce or boost GVT immune responses is pre-emptive or therapeutic vaccination with ex vivo-generated donor DCs loaded with MiHA that are exclusively expressed by recipient hematopoietic cells and their malignant counterparts. In contrast to pre-emptive donor lymphocyte infusion (DLI) with polyclonal donor T cells, this MiHA-DC vaccination approach has less risk of inducing graft-versus-host disease (GVHD) and the potency to induce more efficient GVT-associated T cell immunity. In addition, the potency of this DC vaccine will be further enhanced by interference with the PD-1/PD-L1 co-inhibitory pathway, using siRNA mediated PD-L1/PD-L2 silencing.
The administration of high-dose chemotherapy followed by the infusion of blood or bone marrow stem cells (stem cell transplantation) from a matched donor has become standard treatment for patients with high-risk or relapsed hematological cancers. Currently, donors are found for approximately 80% of people who require such treatment, although the chance of finding a donor is much lower in some ethnic communities. In the current study the investigators will offer patients requiring transplantation, but for whom well matched donors cannot be identified either from within the family or on the donor registry, a transplant from a half-matched (haploidentical) family member. A myeloablative conditioning regimen and un-manipulated peripheral blood stem cells will be used. Post-transplant cyclophosphamide, tacrolimus and mycophenolate mofetil will be used to prevent graft versus host disease (GVHD). The primary outcome measure will be 6 month survival free from graft failure, relapse and grade 3-4 acute GVHD. Other outcomes of interest will include the frequency of Cytomegalovirus (CMV) or Epstein-Barr Virus (EBV) requiring treatment, overall survival and progression-free survival.
The purpose of this study is to determine whether a repeat dose administration of ATIR101 is safe and effective when infused in patients with a hematologic malignancy following a T-cell depleted stem cell graft from a related haploidentical donor. All patients are planned to receive two ATIR101 doses of 2×10E6 viable T-cells/kg, unless the second dose is reduced or halted for safety reasons.
The goal of this study is to determine whether post-transplant consolidation with azacitidine combined with donor lymphocyte infusion (DLI) is a safe and effective approach for the prevention of relapse in pediatric and young adult patients with hematologic malignancies who have undergone hematopoietic stem cell transplantation (HSCT).
CC-90002-ST -001 is an open-label, Phase 1, dose escalation clinical study in subjects with advanced, refractory solid and hematologic cancers.
This research study is evaluating if co-management by a geriatrician embedded in the oncology clinic can improve outcomes for frail older adults with blood cancers. A rigorous pre-entry frailty assessment by a trained research assistant will be followed by randomization to geriatrician co-management versus usual care for patients found to be frail or pre-frail.
This is a multicenter, open label, Phase 1 dose-escalation study of BBI608 administered to patients with relapsed, refractory hematologic malignancies, including multiple myeloma, lymphoma, and others.
This Phase 1 clinical study is designed to examine the safety and feasibility of using anti-CD3/CD28 activated marrow infiltrating lymphocytes (MILs) as treatment of relapse after allogeneic hematopoietic cell transplantation (alloHCT) for patients with hematologic malignancies with bone marrow involvement of their relapsed disease. These MILs will be derived from the bone marrow of the relapsed patient who had previously received post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GVHD) prophylaxis (PTCy-MILs). A bone marrow aspiration will be performed on the patient to collect ~200ml of marrow for ex vivo expansion. During this expansion process, T cells will be activated and expanded by co-stimulation with anti-CD3/anti-CD28 monoclonal antibodies covalently attached to super-paramagnetic microbeads. Patients will be treated with salvage therapy while this ex vivo expansion is ongoing. After the simultaneous salvage therapy and ex vivo expansion, the activated PTCy-MILs will be reinfused. Patients will be monitored with the primary objective being the feasibility of expanding to targeted dose levels activated PTCy-MILs that do not cause grade III-IV acute GVHD within the first 90 days after PTCy-MIL infusion.
The primary goal of this study is to evaluate an alternative myeloablative, but reduced toxicity conditioning regimen in children, to describe the safety and efficacy of intravenous (i.v.) Treosulfan administered as part of a standardised Fludarabine-containing conditioning and to contribute to the current pharmacokinetic model to be able to finally give age (or body surface area) dependent dose recommendations. The treatment regimens given in the protocol MC-FludT.17/M are based on sufficient clinical safety and efficacy data. Considering the vital indication for allogeneic haematopoietic stem cell transplantation of the selected patient population, the risk-benefit assessment is therefore reasonably in favour of the study conduct.
The purpose of this study is to determine the safety and to establish the recommended phase 2 dose (RP2D) for the combination of ibrutinib and nivolumab in participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), follicular cell lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Once the dose is optimized, the combination will be assessed for Pharmacokinetics, Pharmacodynamics, and preliminary efficacy, further safety in participants with CLL/SLL, FL or DLBCL and in participants with Richter syndrome.