Alemtuzumab and Combination Chemotherapy in Treating Patients With Stage I, Stage II, Stage III, or Stage IV Peripheral T-Cell Lymphoma

Lymphoma Clinical Trial

Official title:

CHOP-Campath, A Pilot Study of CHOP Plus Campath for the Primary Treatment of ALK-ve Peripheral T Cell Lymphoma [CHOP-CAMPATH]

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00562068
• Other study ID #: CDR0000576439
• Secondary ID: UCL-BRD/05/170EU
• Status: Recruiting
• Phase: Phase 1
• First received: November 20, 2007
• Last updated: August 23, 2013
• Start date: May 2007

Study information

• Verified date: November 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from growing. Giving alemtuzumab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with stage I , stage II , stage III, or stage IV peripheral T-cell lymphoma.

Description:

OBJECTIVES:

Primary

• To determine the feasibility of adding alemtuzumab to standard cyclophosphamide, doxorubicin hydrochloride, vincristine, and oral prednisolone (CHOP) chemotherapy in patients with stage I-IV peripheral T-cell lymphoma (PTCL).

• To assess the side effect profile and early and late toxicities of this regimen in a standard dose-escalation design, and to establish an appropriate dose level for future studies.

Secondary

• To document response rates and disease-free survival of patients treated with this regimen, and to compare these findings with those of historical controls.

• To monitor immune reconstitution after therapy.

• To determine the pharmacokinetics of subcutaneous alemtuzumab when given in combination with CHOP chemotherapy.

• To more clearly define the CD52 expression profile in these tumors and to investigate phenotypic variations in PTCL.

• To document changes (if any) in levels of Epstein-Barr virus copy number by polymerase chain reaction during CHOP-alemtuzumab therapy.

OUTLINE: This is a multicenter, dose escalation of alemtuzumab study.

Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive alemtuzumab subcutaneously (SC) 1-3 times a week for up to 6 doses per course. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline, periodically during study treatment, and after completion of study therapy for pharmacokinetics and other correlative studies to monitor cellular immunity. Blood samples are examined by polymerase chain reaction to detect cytomegalovirus antigen and to monitor Epstein-Barr virus copy number. Samples are also analyzed by flow cytometry to quantify circulating B- and T-cells, NK-cells, monocytes, and dendritic-cells.

After completion of study therapy, patients are followed every 3 months for the first year, every 6 months for the second year, and then yearly thereafter.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of peripheral T-cell lymphoma (PTCL), including the following subtypes:

• PTCL not otherwise specified

• Angioimmunoblastic T-cell lymphoma

• Anaplastic lymphoma kinase-negative anaplastic large cell lymphoma

• Intestinal T-cell lymphoma

• Bulky stage IA and stages IB-IV disease (Ann Arbor staging system)

• Expression of CD52 by the tumor

• Measurable or evaluable disease

• No anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma

• No CNS involvement with non-Hodgkin lymphoma

PATIENT CHARACTERISTICS:

• WHO performance status 0-2

• No presence of other serious, uncontrolled medical conditions

• No significant anthracycline-related cardiac impairment

• LVEF = 50%

• Creatinine = 1.5 mg/dL

• Bilirubin = 2 times normal value unless due to disease

• Not pregnant or nursing

• Fertile patients must use effective barrier contraception during and for 1 month after completion of study treatment

• No previous malignancy except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia

• No positive serology or non-consenting to test for any of the following:

• HIV

• Hepatitis B or C

• Human T-lymphotropic virus type 1 (HTLV-1)

PRIOR CONCURRENT THERAPY:

• No prior cytotoxic chemotherapy

• Prior radiotherapy may be allowed at the trial coordinator's discretion

• Concurrent consolidation radiotherapy may be given at the clinician's discretion

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Small Intestine Cancer

Intervention

Biological:
• alemtuzumab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• prednisolone

• vincristine sulfate

Genetic:
• polymerase chain reaction

Other:
• flow cytometry

• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
United Kingdom	Leeds General Infirmary	Leeds	England
United Kingdom	King's College Hospital	London	England
United Kingdom	Royal Marsden - London	London	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Torbay Hospital	Torbay Devon	England

Sponsors (1)

Lead Sponsor	Collaborator
Cancer Research UK

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immediate toxicity (incidence of infusion-related reactions)			Yes
Primary	Hematopoietic toxicity (number of cycles of therapy associated with neutrophils < 0.5e9/L or platelets < 50e9/L)			Yes
Primary	Incidence of infection (number of days with fever = 38 degrees C, days of intravenous antibiotics, number of inpatient days, number of episodes of cytomegalovirus reactivation)			No
Secondary	Disease response (remission rate [complete response and partial response])			No
Secondary	Disease outcome (time to progression and overall survival at 2 years from completion of therapy)			No
Secondary	Immune reconstitution (time to recover peripheral blood CD4 count to 0.2 e9/L)			No
Secondary	Relative dose intensity			No
Secondary	Pharmacokinetics assessment of alemtuzumab trough levels before each cycle of treatment			No
Secondary	Epstein-Barr virus copy number (measured retrospectively)			No