SAN FRANCISCO--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced that data were presented from a phase 1b/2 study of ISTODAX® (romidepsin) combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in patients with peripheral t-cell lymphoma were presented during the 56th American Society of Hematology annual meeting.
In the phase Ib and phase II portions of this study, presented by Jehan Dupuis, M.D. (from the Lymphoma Study Association or LYSA), a total of 37 patients were treated with romidepsin at varying doses plus CHOP. Based on results from phase I (n=18), the recommended dose of romidepsin for the phase II portion was 12 mg/m2 (n= 19).
Two patients had an early cardiac event (myocardial infarction) and were excluded from the efficacy analysis. A third patient had a cardiac event (acute cardiac failure) during the first cycle and continued on CHOP alone.
Fifty-one percent of patients (18/35) in the study achieved a complete response, with 17% (6/35) achieving a partial response and 26% (9/35) having progressive disease. With a median follow-up of 30 months, median PFS is 21.3 months with 21 patients having progressed.
The most common grade 3-4 hematologic adverse events were neutropenia (85%), thrombocytopenia (35%) and anemia (8%).
The most common grade 3-4 non-hematologic adverse events (AE) were febrile neutropenia (19%), general physical health deterioration (13%), hypophosphatemia (10.8%) and vomiting (10%). There were no deaths attributable to toxicity.
“Based on this study, the combination of romidepsin and CHOP shows potential for the treatment of patients with PTCL, and supports further study through the phase III comparison of RO-CHOP and CHOP alone in this area of disease,” said Bertrand Coiffier, M.D., Ph.D., lead investigator of the study (Richard Delarue M.D. is co investigator).
The combination of ISTODAX® and CHOP is not approved for any indication in any country.
About ISTODAX®
ISTODAX® (romidepsin) for injection is indicated for treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.
ISTODAX® (romidepsin) for injection is indicated for treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
Important Safety Information
WARNINGS AND PRECAUTIONS
• Myelosuppression: ISTODAX® (romidepsin) can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts regularly during treatment with ISTODAX; interrupt and/or modify the dose as necessary
• Infections: Fatal and serious infections, including pneumonia, sepsis, and viral reactivation, including Epstein Barr and hepatitis B viruses, have been reported during and within 30 days after treatment with ISTODAX in clinical trials. The risk of life threatening infections may be greater in patients with a history of prior treatment with monoclonal antibodies directed against lymphocyte antigens and in patients with disease involvement of the bone marrow. Reactivation of Epstein Barr viral infection led to liver failure. Consider monitoring for reactivation and antiviral prophylaxis in patients with evidence of prior hepatitis B infection. Ganciclovir prophylaxis failed to prevent Epstein Barr viral reactivation in one case
• Electrocardiographic (ECG) changes: ECG changes have been observed with ISTODAX. In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, consider cardiovascular monitoring of ECGs at baseline and periodically during treatment. Confirm that potassium and magnesium levels are within the normal range before administration of ISTODAX
• Tumor lysis syndrome: TLS (Tumor lysis syndrome) has been reported during treatment with ISTODAX. Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and managed as appropriate
• Embryo-fetal toxicity: ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women of potential hazard to the fetus and to avoid pregnancy while receiving ISTODAX
ADVERSE REACTIONS
Peripheral T-Cell Lymphoma
The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 3 (N=131) were thrombocytopenia (24%), neutropenia (20%), anemia (11%), asthenia/fatigue (8%), and leukopenia (6%), and in Study 4 (N=47) were neutropenia (47%), leukopenia (45%), thrombocytopenia (36%), anemia (28%), asthenia/fatigue (19%), pyrexia (17%), vomiting (9%), and nausea (6%).
Infections were the most common type of serious adverse event reported in Study 3 (N=131) and Study 4 (N=47). In Study 3, 26 patients (20%) experienced a serious infection, including 6 patients (5%) with serious treatment-related infections. In Study 4, 11 patients (23%) experienced a serious infection, including 8 patients (17%) with serious treatment-related infections.
The most common adverse reactions regardless of causality in Study 3 (N=131) were nausea (59%), asthenia/fatigue (55%), thrombocytopenia (41%), vomiting (39%), diarrhea (36%), and pyrexia (35%), and in Study 4 (N=47) were asthenia/fatigue (77%), nausea (75%), thrombocytopenia (72%), neutropenia (66%), anemia (62%), leukopenia (55%), pyrexia (47%), anorexia (45%), vomiting (40%), constipation (40%), and diarrhea (36%).
Cutaneous T-Cell Lymphoma
The most common Grade 3/4 adverse reactions (>5%) regardless of causality in Study 1 (N=102) were infections (11%) and asthenia/fatigue (8%), and in Study 2 (N=83) were lymphopenia (37%), infections (33%), neutropenia (27%), leukopenia (22%), anemia (16%), asthenia/fatigue (14%), thrombocytopenia (14%), hypophosphatemia (10%), vomiting (10%), dermatitis/exfoliative dermatitis (8%), hypermagnesemia (8%), hyperuricemia (8%), hypocalcemia (6%), nausea (6%), and pruritus (6%).
Infections were the most common type of serious adverse event reported in both Study 1 (N=102) and Study 2 (N=83) with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a serious infection.
The most common adverse reactions regardless of causality in Study 1 (N=102) were nausea (56%), asthenia/fatigue (53%), infections (46%), vomiting (34%), and anorexia (23%), and in Study 2 (N=83) were nausea (86%), asthenia/fatigue (77%), anemia (72%), thrombocytopenia (65%), ECG ST-T wave changes (63%), neutropenia (57%), lymphopenia (57%), infections (54%), anorexia (54%), vomiting (52%), hypocalcemia (52%), hyperglycemia (51%), hypoalbuminemia (48%), leukopenia (46%), dysgeusia (40%), and constipation (39%).
DRUG INTERACTIONS
• Monitor more frequently prothrombin time and International Normalized Ratio in patients concurrently administered ISTODAX and warfarin or coumarin derivatives
• Romidepsin is metabolized by CYP3A4
º Monitor patients for toxicity related to increased romidepsin exposure and follow dose modifications for toxicity when ISTODAX is initially co-administered with strong CYP3A4 inhibitors
º Avoid co-administration of ISTODAX (romidepsin) with rifampin and other potent inducers of CYP3A4
• Exercise caution with concomitant use of ISTODAX and P-glycoprotein (P-gp, ABCB1) inhibitors
USE IN SPECIFIC POPULATIONS
• Pregnancy Category D: If this drug is used during pregnancy, or if the patient becomes pregnant while taking ISTODAX, the patient should be apprised of the potential hazard to the fetus
• Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother
• Patients with moderate and severe hepatic impairment and/or patients with end-stage renal disease should be treated with caution
Please see Full Prescribing Information.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow us on Twitter @Celgene as well.
Forward-Looking Statements
This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans,” “will,” “outlook” and similar expressions. Forward-looking statements are based on management’s current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.
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