Product ‘solves engraftment problem’ with UCBT

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.

Umbilical cord blood donation

Photo courtesy of NHS

SAN DIEGO—A product that promotes CD34 expansion has solved the problem of poor engraftment associated with umbilical cord blood transplant (UCBT), according to a speaker at the 2015 BMT Tandem Meetings.

John Wagner, MD, of the University of Minnesota in Minneapolis, supported this statement with early results from trials of HSC835, cord

blood units in which CD34 cells were expanded using the aryl hydrocarbon

receptor antagonist StemRegenin 1.

Dr Wagner and his colleagues conducted phase 1 and 2 trials of HSC835, which were supported by Novartis, the company developing the product.

Dr Wagner presented results of these trials at the BMT Tandem Meetings as abstract 29.*

The phase 1 trial included 18 patients who received double UCBT after myeloablative conditioning. They received an unmanipulated cord blood unit and an HSC835 unit.

In the phase 2 trial, 3 patients received a single HSC835 unit after myeloablative conditioning, and 3 received an HSC835 unit after non-myeloablative conditioning.

Manufacturing HSC835 took 15 days. Following expansion, the median CD34 cell dose increased 346-fold, and the median total nucleated cell (TNC) dose increased 848-fold.

Twenty-eight HSC835 products were produced, but 4 of them were not infused. Two products were contaminated, 1 was not infused due to patient relapse, and 1 product failed to expand. Dr Wagner noted that the failed unit started out at 50% viability, whereas the other units started at about 90% viability.

Phase 1

Eighteen patients were treated in the phase 1 trial. Eleven had acute lymphoblastic leukemia, 5 had acute myeloid leukemia, and 2 had myelodysplastic syndromes. The median age was 28 (range, 12 to 53).

The median TNC dose was 2.5 x 10⁷/kg for the unmanipulated cord blood unit and 5.1 x 10⁷/kg for the HSC835 unit. The median CD34 count was 0.4 x 10⁶/kg and 17.4 x 10⁶/kg, respectively. And the median CD3 count was 8.5 x 10⁶/kg and 2.5 x 10⁶/kg, respectively.

Most units were a 5/6 HLA match—50% for the unmanipulated unit and 67% for the HSC835 unit. Forty-four percent and 22% of the units, respectively, were 4/6 matches. And 6% and 11%, respectively, were 6/6 matches.

Neutrophil recovery was 100%, and the median time to recovery was 14.5 days.

Dr Wagner compared this to results in 121 matched historical controls who received UCBT with 2 unmanipulated units. Of those patients, 86% achieved neutrophil engraftment, and the median time to engraftment was 25 days (P<0.001).

In the current study, 6 patients had complete chimerism with HSC835, 6 had complete chimerism with the unmanipulated unit, and 6 had dual chimerism. In the dual-chimerism patients, both units were present, but all the T cells were derived from the unmanipulated unit.

“When we look at those patients who had engraftment of HSC835, whether it be this dual chimerism or complete chimerism, you see there is a very rapid recovery of 10.5 days, as compared to the historical control [recovery time] of 25 days,” Dr Wagner said. “And those that engrafted with the unmanipulated unit fall right where you’d expect them; that is, with the historical controls [23 days].”

Dr Wagner noted that the CD34 dose correlated with the pace of neutrophil recovery in patients who engrafted with the HSC835 unit, and patients with dual chimerism had the fastest neutrophil recovery.

Furthermore, the HSC835 unit predominated more than expected (P=0.05), winning out over the cord blood unit with a higher CD3 dose a disproportionate amount of time. The unit with a higher CD3 dose typically predominates two-thirds of the time in double UCBT.

“[These results] gave us enough information to say that [HSC835] could be a stand-alone product,” Dr Wagner said.

Phase 2

For phase 2, the researchers used a single HSC835 unit. They chose the lesser of 2 cord blood units (keeping the better unit as a backup), expanded it, and infused the resulting HSC835 unit into 3 patients who received myeloablative conditioning and 3 patients who did not.

In patients who received myeloablative conditioning, chimerism was complete at days 8, 12, and 14. Among the patients who received non-myeloablative conditioning, 1 had mixed chimerism at day 6. The other 2 had complete chimerism at days 5 and 7.

“So in conclusion, we believe that HSC835 is safe and effective in speeding neutrophil recovery after cord blood transplant,” Dr Wagner said. “These are very promising early results that compel us now to explore the single expanded product.”

Dr Wagner added that other considerations for HSC835 are that it may reduce the unit selection threshold, improve HLA match, enable re-cryopreservation (for transplant delays, backup, or multiple dosing), and perhaps allow for reduced-intensity conditioning with “mega-dose” grafts.

*Information in the abstract differs from that presented at the meeting.