ACT-1 trial in PTCL, (alemtuzumab + CHOP-14) preliminary findings: acceptable safety, 67% ORR in total patient population (57)

Program: Oral and Poster Abstracts
Type: Oral
Session: 624. Lymphoma - Therapy with Biologic Agents, excluding Pre-Clinical Models: Novel Agents and Targeted Therapies

Sunday, December 9, 2012: 12:30 PM

Sidney Marcus Auditorium, Level 4, Building A (Georgia World Congress Center)

Francesco d'Amore¹, Sirpa Leppä, Professor², Maria Gomes da Silva^3*, Thomas Relander^4*, Peter De Nully Brown⁵, Eckhart Weidmann^6*, Grete Fossum Lauritzsen^7*, Antonio Pezzutto^8*, Achiel Van Hoof⁹, Michel van Gelder^10*, Jeanette K Doorduijn, MD, PhD^11,12,13, Ka Lung Wu, MD, PhD¹⁴, J.C. Kluin-Nelemans¹⁵, P.J. Lugtenburg¹⁶, Milada Jankovska^17*, Mats Merup^18*, Unn-Merete Fagerli^19*, Jan Walewski²⁰, Hans Hagberg^21*, Jose Mario Mariz²², Per Boye Hansen^23*, Thomas Nösslinger^24*, Ann Janssens^25*, Lena Brandefors^26*, Hilde Demuynck²⁷, Martyn Ronald Schaafsma²⁸, Ilse Christiansen²⁹, David Salek^30*, Sirkku Jyrkkiö^31*, Vit Prochazka^32*, Josee Zijlstra^33*, L. Böhmer^34*, Richard Greil, MD³⁵, Wendy Stevens^36*, Rob Fijnheer^37*, Marinus van Marwijk Kooy^38*, Matthias Grube^39*, Georg Hopfinger^40*, Eric Van den Neste^41*, Esa Jantunen^42*, Lorenz Trümper^43*, Gerald Wulf⁴³, Bettina Altmann^44*, Marita Ziepert^44*, Markus Loeffler^44* and Helle Toldbod^1*

¹Department of Hematology, Aarhus University Hospital, Aarhus, Denmark
²Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
³Portuguese Institute of Oncology, Lisbon, Portugal
⁴Department of Oncology, Lund University Hospital, Lund, Sweden
⁵Dept. of Hematology, Rigshospitalet, Copenhagen, Denmark
⁶Department of Hematology and Oncology, Krankenhaus Nordwest, Frankfurt, Germany
⁷Oncology, Oslo University Hospital, Norway
⁸Hematology/Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany
⁹University Hospital St-Jan, Brugge, Belgium
¹⁰Hematology, Maastricht University Medical Center, Maastricht, Netherlands
¹¹Department of Hematology, Erasmus MC, Rotterdam, Netherlands
¹²hematology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands
¹³Hematology, Erasmus MC University Medical Center/Daniel den Hoed Cancer Center, Rotterdam, Netherlands
¹⁴Hematology, ZNA Stuivenberg, Antwerp, Belgium
¹⁵Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands
¹⁶Dept. of Hematology, Erasmus MC, Rotterdam, Netherlands
¹⁷Department of Clinical Hematology, Third Faculty of Medicine, Charles University Hospital Kralovske Vinohrady, Prague, Czech Republic
¹⁸Department of Hematology, Karolinska University Hospital, Stockholm, Sweden
¹⁹Oncology, St. Olavs University Hospital, Norway
²⁰Department of Lymphoproliferative Diseases, Maria Sklodowska-Curie Memorial Institute and Cancer Center, Warsaw, Poland
²¹Department of Oncology, Uppsala University Hospital, Uppsala, Sweden
²²Hematology, IPO Porto, Porto, Portugal
²³Hematology, Herlev University Hospital, Denmark
²⁴3rd Med. Dept. for Hem. & Onc., Hanusch Hospital, Vienna, Austria
²⁵Department of Hematology, University Hospitals Leuven, Leuven, Belgium
²⁶Dept of Medicine, Sunderby Hospital, Luleå, Sweden
²⁷Department of Haematology, Heilig Hartziekenhuis Roeselare-Menen, Roeselare, Belgium
²⁸Medisch Spectrum Twente, Enschede, Netherlands
²⁹Department of Hematology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark
³⁰Dept Haemato-oncology, University Hospital Brno, Brno, Czech Republic
³¹Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
³²Department of Hematology, University Hospital Olomouc, Olomouc, Czech Republic
³³Dept. of Hematology, VU University Medical Center, Amsterdam, Netherlands
³⁴Dep. oF Hematology, Haga Ziekenhuis, Den Haag
³⁵IIIrd Medical Department with Hematology and MEdical Oncology, Paracelsus Medical University Salzburg, Salzburg, Austria
³⁶Dep. Hematology, University Medical Center St. Radboud, Nijmegen
³⁷Department of Internal Medicine, Meander Medical Center, Amersfoort, Netherlands
³⁸Department of Internal Medicine, Isala Klinieken, Zwolle, Netherlands
³⁹Department of Hematology and Oncology, University Clinic Regensburg, Regensburg, Germany
⁴⁰Department of Internal Medicine III, University Hospital Salzburg, Salzburg, Austria
⁴¹Hematology Department, Cliniques universitaires UCL Saint-Luc, Brussels, Belgium
⁴²Department of Medicine, Kuopio University Hospital, Kuopio, Finland
⁴³Department of Hematology and Oncology, Georg-August-Universitaet Goettingen, Göttingen, Germany
⁴⁴Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany

Background

The ACT trial (ACT-1, younger patients aged 18-60 yrs and ACT-2, elderly patients aged >60 yrs) is the first international randomized phase III trial in newly diagnosed primary systemic peripheral T-cell lymphoma (PTCL). It tests, in both younger and elderly patients, the efficacy of the addition of alemtuzumab (ALZ) to 6 courses of bi-weekly CHOP followed, only in younger patients (ACT-1), by high-dose therapy with autologous stem cell rescue.  A dose reduction amendment tapering the cumulative ALZ dose from 360 mg (30 mg on days 1 and 2 of  CHOP courses 1-6) to 120 mg (30 mg on day 1 of CHOP courses 1-4), respectively, was introduced early on due to two cases of systemic fungal infection (Blood 2011,118;4110). To date, the trial has accrued a total of 186 patients (ACT-1 n=98; ACT-2 n=88).

Aim

Here, we present the results from the first interim efficacy and safety analysis of the ACT-1 trial based on the first 68 randomized patients.

Results

Of the 68 patients, 63 had a complete set of treatment data. The median follow-up was 15 months (range 0.5-42 months). Thirty-two patients belonged to the experimental arm (exp) and 31 to the standard arm (std). Of the 32 patients treated according to exp, 4 received the higher dose of ALZ and 28 the lower. Treatment arms were well balanced with regard to main prognostic features such as age (std: median 53 yrs, range 21-60 yrs; exp: median 50 yrs, range 22-64 yrs; p=0.705), IPI subgroups (std: low 10%, low-intermediate 51%, intermediate-high 29%, high 10%; exp: low 12%, low-intermediate 44%, intermediate-high 19%, high 25%; p=0.392), advanced clinical stage (std: stage III-IV 94%; exp: 97%; p=0.613), performance status ECOG>1 (std: 23%; exp: 28%; p=0.613), elevated LDH (std: 68%; exp: 69%; p=0.932), presence of B-symptoms (std: 68%; exp: 75%; p=0.524), bulky disease (std: 13%; exp: 13%; p=1.0) and bone marrow involvement (std: 39%; exp: 31%; p=0.535). Histological subtypes were also similarly distributed among both treatment arms (std: PTCL-NOS 55%, AILT 23%, other 22%; exp: PTCL-NOS 56%, AILT 28%, other 16%). No cases of anaplastic large cell PTCL (regardless of ALK-protein status) were included. Neither of the treatment cohorts showed significant treatment delay. The median duration of chemotherapy (calculated for 5 bi-weekly cycles of an expected cumulative duration of 70 days) for non-ALZ vs. ALZ-treated patients was 73 vs. 81 days, respectively. No suspected unexpected serious adverse reactions (SUSARs) were reported. Grade 4 leucopenia was more frequent in ALZ-treated patients (std: 24%, exp: 69%; p=0,001), whereas grade 3-4 anemia and grade 3-4 thrombocytopenia were not significantly different between treatment arms (anemia, std: 19%, exp: 31%; p=0,278; thrombocytopenia, std: 20%, exp: 12%, p=0,682) . Non-hematological toxicity unrelated to infectious complications was mild and had a similar frequency in both arms. The number of serious adverse events (SAEs) per patient was 0.86 for patients treated at post-amendment ALZ dose levels, representing a significant reduction compared to the pre-amendment value (3.25), and 0.46 for patients treated in the control arm (p=0.002). The frequency of bacterial and fungal infections (grade ≥3) was similar in both treatment arms. ALZ treated patients had more viral events (9/32; 28% vs. 3/31; 10%), mainly (6 out of 9) consisting of asymptomatic cytomegalovirus reactivations. The overall (non-arm specific) 1-year event-free survival (primary end-point), progression-free survival and overall survival were 55% (95% CI: 42%-67%), 54% (95% CI: 42%-67%) and 78% (95% CI: 67%-88%), respectively.

Conclusion

The safety profile of the current standard and experimental treatment schedules, as well as the interim outcome results, support a continuation of the trial. A final analysis will be performed in Q2 2015.

Disclosures: d'Amore: Sanofi: Research Funding; Amgen: Research Funding. Jantunen: Genzyme: Has participated in EU Leadership meeting organized by Genzyme as well as Medical Advisory Board meeting organized by Genzyme Other, Honoraria.