Cutaneous T-Cell Lymphoma
June 12, 2017
Takeda Pharmaceutical and Seattle Genetics reported results of a phase III trial of Adcetris (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). ALCANZA is a randomized, open-label study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of the standard of care therapies methotrexate or bexarotene. The objective response lasting at least four months (ORR4), as assessed by Global Response Score, was 56.3% in the ADCETRIS arm compared to 12.5% in the control arm (p=<0.0001). Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the Adcetris arm. The safety profile associated with Adcetris from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia. Based on the study results, Takeda plans to begin to submit data from the ALCANZA trial to regulatory agencies in its territories in 2017. The FDA granted Breakthrough Therapy Designation to ADCETRIS for the treatment of the most common subtypes of CTCL, mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Seattle Genetics plans to submit these data as part of a supplemental Biologics License Application to the FDA in mid-2017. The ALCANZA trial received a Special Protocol Assessment (SPA) agreement from the FDA and scientific advice from the EMA.
August 8, 2016
Seattle Genetics and Takeda Pharmaceutical reported phase III results of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). The ALCANZA trial is a randomized, open-label study designed to evaluate single-agent ADCETRIS versus a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in patients with CD30-expressing CTCL, including those with primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). The primary endpoint is ORR4 as assessed by Global Response Score in the ADCETRIS arm compared to the control arm. Key secondary endpoints are complete response rate, progression-free survival and reduction in the burden of symptoms during treatment. The clinical trial enrolled 131 patients at 50 sites globally. The results of the ALCANZA trial demonstrated that treatment with ADCETRIS resulted in a highly statistically significant improvement in the ORR4 versus the control arm as assessed by an independent review committee (p<0.0001). The ORR4 was 56.3% in the ADCETRIS arm compared to 12.5% in the control arm. The key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment, were all highly statistically significant in favor of the ADCETRIS arm. The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. ADCETRIS received Orphan Drug designation from the FDA for the treatment of mycosis fungoides, which is the most common type of CTCL. ADCETRIS also received Orphan Drug designation from the European Commission for CTCL, including subtypes primary cutaneous anaplastic large cell lymphoma and mycosis fungoides.
December 21, 2015
Spectrum Pharmaceuticals has reported results of a phase I combination trial of belinostat (Beleodaq) with the CHOP (cyclophosphamide, hydroxyl-doxorubicin, Oncovin and Prednisone) chemotherapy regimen as first-line treatment for newly diagnosed peripheral T-cell lymphoma (PTCL). Oncovin is a brand name for vincristine. The open-label, two-part trial enrolled a total of 23 patients. Eleven were enrolled in part A, the dose-escalation phase, to determine the study’s primary endpoint, the maximum tolerated dose (MTD). Part B of the study, the expansion phase, enrolled 12 additional patients at that dose level. The MTD of belinostat was established at 1,000mg/m2 IV infusion on days one through five (the recommended single agent dose) when combined with the CHOP regimen, with each component given at its full recommended dose. Secondary endpoints included safety, tolerability, Objective Response Rate (ORR: complete response + partial response) and pharmacokinetics. Results showed an ORR of 86% with the belinostat and CHOP combination, based on 21 evaluable patients (18/21), with the vast majority, 67%, achieving a complete response (14/21), and 19% achieving a partial response (4/21). In addition, the belinostat and CHOP combination was shown to have an acceptable safety profile with no new or unexpected toxicities. The most common (>10%) grade three/four hematologic adverse events (AEs) reported with Bel-CHOP were as expected: neutrophil count decreased (30%), anemia (22%), neutropenia (22%), white blood cell (WBC) count decreased (22%), febrile neutropenia (17%) and lymphocyte count decreased (17%). No grade three/four non-hematologic AEs >10% were reported. No patient discontinued therapy due to AEs. One patient died as a result of disease progression during the study. Beleodaq is a histone deacetylase (HDAC) inhibitor that received accelerated approval by the FDA for the treatment of relapsed or refractory PTCL in July 2014.
February 3, 2014
Janssen has issued positive results of a
phase II study of siltuximab for the treatment
of Multicentric Castleman’s Disease
(MCD) in subjects who are HIV-negative and
human herpes virus-8 (HHV-8)-negative. The
multi-national, randomized, double-blind,
placebo-controlled study involved 79 subjects
randomized 2:1 to receive either siltuximab
plus best supportive care (BSC) or placebo plus
BSC until protocol-defined treatment failure,
after which patients taking the placebo could
cross over to un-blinded siltuximab. Half of
the patients on placebo (13 out of 26) crossed
over to siltuximab. The study found more
than one-third of patients in the siltuximab
arm had a durable tumor and symptomatic
response to treatment, compared to none of
the patients who received placebo plus BSC
(34% v. 0%). In looking at the response rate to
treat MCD-related symptoms, 25% of patients
who received siltuximab plus BSC had durable
complete symptom resolution, defined as
100% reduction of baseline overall symptom
scores for at least 18 weeks, compared to none
of the patients who received placebo plus BSC.
These data supported the recent regulatory
filings of siltuximab in the U.S. and E.U.
May 21, 2012
Seattle Genetics reported interim results from a phase II trial of Adcetris for the treatment of relapsed cutaneous T-cell lymphoma (CTCL). The study enrolled 17 patients with mycosis fungoides or Sezary syndrome who had previously received other therapies. The primary endpoint of the trial is clinical response rate. Twelve of 16 evaluable patients (75%) achieved a partial remission. In addition, median CD30 expression on lymphoid cells in biopsies of skin lesions was 15%. At week 25, 68% of patients maintained response, although a median duration of response had not yet been reached. The most common adverse events thus far are peripheral neuropathy, fatigue, decreased appetite and generalized skin eruption. There was one patient death due to respiratory failure presumably secondary to pneumonia. Seattle Genetics will continue the phase II study.
January 5, 2004
Genmab reported positive interim results from two phase II trials investigating HuMax-CD4 for the treatment of cutaneous T-cell lymphoma (CTCL). Results showed 55% of the early stage and 38% of the advanced stage subjects achieved at least a partial response, using the Physician's Global Assessment (PGA) scale. The PGA is a comparison of baseline conditions that grades all cancerous lesions from 0 to 6. Data showed that 9% of the early stage and 23% of the advanced stage patients achieved a minor response. In addition, pruritus was improved in 82% of early stage patients and 69% of advanced stage patients. The study enrolled 11 early stage and 13 advanced stage subjects with CTCL.
Introgen reported data from a phase I clinical trial indicating that INGN 241, an MDA-7 gene therapeutic, was well tolerated and was clinically active in subjects with solid tumors. Results showed that the MDA-7 protein was detectable 4 cm away from the injection site. Intratumoral injection of INGN 241 produced protein both in local and diffusible forms. This observation was correlated with apoptosis at the external edge of the tumor that was injected. Results were reported at the 12th Annual International Conference on Gene Therapy of Cancer in San Diego. INGN 241 is currently in phase II clinical trials for the treatment of solid tumors.
Millennium Pharmaceuticals announced positive preliminary results from a phase I/II, investigator-initiated trial with Velcade (bortezomib) in combination with thalidomide with dexamethasone for the treatment of advanced stage multiple myeloma. Of the 56 subjects who are currently enrolled in the trial, 96% received prior autotransplant and 81% received prior thalidomide. Investigators reported that responses were observed in subjects who had previously received thalidomide treatment, and more than 20% of subjects achieved a complete or near complete response. Adverse events included gastrointestinal events, fatigue, peripheral neuropathy and hematologic toxicities. Results were reported at the 45th Annual Meeting of the American Society of Hematology (ASH) in San Diego.
February 18, 2003
Abbott Laboratories reported negative preliminary results from a phase III trial investigating atrasentan (ABT-627), an endothelin-blocking protein for the treatment of metastatic prostate cancer. Results showed that the study did not meet its primary endpoint, time-to-disease progression. The endpoint was defined as the need for pain medication, chemotherapy, radiation, and the progression of cancer in bone. The study showed subject dropout rates that were similar to placebo and were lower than in previous studies. Data showed a statistically significant improvement in prostate-specific antigen (PSA) levels compared to placebo (175 ng/ml vs. 257 ng/ml) and improvements in skeletal progression markers. The double blind, placebo-controlled, multinational study enrolled 810 subjects and was designed to examine the effects of atrasentan in men with advanced metastatic hormone-refractory prostate cancer. The company will continue the development of atrasentan in non-metastatic prostate cancer and other cancers.
Transgene reported positive results from two phase I trials investigating their gene therapy products, Adeno Interferon gamma (Ad-IFNg) and Adeno Interleukin-2 (Ad-IL2) for the treatment of various cancers. Both products showed positive results in gene transfer efficiency and cytokine expression. The results also showed positive clinical responses in tumor regression and stabilizations in cutaneous lymphoma subjects treated with Ad-IFNg. The Ad-IFNg trial enrolled 20 subjects with metastatic melanoma or other advanced solid tumors. The Ad-IL2 trial enrolled nine subjects with primary cutaneous T-cell lymphoma and multilesional cutaneous B-cell lymphoma. Treatments were well tolerated in both studies with only mild injection site reactions reported.