The Effectiveness of Alemtuzumab Given in Combination With CHOP and ESHAP in Patients Newly Diagnosed With Peripheral T-Cell Lymphoma (PTCL)

Official Title: “A Phase II Study of Alemtuzumab in Combination With CHOP and ESHAP as First-Line Treatment in Peripheral T-Cell Lymphoma”

1. Primary Research Question What are the rates of complete response (CR), partial response (PR), progression free survival (PFS) and overall survival (OS) in adult patients newly diagnosed with Peripheral T-Cell Lymphoma (PTCL) who are treated with alemtuzumab given in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and ESHAP (etoposide, methylprednisolone, cisplatin, cytosine arabinoside) administered as an up-front treatment?

2. Secondary Research Question What is the incidence of life-threatening toxicities (grade 3 and 4, according to WHO criteria, Appendix A) in the patients?

Alemtuzumab (Campath-1H) is a humanized monoclonal antibody that targets CD52, a cell surface protein present at high density on most normal and malignant B and T lymphocytes.

CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) is currently regarded as a standard chemotherapy regimen for patients with newly diagnosed NHL.

ESHAP (etoposide, methylprednisolone, cisplatin, cytosine arabinoside) chemotherapy was invented in 1994. The regimen was aimed to salvage NHL patients who were relapsing or refractory to front-line, mostly doxorubicin-based, chemotherapy.Major toxicities were myelosuppression; 30% of the patients developed febrile neutropenia and was admitted for parenteral antibiotics. Treatment-related deaths, mostly from uncontrolled sepsis, occurred in 4% of the patients. Because of its efficacy and tolerable toxicities, at present, ESHAP is one of the salvage chemotherapy regimens most frequently administered to patients especially prior to autologous stem cell transplantation.

Recently, our unit had reported the efficacy of the combination of standard CHOP chemotherapy and ESHAP and high-dose therapy with autologous stem cell transplantation or rituximab given as upfront therapy in patients newly diagnosed as poor prognosis aggressive NHL (high- and high-intermediate risk groups according to the international index).15,16 According to the previous institutional experience as well as the efficacy of the combination of CHOP and ESHAP in patients with high-risk aggressive lymphoma, we would like therefore to determine the outcome of alemtuzumab given in combination with CHOP and ESHAP in patients newly diagnosed with PTCL, the effectiveness of which has not been known.

Intervention(s) in this Clinical Trial

• Drug: CHOP regimen alternate with ESHAP regimen
  • CHOP alternate with ESHAP is given every 21 days for a total of 6 course.
• Drug: Alemtuzumab
  • Alemtuzumab 30 mg/day is given subcutaneously on day 1-3 of cycle 1-5.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Alemtuzumab combination with CHOP and ESHAP
  • Alemtuzumab 30 mg/day is given subcutaneously on day 1-3 of cycle 1-5. CHOP alternate with ESHAP is given every 21 days for a total of 6 course.

Primary Measures

• The response to treatment and the treatment-related toxicity.
  • Time Frame: 3 years
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Patients must have a diagnosis of one of the following histologic types according to the WHO classification:
• Angioimmunoblastic T-cell lymphoma
• Extranodal NK/T-cell lymphoma, nasal type
• Enteropathy-type T-cell lymphoma
• Hepatosplenic gamma-delta T-cell lymphoma
• Subcutaneous panniculitis-like T-cell lymphoma
• Anaplastic large-cell lymphoma, T/null cell, primary systemic type
• Peripheral T-cell lymphoma, not otherwise characterized
• All biopsy specimens including patients whose diagnosis have been made outside King Chulalongkorn Memorial Hospital will be reviewed by an expert hematopathologist at Department of Pathology, King Chulalongkorn Memorial
• Hospital.
• 2. Newly diagnosed, age 15 - 65 years.
• 3. Complete work up for baseline evaluation and measurement (Appendix B).
• 4. Patient's free written inform consent.

Exclusion Criteria:

• 1. Patients with a known hypersensitivity to murine proteins or to any component of alemtuzumab.
• 2. Patients who have received prior antilymphoma treatment with chemotherapy or radiotherapy.
• 3. Patients with poor performance status (PS; ECOG criteria of 3-4)(Appendix C).
• 4. Serologic evidence of human immunodeficiency virus exposure.
• 5. Patients with history of impaired cardiac status or myocardial infarction.
• 6. Patients with serum creatinine > 1.8 mg/dl, bilirubin > 1.5 times upper limit of normal range, SGOT or SGPT > 3 times upper limit of normal range, unless due to tumor involvement.
• 7. Patients with active uncontrolled infection, active non-malignant gastric or duodenal ulcer, uncontrolled diabetes mellitus or other severe medical conditions which would preclude aggressive cytotoxic chemotherapy.
• 8. Pregnant or lactating women.
• 9. Serious medical or psychiatric illness which prevent informed consent.
• 10. Patients who are likely to lost to follow up (e.g., unwilling or difficult to return, cannot be contacted).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: King Chulalongkorn Memorial Hospital Other

Overall Clinical Trial Officials and Contacts

Tanin Intragumtornchai, M.D. Principal Investigator Division of Hematology and Stem Cell Transplant, Department of Medicine, Faculty of Medicine, Chulalongkorn University  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00930605

Study ID Number: TH011001

ClinicalTrials.gov Identifier: NCT00930605

Health Authority: Thailand: Food and Drug Administration