Juno Therapeutics (JUNO) halted a clinical trial involving its most advanced CAR-T therapy for the second time in five months after two cancer patients developed brain swelling and died, the company said Wednesday.

Juno shares plunged 44% to $16.65 in Wednesday premarket trading.

The two patients, both diagnosed with acute lymphoblastic leukemia, were treated with Juno's JCAR015, a new form of cancer immunotherapy in which a patient's own T cells are removed and then engineered to identify and kill malignant blood cancer cells.

Juno did not say what caused the brain swelling in the patients, but the clinical trial in which they were enrolled, dubbed Rocket, has been stopped and the U.S. Food and Drug Administration was notified.

Last July, two other patients enrolled in the same clinical trial died from brain swelling following treatment with JCAR015.

The trial was halted for a short time but was allowed to resume relatively quickly after Juno blamed the deaths on the chemotherapy agent fludarabine interacting with JCAR015. Fludarabine was used to clear out a patient's old T cells in order for the re-engineered T cells in the CAR-T to grow and take hold.

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