One year follow-up results of phase I/II clinical trial for combined treatment of chronic wounds with dermal equivalent-assisted skin autograft

A randomized controlled phase I/II clinical trial was designed to evaluate the safety and efficacy of encapsulated human umbilical cord mesenchymal stem cells in a plasma-derived biomaterial for regenerative endodontic procedures (REPs) in mature permanent teeth with apical lesions. The trial included 36 patients with mature incisors, canines, or mandibular premolars showing pulp necrosis and apical periodontitis. Patients were randomly and equally allocated between experimental (REP) or conventional root canal treatment (ENDO) groups. On the first visit, cavity access and mechanical preparation of the root canal were performed. Calcium hydroxide medication was used, and the cavity was sealed. Three weeks later, patients were treated following their assigned protocol of ENDO or REP. Clinical follow-up examinations were performed at 6 and 12 mo. Categorical variables were evaluated by Fisher’s exact test. Quantitative variables were compared using the Mann-Whitney test. The evolution over time of the percentage of perfusion units and the dimensions of lesion and cortical compromise were explored. After the 12-mo follow-up, no adverse events were reported, and the patients showed 100% clinical efficacy in both groups. Interestingly, in the REP group, the perfusion unit percentage measured by laser Doppler flowmetry revealed an increase from 60.6% to 78.1% between baseline and 12-mo follow-up. Sensitivity tests revealed an increase of the positive pulp response in the REP group at 12-mo follow-up (from 6% to 56% on the cold test, from 0% to 28% on the hot test, and from 17% to 50% on the electrical test). We present the first clinical safety and efficacy evidence of the endodontic use of allogenic umbilical cord mesenchymal stem cells encapsulated in a plasma-derived biomaterial. The innovative approach, based on biological principles that promote dentin-pulp regeneration, presents a promising alternative for the treatment of periapical pathology (ClinicalTrials.gov NCT03102879).

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Total Lymphoid Irradiation and High-Dose Chemotherapy with Autologous Blood Stem-Cell Transplantation for Relapsed and Refractory Hodgkin Lymphoma: Excellent Disease Control and Long-Term Survival Rates

Blood ◽

10.1182/blood.v120.21.2024.2024 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2024-2024

Author(s):

Ryan D. Gentzler ◽

Andrew M. Evens ◽

Alfred W. Rademaker ◽

Bharat B Mittal ◽

Adam M. Petrich ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Survival Rates ◽

Standard Of Care ◽

High Dose Chemotherapy ◽

Salvage Chemotherapy ◽

High Dose ◽

Term Survival

Abstract Abstract 2024 Background: For patients with relapsed or refractory HL, salvage chemotherapy followed by aHSCT is the standard of care. Our group previously reported excellent clinical outcomes with accelerated hyperfractionated TLI followed by high-dose chemotherapy and aHSCT (Ann of Oncol. 16:679, 2007). This strategy has been adopted as the standard at our institution for eligible individuals and we now report long-term outcomes of patients previously reported on the phase I/II clinical trial in addition to those who were subsequently treated as standard of care. Patients and methods: Patients with biopsy confirmed relapsed/refractory classical HL who previously received no more than 20 Gy were eligible. Salvage chemotherapy was chosen by the patient's treating physician. All patients received accelerated hyperfractionated TLI prior to transplantation administered twice daily at 150 cGy, five days/week for 10 days. The morning dose was delivered to all nodal sites including the spleen, and the afternoon dose was delivered to all sites of previous and current disease. The goal was to treat uninvolved nodal sites and spleen to 1500 cGy and sites of current and previous disease to 3000 cGy. Conditioning chemotherapy consisted of high-dose carboplatin, cyclophosphamide, and etoposide. All patients received carboplatin 450 mg/m2 by continuous intravenous infusion (CIV) on days –6 to –4 (total dose = 1350 mg/m2) and cyclophosphamide 60 mg/kg/day over 1 h on days –3 and –2 (total dose = 120 mg/kg). Patients on the phase I portion of the trial received escalating doses of etoposide by CIV from days –6 to –4. Initial dosing levels were 400 mg/m2/day, 450 mg/m2/day, 500 mg/m2/day, 600 mg/m2/day and 700 mg/m2/day. Those treated on the phase II portion of the clinical trial or subsequent to the closing of the trial were treated with etoposide 700 mg/m2/day for a total of 2100 mg/m2. Results: 52 patients with relapsed/refractory HL at Northwestern University were treated with TLI and aHSCT from 1993 to January 2011. One patient was lost to follow-up immediately post-transplant. 51 patients were included in this analysis and had a median follow-up of 47 months (range: 0.07–204 months). Thirty patients were treated on a previously reported prospective phase I/II clinical trial. Most patients had nodular sclerosis histology (n=39, 76%) and more than half had primary induction failure (PIF; n=29). Among patients who achieved a CR with induction, 62% relapsed within one year. The most common salvage regimens were ESHAP and ICE chemotherapy and most had received two lines of chemotherapy prior to aHSCT. Only 21 patients (41%) achieved a complete response (CR) with salvage therapy and in most cases (n=31, 61%), response was determined by functional imaging prior to aHSCT. The 10-year PFS and OS for all patients were 56% and 54%, respectively. Ten-year PFS and OS for patients with PIF was 53%, compared with 63% and 59%, respectively, for those with relapsed disease (p=0.13 and p=0.20, respectively). Patients who had incomplete responses to salvage therapy had a 10-year PFS and OS of 41% and 39%, respectively, compared to 76% and 81%, respectively, for those who achieved a CR (p=0.1 and p=0.056, respectively). Treatment-related mortality within the first 100 days was observed in one patient. Five patients (10%) developed secondary malignancies; three developed MDS (one who had received MOPP induction died with MDS; one had relapsed HL post-aHSCT and died of AML and one is alive with MDS 3+ yrs post-diagnosis). There was one case each of T-cell lymphoma (7 months post-aHSCT) and melanoma. Conclusions: Sequential TLI/chemotherapy conditioning for relapsed/refractory HL for patients with limited or no prior radiotherapy continues to be associated with excellent disease control and long-term survival rates including high-risk populations such as PIF and chemotherapy-resistant disease. Disclosures: No relevant conflicts of interest to declare.

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The effectiveness of an individually tailored oral health educational programme on oral hygiene behaviour in patients with periodontal disease: a blinded randomized-controlled clinical trial (one-year follow-up)

Journal Of Clinical Periodontology ◽

10.1111/j.1600-051x.2009.01453.x ◽

2009 ◽

Vol 36 (12) ◽

pp. 1025-1034 ◽

Cited By ~ 76

Author(s):

B. Jönsson ◽

K. Öhrn ◽

N. Oscarson ◽

P. Lindberg

Keyword(s):

Clinical Trial ◽

Oral Health ◽

Oral Hygiene ◽

Educational Programme ◽

Controlled Clinical Trial ◽

Randomized Controlled Clinical Trial ◽

Randomized Controlled ◽

Hygiene Behaviour ◽

One Year

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One-Year Follow-Up of a Randomized Clinical Trial Comparing Flexion Distraction with an Exercise Program for Chronic Low-Back Pain

The Journal of Alternative and Complementary Medicine ◽

10.1089/acm.2006.12.659 ◽

2006 ◽

Vol 12 (7) ◽

pp. 659-668 ◽

Cited By ~ 43

Author(s):

Jerrilyn A. Cambron ◽

M. Ram Gudavalli ◽

Donald Hedeker ◽

Marion McGregor ◽

James Jedlicka ◽

...

Keyword(s):

Clinical Trial ◽

Low Back Pain ◽

Back Pain ◽

Randomized Clinical Trial ◽

Chronic Low Back Pain ◽

Exercise Program ◽

Low Back ◽

One Year

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A randomized trial of telemedicine for migraine management

Cephalalgia ◽

10.1177/0333102419868250 ◽

2019 ◽

Vol 39 (12) ◽

pp. 1577-1585 ◽

Cited By ~ 16

Author(s):

Deborah I Friedman ◽

Balaraman Rajan ◽

Abraham Seidmann

Keyword(s):

Clinical Trial ◽

Clinical Effectiveness ◽

Care Physician ◽

Patient Perceptions ◽

Office Visits ◽

Physician Productivity ◽

One Year ◽

Headache Center ◽

Severe Migraine

Objective To determine whether synchronous video-based telemedicine visits with specialists are feasible and to evaluate clinical effectiveness, patient perceptions, and other benefits of telemedicine visits for follow-up migraine care in a tertiary headache center. Design A one-year, randomized clinical trial. Results Fifty patients were screened and 45 entered the study (43 women, two men). Out of 96 scheduled visits, 89 were successfully conducted using telemedicine. Eighteen patients (out of 22) in the telemedicine cohort and 12 patients (out of 23) in the in-office cohort completed the study. In this small study, clinical outcomes, namely improvement in MIDAS, number of headache days, and average severity at 12 months for participants in the telemedicine group, were not different from those in the in-office group. Convenience was rated higher and visit times were shorter in the telemedicine group. Conclusions In this cohort of patients with severe migraine-related disability, telemedicine was a feasible mode of treatment and an effective alternative to in-office visits for follow-up migraine care. Physician productivity could be higher with telemedicine, and patients may get better access because of its convenience. Trial Registration This study is listed on ClinicalTrials.gov (NCT01706003).

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Phase I study of lurbinectedin (PM11083) in patients with advanced AML and MDS.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18521 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18521-e18521 ◽

Cited By ~ 1

Author(s):

Christopher Brent Benton ◽

Jose Rodriguez Diaz -Pavon ◽

Abhishek Maiti ◽

Naval Guastad Daver ◽

Farhad Ravandi ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Phase I ◽

Single Agent ◽

Dna Minor Groove ◽

Oral Herpes ◽

Risk Patients ◽

Md Anderson ◽

Dose Levels

e18521 Background: The FDA-approved drug trabectedin is a DNA minor groove binder (MGB) with activity against translocation-associated sarcomas. Lurbinectedin is a next-generation MGB, with activity against myeloid leukemia cells. A phase I clinical trial was initiated to determine recommended doses in MDS/AML. Further assessment of its safety, tolerability, and pharmacogenetics were studied. Methods: In total, 42 patients with relapsed/refractory MDS/AML received lurbinectedin, using a 3+3 study design. It was administered as a 1-hour IV infusion first at 3.5, 5, 6, and 7mg per dose on days 1 and 8. Subsequently, it was administered on days 1, 2, and 3, using 1, 1.5, 2, or 3mg per dose per patient. Results: Three patients had dose-limiting toxicities (DLTs), which were rhabdomyolysis (up to gr 4), hyperbilirubinemia (gr 3), and oral herpes (gr 3). All DLTs occurred in the 6 and 7mg cohorts. Adverse events included febrile neutropenia/infections (n = 3), GI (n = 6) and pulmonary (n = 2) toxicity, hyperhidrosis (n = 1), and QT prolongation (n = 1). Overall, 33 of 42 patients (79%) had reduction of blasts in peripheral blood (PB) or bone marrow (BM) at nadir, including 23 (55%) with > 50% reduction in PB blasts alone (n = 18) or both BM and PB blasts (n = 5). One patient had PR, 2 patients had morphologic leukemia-free survival, and most (n = 30) were discontinued for progressive disease. Early deaths occurred from disease-related causes, not attributable to lurbinectedin. Thirty-two patients treated at MD Anderson were analyzed for clinical characteristics and responses. Notably, among patients with follow-up bone marrow biopsy, those with a cytogenetic abnormality at chromosome 11q21-23 had significantly greater bone marrow blast reduction than those without such abnormality (change in percentage blasts: -31±14% [n = 4] vs. 8±8% [n = 16], respectively; P= 0.04). Conclusions: Lurbinectedin is generally safe and tolerated at dose levels tested. While no sustained remissions > 3 cycles were observed in these highest-risk patients, single-agent lurbinectedin was transiently leukemia suppressive for some patients, including some with abnormal chr11q or TP53 mutation. Rational combinations and situational uses of lurbinectedin are under consideration. Clinical trial information: NCT01314599.

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Survivin-responsive conditionally replicating adenovirus for patients with advanced sarcoma demonstrated potent and long-term efficacy and high safety in a phase I clinical trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.11512 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 11512-11512

Author(s):

Satoshi Nagano ◽

Toshitaka Futagawa ◽

Eriko Sumi ◽

Nobuhiro Ijichi ◽

Munekazu Yamaguchi ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Phase I Clinical Trial ◽

Oncolytic Viruses ◽

High Dose ◽

Liver Transaminase ◽

Musculoskeletal Tumors ◽

Choi Criteria

11512 Background: Whereas one of oncolytic viruses (OVs), inducing selective tumor killing and systemic anti-tumor immunity, was approved by FDA in 2015, the best OV that more safely and efficiently treats intractable cancers has not been successfully developed. By our platform technology to efficiently construct next-generation OVs, i.e., “conditionally replicating adenoviruses (CRAs) that target and/or treat tumor cells with multiple factors” (m-CRAs), we identified that among candidates, survivin-responsive m-CRAs (Surv.m-CRAs) exhibited the most potent antitumor efficacy and cancer selectivity ( i.e., safety) in preclinical studies ( Cancer Res, 2005 et al.). Here we present the data of First-In-Human phase I clinical trial of Surv.m-CRA-1 for musculoskeletal tumors (MST). Methods: This single-arm, open label study included 9 patients with unresectable and advanced MST. Patients underwent a single intratumoral injection of either 1×10^10 viral particle (vp) (low), 1×10^11 vp (mid) or 1×10^12 vp (high). The primary endpoints were safety and tolerability. The secondary endpoints included the local control of treated tumor at one month, defined by RECIST and Choi criteria, analysis of dissemination of Surv.m-CRA-1, serum cytokine and adenoviral antibody. Long-term follow-up was done in some patients. Results: Four patients (44.4%) had grade 3 or higher adverse events, including lymphopenia, leukocytopenia and mildly elevated liver transaminase in 2, 1 and 1 patient, respectively. Virus excretions, including second peak of viremia from viral replication in tumor, were observed in 1, 2 and 3 patients of low, mid and high dose, respectively. Out of 9 patients, 5 PR, 3 SD and 1 PD by Choi, and 8 SD and 1 PD by RECIST were observed. During follow-up, another 1 and 2 patients became PR by Choi and RECIST, respectively. Of note, long-term PR (over 2 years) after a single injection of Surv.m-CRA-1 was achieved in two chordoma cases in low dose. Conclusions: Surv.m-CRA-1 was well tolerated and showed antitumor activity for prolonged periods against advanced MST. We about to start Phase I/II study of multiple injections of Surv.m-CRA-1 for advanced solid tumors in two-arms for musculoskeletal tumors and pancreatic cancer. Clinical trial information: R000026464 .

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