Increased Foxp3Helios Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells.

Regulatory T (Treg) cells play a central role in immune tolerance and prevention of aberrant immune responses. Several studies have suggested that the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) can be ameliorated by increasing Tregs. We have developed an approach of in vivo expansion of Tregs with RGI-2001, a novel liposomal formulation of a synthetic derivative of alpha-galactosylceramide, a naturally occurring ligand that binds to CD1 and activates and expands invariant natural killer cells.

Characterization of CD33/CD3 Tetravalent Bispecific Tandem Diabodies (TandAbs) for the Treatment of Acute Myeloid Leukemia.

Purpose: Randomized studies with gemtuzumab ozogamicin have validated CD33 as a target for antigen-specific immunotherapy of acute myelogenous leukemia (AML). Here, we investigated the potential of CD33/CD3-directed tandem diabodies (TandAbs) as novel treatment approach for AML. These tetravalent bispecific antibodies provide two binding sites for each antigen to maintain the avidity of a bivalent antibody and have a molecular weight exceeding the renal clearance threshold, thus offering a longer half-life compared to smaller antibody constructs.

ENGAGE- 501: phase II study of entinostat (SNDX-275) in relapsed and refractory Hodgkin lymphoma.

Classical Hodgkin lymphoma treatment is evolving rapidly with high response rates from antibody-drug conjugates targeting CD30 and immune checkpoint antibodies. However, most patients do not achieve a complete response, therefore development of novel therapies is warranted to improve patient outcomes. In this phase II study, patients with relapsed or refractory Hodgkin lymphoma were treated with entinostat, an isoform selective histone deacetylase inhibitor.

Modeling absolute lymphocyte counts after treatment of chronic lymphocytic leukemia with ibrutinib.

The objective in this study was to characterize the pattern of the treatment-related lymphocytosis curve in chronic lymphocytic leukemia (CLL) patients treated with ibrutinib, and assess the relationship between the baseline factors and absolute lymphocyte counts (ALC). The PCYC-1102-CA study was a five-arm phase Ib/II open-label, nonrandomized, multicenter study in CLL/SLL. The arms and accruals were 420 and 840 mg/day treatment-naive elderly CLL/SLL (N = 27 and N = 4, respectively), 420 and 840 mg/day relapsed/refractory CLL/SLL (N = 27 and N = 34, respectively), and 420 mg/day high-risk CLL/SLL (N = 24).

Active idiotypic vaccination versus control immunotherapy for follicular lymphoma.

Purpose: Idiotypes (Ids), the unique portions of tumor immunoglobulins, can serve as targets for passive and active immunotherapies for lymphoma. We performed a multicenter, randomized trial comparing a specific vaccine (MyVax), comprising Id chemically coupled to keyhole limpet hemocyanin (KLH) plus granulocyte macrophage colony-stimulating factor (GM-CSF) to a control immunotherapy with KLH plus GM-CSF.

Patients And Methods: Patients with previously untreated advanced-stage follicular lymphoma (FL) received eight cycles of chemotherapy with cyclophosphamide, vincristine, and prednisone.

Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma.

Background: Bruton's tyrosine kinase (BTK) is a mediator of the B-cell-receptor signaling pathway implicated in the pathogenesis of B-cell cancers. In a phase 1 study, ibrutinib, a BTK inhibitor, showed antitumor activity in several types of non-Hodgkin's lymphoma, including mantle-cell lymphoma.

Methods: In this phase 2 study, we investigated oral ibrutinib, at a daily dose of 560 mg, in 111 patients with relapsed or refractory mantle-cell lymphoma.

Phase Ib dose-escalation study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma.

Purpose: Carfilzomib, a selective proteasome inhibitor, has shown safety and efficacy in relapsed and/or refractory multiple myeloma. This phase I study in patients with relapsed or progressive multiple myeloma assessed the safety and tolerability of escalating doses of carfilzomib in combination with lenalidomide and low-dose dexamethasone (CRd) to identify the dose for a phase II expansion study.

Experimental Design: Patients with multiple myeloma who relapsed after 1 to 3 prior regimens enrolled into dose-escalation cohorts.

An open-label single-arm pilot phase II study (PX-171-003-A0) of low-dose, single-agent carfilzomib in patients with relapsed and refractory multiple myeloma.

Unlabelled: An open-label single-arm multicenter pilot phase II study of the next-generation selective proteasome inhibitor carfilzomib was conducted in 46 patients with relapsed and refractory multiple myeloma (MM) after ≥ 2 previous therapies. The best overall response rate (ORR) was 16.7%, with a median duration of response of 7.

An open-label, single-arm, phase 2 study of single-agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib.

Carfilzomib is a next-generation proteasome inhibitor that selectively and irreversibly binds to its target. In clinical studies, carfilzomib has shown efficacy in patients with relapsed and/or refractory multiple myeloma (MM) and has demonstrated a tolerable safety profile. In this phase 2, open-label, multicentre clinical trial, 35 patients with relapsed and/or refractory MM following 1-3 prior therapies, including at least one bortezomib-based regimen, received carfilzomib 20 mg/m(2) in a twice-weekly, consecutive-day dosing schedule for ≤12 monthly cycles.

A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma.

Carfilzomib is a next-generation, selective proteasome inhibitor being evaluated for the treatment of relapsed and refractory multiple myeloma. In this open-label, single-arm phase 2 study (PX-171-003-A1), patients received single-agent carfilzomib 20 mg/m(2) intravenously twice weekly for 3 of 4 weeks in cycle 1, then 27 mg/m(2) for ≤ 12 cycles. The primary endpoint was overall response rate (≥ partial response).

A phase I single-agent study of twice-weekly consecutive-day dosing of the proteasome inhibitor carfilzomib in patients with relapsed or refractory multiple myeloma or lymphoma.

Purpose: Carfilzomib is a next-generation, selective, proteasome inhibitor with clinical activity in relapsed and/or refractory multiple myeloma. The objectives of this phase I study were to establish the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of escalating doses of carfilzomib in patients with relapsed or refractory hematologic malignancies.

Experimental Design: Carfilzomib (doses ranging from 1.

An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma.

Carfilzomib is a selective proteasome inhibitor that binds irreversibly to its target. In phase 1 studies, carfilzomib elicited promising responses and an acceptable toxicity profile in patients with relapsed and/or refractory multiple myeloma (R/R MM). In the present phase 2, multicenter, open-label study, 129 bortezomib-naive patients with R/R MM (median of 2 prior therapies) were separated into Cohort 1, scheduled to receive intravenous carfilzomib 20 mg/m(2) for all treatment cycles, and Cohort 2, scheduled to receive 20 mg/m(2) for cycle 1 and then 27 mg/m(2) for all subsequent cycles.

Phase 1 experience with an anti-glycotope monoclonal antibody, RAV12, in recurrent adenocarcinoma.

Purpose: RAV12 is a high affinity, internalizing, chimeric IgG1 monoclonal antibody that binds RAAG12, a novel primate-restricted N-linked carbohydrate epitope present on multiple cell surface proteins. RAAG12 is highly expressed on many adenocarcinomas, particularly those of gastrointestinal origin. A phase 1 dose-escalation safety and pharmacokinetics trial was conducted in patients with metastatic or recurrent adenocarcinomas.

A phase 1 dose escalation study of the safety and pharmacokinetics of the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic malignancies.

Purpose: Carfilzomib (formerly PR-171) is a novel proteasome inhibitor of the epoxyketone class that is selective and structurally distinct from bortezomib. Proteasome inhibition by carfilzomib is mechanistically irreversible. Consequently, proteasome inhibition is more sustained with carfilzomib than with bortezomib.

Combination of rituximab and oral melphalan and prednisone in newly diagnosed multiple myeloma.

Clonotypic B lymphocytes may underlie relapse of patients with multiple myeloma. Rituximab, a CD20 monoclonal antibody, may result in eradication of the monoclonal B cells. We conducted a phase II study of rituximab in combination with melphalan and prednisone therapy (MP) followed by rituximab maintenance in newly diagnosed multiple myeloma patients.