One-month follow up of a randomized clinical trial-phase II study in 6 to <24 months old Indonesian subjects: Safety and immunogenicity of Vi-DT Typhoid Conjugate Vaccine

Abstract Background Premature ovarian failure (POF) is characterized by the loss of ovarian activity before the age of 40 years. Stem cell therapy has the capability to create a regenerative microenvironment and is a proposed treatment for POF-related infertility due to the presence of renewal folliculogenesis and germ cells in the adult ovaries. In this study, we assessed the safety, feasibility, efficacy and dose adjustment of autologous adipose-derived stromal cells (ADSCs) and their ability to improve ovarian function in POF patients. Methods This study was a non-randomized clinical trial, phase I. Nine women with a definitive diagnosis of POF were divided into three groups (n = 3 per group) that received either 5 × 106, 10 × 106, or 15 × 106 autologous ADSCs suspension transplanted in the one ovary. Participants were followed-up at 24 h after the transplantation, and at 1 and 2 weeks, and 1, 2, 3, 6, and 12 months after the transplantation. The primary objective was to evaluate the safety of ADSCs transplantation. Secondary objectives included the effects of ADSCs transplantation on the resumption of menstruation, hormones level (Follicle-stimulating hormone (FSH) and anti-Müllerian hormone), ovarian function (Antral follicle count and ovary volume by ultrasonography evaluation) as well as dose escalation. Results Participants had not shown any early-onset possible side effects and secondary complications during follow-up. The menstruation resumption was observed in four patients which established for several months. In the 15 × 106 group, two POF patients had a return of menstruation second months after the intervention. Two other POF patients in 5 × 106 and 10 × 106 cell groups reported menstruation resumption at 1 month after the intervention. We observed decreased serum FSH levels of less than 25 IU/l in four patients. In two patients in 5 × 106 and 10 × 106 cell groups, serum FSH showed an inconsistent decline during a 1 year follow up after ADSCs transplantation. The ovarian volume, AMH, and AFC were variable during the follow-up and no significant differences between cell groups (p > 0.05). Conclusions We showed the intra-ovarian embedding of ADSCs is safe and feasible and is associated with an inconsistent decline in serum FSH. This should be further investigated with a large RCT. Trial registration NCT02603744, Registered 13 November 2015 - Retrospectively registered, http://www.Clinicaltrials.gov

Download Full-text

A phase II study investigating biological effects of maintenance usage of hydroxychloroquine on Par-4 levels in patients with resected tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3085 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3085-3085

Author(s):

Peng Wang ◽

Ravshan Burikhanov ◽

Heidi Weiss ◽

Rani Jayswal ◽

Susanne M. Arnold ◽

...

Keyword(s):

Clinical Trial ◽

Disease Progression ◽

Phase Ii ◽

Interim Analysis ◽

Phase Ii Study ◽

Biological Effects ◽

Fold Increase ◽

Two Stage ◽

Stage Design

3085 Background: Hydroxychloroquine (HCQ) is an inducer of the tumor suppressor Par-4 (prostate apoptosis response-4) secretion from normal cells. Secreted Par-4 causes paracrine apoptosis of tumor cells in mice. Established dosing of HCQ 200 mg bid induces Par-4 secretion but not the autophagy-inhibition marker p62 and correlates with apoptosis induction in patients' tumors. Methods: This is a single-arm, single institute phase II study to characterize the biological effects of 3-months of HCQ at fixed-dose (200 mg p.o. twice a day) on plasma Par-4 levels in adults with resected solid tumors. The primary endpoint is proportion of patients who will exhibit a two-fold increase in Par-4 levels from baseline compared to 3 months of follow-up. 12-month progression free survival (PFS) is one of the secondary endpoints. A Simon's two-stage design was used to test the null hypothesis that the proportion of patients exhibiting a two-fold increase in Par-4 is equal to 50% compared to 70% using a one-sided alternative. These hypothesized assumptions are based on a small pilot human data and from a phase I clinical trial on a small number of patients (n = 9). The first stage of interim analysis will be performed after a total of 15 patients have been accrued. If there are eight or fewer responses occurred, the study will be stopped. Otherwise, 28 additional patients will be accrued for a total of 43 subjects. Results: A total of 19 patients were enrolled in the trial. Per protocol, the interim analysis and stopping boundary is based on the first 15 patients. A total of 4 out of 15 patients (26.7%) 95% CI: 8% - 55% exhibited a >2-fold increase in Par-4 levels at 3 months. This did not surpass the stopping bound for futility and thus indicates stopping of patient accrual based on the assumptions used for the Simon's two-stage design. 7 out of 19 patients (36.8%) 95% CI: 16% - 62% who exhibited at least a 2-fold increase at either 2 or 3 months of follow-up, 50% (95% CI: 26% - 74%) and 56% (95% CI: 31% -79%) exhibited a 1.5-fold and 1.25-fold increase respectively. To date, 10/19 patients finished 12-month follow-up, 4/19 and 5/19 finished 6-month and 3-month follow up respectively. 2 of 12 patients with less than 2-fold increase of Par-4 developed disease progression. None of 7 patients with 2-fold increase of Par-4 showed disease progression. Conclusions: Despite that the study was terminated prematurely, to our knowledge this is the first study in human to identify dynamic changes of serum Par-4 while on long-term of usage of HCQ. We also demonstrate trend of PFS benefit especially for subjects having 2-fold increase of Par-4 induction. Identification of tumors more Par-4 sensitive and predictive biomarkers of Par-4 induction are necessary to continue our investigation. Clinical trial information: NCT02232243.

Download Full-text