Cell therapy receives RMAT designation

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.  

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.  

Photo by Rhoda Baer

The US Food and Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation for romyelocel-L, a myeloid progenitor cell therapy that doesn’t require HLA matching.

Romyelocel-L (CLT-008) is being developed as prophylaxis for serious bacterial and fungal infections in patients with de novo acute myeloid leukemia (AML) who develop neutropenia while receiving induction chemotherapy.

The FDA grants RMAT designation to therapies intended to treat serious or life-threatening conditions if there is preliminary clinical evidence that the therapies could address unmet medical needs.

RMAT designation provides similar advantages as breakthrough therapy designation, including early interactions with the FDA to discuss potential ways to accelerate the development of a therapy toward regulatory approval.

The FDA granted romyelocel-L RMAT designation based on a randomized, phase 2 trial of newly diagnosed AML patients who received induction consisting of cytarabine and an anthracycline.

Results from this trial were presented at the 2018 ASCO Annual Meeting (abstract 7043).

The trial enrolled 163 AML patients and randomized them, on the first day of induction, to receive:

• Daily granulocyte colony-stimulating factor (G-CSF) starting on day 14 (n=84)
• Romyelocel-L (7.5 x 10⁶cells/kg) on day 9 plus daily G-CSF starting on day 14 (n=79).

Patients received G-CSF until neutrophil recovery to at least 500/µL.

Baseline characteristics were well balanced between the treatment arms.

There were 120 evaluable patients—59 in the romyelocel-L arm and 61 in the control arm.

The study’s primary endpoint was days in a febrile episode (DFE). The mean DFE from day 9 to 28 was 6.46 days in the romyelocel-L arm and 6.86 days in the control arm (P=0.350). The mean DFE for days 15 to 28 was 2.36 and 3.90, respectively (P=0.020).

The incidence of microbiologically or clinically diagnosed infection from day 9 to 28 was 35.6% in the romyelocel-L arm and 47.5% in the control arm, a decrease of 25% (P=0.089).

From day 15 to 28 the incidence of infection was 6.8% in the romyelocel-L arm and 27.9% in the control arm, a decrease of 76% (P=0.002).

There were no infectious deaths in the romyelocel-L arm but 2 deaths attributed to pneumonia in the control arm.

The mean hospital stay was 25.5 days in the romyelocel-L arm and 28.7 days in the control arm (P=0.002).

The proportion of patients with serious adverse events (AEs) was 14% in the romyelocel-L arm and 18% in the control arm. The proportion of patients with infectious serious AEs was 50% and 77%, respectively.

The most frequent treatment-emergent AEs (in the romyelocel-L and control arms, respectively) were febrile neutropenia (31.4% and 31%), diarrhea (25.7% and 32.4%), hypokalemia (31.4% and 25.4%), hypophosphatemia (21.4% and 23.9%), and pyrexia (22.9% and 22.5%).

There were no cases of graft-versus-host disease.