Cell Therapy Clinical Trials in 2008 – part II

by Alexey Bersenev on December 10, 2008 · 4 comments

in clinical trials and cases

I continue to overview results of the most important clinical trials published in 2008 based on my opinion. Part I you can read here.

diabetes:

Autologous umbilical cord blood infusion for type 1 diabetes

We recently embarked on a pilot study to document the safety and potential efficacy of autologous UCB infusion in subjects with T1D. Under this protocol, patients recently diagnosed with the disease and for whom autologous cord blood is stored, undergo infusion. Studies are performed before infusion and every 3–6 months post-infusion for immunologic and metabolic assessment. To date 15 autologous infusions have been performed.
Preliminary observations suggest that autologous cord blood transfusion is safe and provides some slowing of the loss of endogenous insulin production in children with T1D.
Prolonged follow up and additional mechanistic efforts are urgently needed to determine if umbilical cord blood derived stem cells can be used as part of safe and effective therapies for T1D.

read about one more

MSC expansion for HSC engraftment:

Transplantation of ex-vivo culture-expanded parental haploidentical mesenchymal stem cells to promote engraftment in pediatric recipients of unrelated donor umbilical cord blood: results of a phase I–II clinical trial

In an attempt to speed hematopoietic recovery, 15 pediatric patients with high-risk acute leukemia were enrolled on a single-institution phase I–II clinical trial in which ex-vivo culture-expanded MSCs from haploidentical parental donors were infused at the time of UCBT. Eight patients received MSCs on day 0, with three patients having a second dose infused on day 21. No serious adverse events were observed with any MSC infusion. All eight evaluable patients achieved neutrophil engraftment at a median of 19 days. Probability of platelet engraftment was 75%, at a median of 53 days. With a median follow-up of 6.8 years, five patients remain alive and disease free. The results of this pilot study show that infusion of ex-vivo culture-expanded haploidentical MSCs into unrelated pediatric UCBT recipients can be performed safely. This encouraging safety profile with haploidentical MSCs supports the investigation of unrelated ‘off the shelf’ allogeneic HLA-mismatched MSC products.


liver failure:

Controlled trials in hepatitis B virus-related decompensate liver cirrhosis: peripheral blood monocyte transplant versus granulocyte-colony-stimulating factor mobilization therapy

A total of 40 subjects (31 men and nine females, age range 21-71 years) was recruited to two groups. Group 1 received granulocyte-colony-stimulating factor (G-CSF) mobilization, PBMC collection by leukapheresis and PBMC transplant therapy. Group 2 received G-CSF mobilization for 4 days. At baseline and 6 months after treatment, liver function of the two groups was monitored by blood examination and ultrasonagraphy.
Both groups gained significant improvement in liver synthetic function, such as serum albumin and prothrombin time, from baseline to 6 months after treatment (P<0.01). However, there was no significant difference in alanine aminotransferase, aspartate aminotransferase and total bilirubin in both groups (P>0.05). Compared with group 2, a significantly improved liver function was observed in group 1, including elevated serum albumin level and a decreased CTP score (P<0.05). No major adverse effects were noted.
Autologous PBMC transplantation could be considered as a novel and alternative treatment for patients with decompensated liver cirrhosis.

read about one more

cancer:

Allogeneic hematopoietic cell transplantation for metastatic breast cancer

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3–64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens.
A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09).
These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.

A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma

This is a phase II clinical trial investigating the safety and efficacy of intravenous vaccination with mature autologous dendritic cells (DCs) pulsed ex vivo with a liver tumor cell line lysate (HepG2) in patients with advanced hepatocellular carcinoma (HCC).
Thirty-five patients with advanced HCC and not suitable for radical or loco-regional therapies received a maximum of six DC vaccinations each at 3-week intervals. In total, 134 DC infusions were administered with no significant toxicity and no evidence of autoimmunity. Twenty-five patients who received at least three vaccine infusions were assessed clinically for response.
In several cases there was induction of T cell responses to the vaccine and/or AFP following vaccination. Conclusion: Autologous DC vaccination in patients with HCC is safe and well tolerated with evidence of antitumor efficacy assessed radiologically and serologically, with generation of antigen-specific immune responses in some cases.

Infusion of the allogeneic cell line NK-92 in patients with advanced renal cell cancer or melanoma: a phase I trial

In this phase I dose-escalation study, the feasibility of large-scale expansion and safety of administering ex vivo-expanded NK-92 cells as allogeneic cellular immunotherapy in patients with refractory renal cell cancer and melanoma were determined.
Twelve patients (aged 31-74 years) were enrolled… Eleven patients had refractory metastatic renal cell cancer; one patient had refractory metastatic melanoma.
One patient was alive with disease at 4 years post-NK-92 infusion. The one metastatic melanoma patient had a minor response during the study period. One other patient exhibited a mixed response.
This study establishes the feasibility of large-scale expansion and safety of administering NK-92 cells as allogeneic cellular immunotherapy in advanced cancer patients and serves as a platform for future study of this novel natural killer (NK)-cell based therapy.

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more clinical trials

picture credit: American Association for Laboratory Animal Science

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{ 4 comments… read them below or add one }

Jim H December 10, 2008 at 12:45 pm

Alex,

Great stuff. I have all sorts of searches set up for this kind of thing and there are definitely new trials I’d never heard of in here.

Reply

Alex December 10, 2008 at 3:50 pm

Thanks Jim,
it’s was not so easy for me to pick most interesting trials from everything that i dugg in PubMed

Reply

Mitch K September 2, 2009 at 1:32 pm

Alex,

Thank you compiling this information. I am wondering about one thing: do you have any sort of graph that shows # cell therapy trials (ideally broken down by disease (cancer, HIV, hereditary deficiancies) andmethodology-HCT, gene modified cells, etc. etc) vs. year? I think it would be very useful to see how and in what way the field is expanding

Reply

Alex September 3, 2009 at 5:14 pm

Mitch,
Yes i think it will be great if somebody will do this work. But it’s very hard, because the failure of online databases and registries. Information on http://www.clinicaltrials.gov definitely not enough to complete the real picture.
Christopher Scott did some of this work and summarized it here
http://shirleyahn.wordpress.com/2009/03/21/the-stem-cell-clinical-trials-index-2/
This is total, not in details, but one of the first attempts to track cell therapy trials and visualize in graphs.

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