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

Sponsor

Cancer Research UK (Other)

Overall Status

Unknown status

CT.gov ID

NCT00562068

Collaborator

(none)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Small Intestine Cancer	Biological: alemtuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisolone Drug: vincristine sulfate Genetic: polymerase chain reaction Other: flow cytometry Other: laboratory biomarker analysis Other: pharmacological study	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2007

Anticipated Primary Completion Date :

May 1, 2009

Outcome Measures

Primary Outcome Measures

Immediate toxicity (incidence of infusion-related reactions) []
Hematopoietic toxicity (number of cycles of therapy associated with neutrophils < 0.5e9/L or platelets < 50e9/L) []
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) []

Secondary Outcome Measures

Disease response (remission rate [complete response and partial response]) []
Disease outcome (time to progression and overall survival at 2 years from completion of therapy) []
Immune reconstitution (time to recover peripheral blood CD4 count to 0.2 e9/L) []
Relative dose intensity []
Pharmacokinetics assessment of alemtuzumab trough levels before each cycle of treatment []
Epstein-Barr virus copy number (measured retrospectively) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leeds General Infirmary	Leeds	England	United Kingdom	LS1 3EX
2	King's College Hospital	London	England	United Kingdom	SE5 9RS
3	Royal Marsden - London	London	England	United Kingdom	SW3 6JJ
4	Christie Hospital	Manchester	England	United Kingdom	M20 4BX
5	Torbay Hospital	Torbay Devon	England	United Kingdom	TQ2 7AA