NEWS
Crizotinib Approved for Relapsed / Refractory Systemic ALCL
Crizotinib has been approved by the U . S . Food and Drug Administration ( FDA ) for the treatment of children older than one year and young adults with relapsed or refractory systemic anaplastic large cell lymphoma ( ALCL ) that is ALK-positive .
This decision was based on results from Study ADVL0912 , in which 26 patients between the ages of one and 21 received crizotinib 280 mg / m 2 or 165 mg / m 2 orally twice daily until disease progression or unacceptable toxicity . Patients were permitted to discontinue crizotinib to undergo hematopoietic cell transplantation .
The complete remission rate was 81 %, with an objective response rate of 88 %. Of the 23 patients who responded to therapy , 39 % maintained response for at least six months , and 22 % for at least one year .
Gastrointestinal toxicity occurred in 92 % of patients , and ocular toxicity occurred in 65 %. The most common adverse events ( AEs ), occurring in ≥35 % of patients , included diarrhea , vomiting , nausea , vision disorder , headache , musculoskeletal pain , stomatitis , fatigue , decreased appetite , pyrexia , abdominal pain , cough , and pruritus . Grade 3-4 laboratory abnormalities that occurred in ≥15 % of patients were neutropenia , lymphopenia , and thrombocytopenia . Source : FDA . gov , January 14 , 2021 .
FDA Issues Guidance for Measuring Viscoelasticity Amid COVID-19 Pandemic
The FDA has issued immediate guidance for expanding the availability and capability of coagulation systems for measuring whole blood viscoelastic properties to assess hemostasis . This guidance is intended to remain in effect for the duration of the COVID-19 public health emergency .
The recommendations apply to legally marketed , multipurpose systems for in vitro coagulation studies and coagulation systems for the measurement of whole blood viscoelastic properties .
Currently , no coagulation system is cleared or approved by the FDA for measuring whole blood viscoelastic properties in a hospital setting to help clinicians identify changes in coagulation status , including after surgical procedures or traumatic injuries . In addition , patients who are hospitalized with COVID-19 – associated coagulopathy commonly display laboratory abnormalities such as mild thrombocytopenia , increased D-dimer levels , increased fibrin degradation products , and prolonged prothrombin time .
“[ The ] FDA believes the policy set forth in this guidance will help address these urgent public health concerns by helping to expand the availability and capability of coagulation systems for measurement of whole blood viscoelastic properties ,” the authors of the guidance document stated . Source : FDA . gov , January 28 , 2021 .
VLX-1005 Receives Orphan Drug Designation
The FDA granted orphan drug designation to VLX-1005 as thrombosis prophylaxis in patients with heparin-induced thrombocytopenia ( HIT ).
According to its manufacturer , Veralox Therapeutics , preclinical data have shown that VLX-1005 has the potential to halt immune-driven platelet activation and thrombosis . VLX-1005 is a first-in-class , selective small molecule inhibitor of 12-lipoxygenase , a key target within the arachidonic acid pathway .
“ We believe VLX-1005 has great potential to be the first disease modifying therapy for HIT in over 20 years ,” said Matthew B . Boxer , PhD , chief operating officer of Veralox Therapeutics . Source : Veralox Therapeutics press release , January 26 , 2021 .
FDA Accepts IND Application for PBCAR19B
The FDA cleared Precision BioSciences ’ Investigational New Drug ( IND ) application for its chimeric antigen receptor ( CAR ) T-cell therapy PBCAR19B . The company will initiate a phase I trial evaluating the safety and clinical activity of PBCAR19B at increasing flat dose levels ( 2.7-8.1 × 10 8 CAR T cells ) in patients with relapsed or refractory non-Hodgkin lymphoma .
Manufactured from healthy donor cells using the company ’ s proprietary ARCUS genome editing platform , PBCAR19B is designed to improve the persistence of allogeneic CAR T cells after infusion by preventing rejection by a patient ’ s T cells and natural killer cells .
“ We are pleased to receive IND clearance for PBCAR- 19B , which has shown in preclinical studies to delay both T cell and natural killer cell-mediated allogeneic rejection ,” said Matt Kane , CEO of Precision BioSciences . “ We believe that the ability to reduce rejection by both cell types holds potential for improved persistence of allogeneic CAR T cells .” Source : Precision BioSciences press release , January 19 , 2021 .
IND Application Cleared for VOR33 in CD33 + Acute Myeloid Leukemia
The FDA cleared Vor Biopharma ’ s IND application for its hematopoietic cell therapy VOR33 . This decision allows the company to initiate a phase I / IIa clinical trial evaluating tolerability and feasibility of VOR33 in patients with CD33-positive acute myeloid leukemia ( AML ) who are at high risk of relapse .
VOR33 consists of hematopoietic cells engineered to lack the CD33 protein . Following treatment with VOR33 , patients will be eligible to receive the FDA-approved CD33-directed antibody drug conjugate gemtuzumab ozogamicin to prolong leukemia-free survival and determine if VOR33 protects against the myelosuppression that typically accompanies treatment with gemtuzumab ozogamicin . Source : Vor Biopharma press release , January 14 , 2021 .
Daratumumab and Hyaluronidase-fihj Approved for Light Chain Amyloidosis
The combination of daratumumab and hyaluronidasefihj and bortezomib , cyclophosphamide , and dexamethasone ( D-VCd ) was granted accelerated approval for the treatment of adults with newly diagnosed light chain ( AL ) amyloidosis . This approval makes daratumumab and hyaluronidase-fihj the first FDA-approved treatment for patients with this blood cell disorder .
The application was reviewed under the FDA ’ s Real- Time Oncology Review program , which allows data for certain applications to be reviewed before the applicant formally submits the complete application . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial .
The FDA ’ s decision was based on results from the phase III , randomized , open-label ANDROMEDA study that investigated the safety and efficacy of D-VCd , compared with VCd alone , in 388 patients with newly diagnosed AL amyloidosis . Participants who received D-VCd experienced a complete hematologic response rate more than triple that of patients receiving VCd alone : 42 % versus 13 % ( p < 0.0001 ).
The most common AEs ( occurring in ≥20 % of participants ) included upper respiratory tract infection , diarrhea , peripheral edema , constipation , fatigue , and peripheral sensory neuropathy . Serious AEs occurred in 43 % of patients who received the daratumumab-based combination , the most common of which were pneumonia ( 9 %), cardiac failure ( 8 %), and sepsis ( 5 %). Fatal AEs occurred in 11 % of patients ; these included cardiac arrest ( 4 %), sudden death ( 3 %), cardiac failure ( 3 %), and sepsis ( 1 %).
Based on these cardiac toxicities , the FDA noted that this daratumumab-based combination is not indicated and is not recommended for the treatment of patients with AL amyloidosis who have New York Heart Association Class IIIB or Class IV cardiac disease or Mayo Cardiac Stage IIIB disease outside of controlled clinical trials . Source : Johnson & Johnson press release , January 15 , 2021 .
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