Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas

Peripheral T-cell Lymphomas Clinical Trial

— ACCAPELA  

Official title:

Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas: A Multi-centre Phase I and II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00453427
• Other study ID #: CTA-Control-103662
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: March 27, 2007
• Last updated: June 1, 2015
• Start date: September 2006
• Est. completion date: May 2015

Study information

• Verified date: June 2015
• Source: Ontario Clinical Oncology Group (OCOG)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

The primary objectives of this study are to:

1. establish the safety and dose limiting toxicities of combining alemtuzumab with CHOP chemotherapy for patients with newly diagnosed aggressive T-cell lymphomas; and

2. to measure the pharmacokinetics of alemtuzumab used in different subcutaneous doses and schedules.

This will then determine the dose with the highest achievable drug levels with acceptable toxicities worthy of further investigation.

The secondary objectives are to:

1. establish the efficacy of combination alemtuzumab with CHOP chemotherapy; and

2. to measure the effects of combination alemtuzumab with CHOP chemotherapy on T-cell reconstitution and cytomegalovirus (CMV) reactivation.

Description:

Aggressive peripheral T-cell lymphomas account for 10 - 15% of all Non-Hodgkin's Lymphoma (NHL) and present with more adverse prognostic features than aggressive histology B-cell NHL . Correspondingly, they have an overall poorer prognosis than B-cell lymphomas, achieving lower complete response rates, freedom from progression and overall survival with conventional anthracycline-based CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. Fewer than 30% of patients are cured with therapy. New treatments that replicate the improved survivals with chemo-immunotherapy for B-cell lymphomas are needed. Alemtuzumab is a humanized murine antibody that binds to a ubiquitous lymphoid marker CD52 and is efficacious (as monotherapy) in related lymphoproliferative diseases. Combining alemtuzumab with CHOP chemotherapy may improve the response rates and outcomes of patients with this sub-type of NHL. The combination must be first tested in a dose escalation fashion to establish the dosage of the doublet because of the potential for overlapping or exaggerated toxicities.

This prospective, multi-center, open label Phase I-II study will enroll 22-84 patients with newly diagnosed previously untreated aggressive histology peripheral T-cell lymphomas. In the Phase I component, patients will be sequentially enrolled in cohorts of three patients and treated with increasing doses of alemtuzumab administered in combination with standard CHOP chemotherapy. When the maximal tolerated dose is determined, this dose and schedule will then be tested in up to 46 patients using a Simon two stage Phase II design.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 2015
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients aged 18 years of age or older at time of enrollment,

• Histologically proven and centrally reviewed CD52+ T-cell NHL Stages 2-4 including the following nodal and extranodal subtypes:

Nodal:

• Peripheral T-cell lymphoma not otherwise specified (PTL NOS)

• Angioimmunoblastic lymphadenopathy (AILD)

• ALK 1 negative anaplastic large cell NHL

Extranodal:

• Hepatosplenic

• Enteropathy-associated

• Panniculitic

Exclusion Criteria:

• Previous treatment with chemotherapy or radiation with the exception of up to 1 cycle of CHOP chemotherapy.

• Expected survival < 4 months.

• ECOG performance status > 3.

• Inadequate haematologic function (Hb < 85g/L, ANC < 1000/mm3, or platelet count < 75,000/mm3) unless directly attributable to the NHL.

• Inadequate hepatic function (total bilirubin > 35µmol/L, alkaline phosphatase > 2x UL normal, AST/ALT > 2x UL normal)

• Inadequate renal function (serum creatinine > 130µmol/L), unless directly attributable to the NHL.

• Non-measurable or non-evaluable disease, according to criteria of Cheson et al49.

• Geographically inaccessible for follow-up

• Known hypersensitivity to study drugs

• Serious illnesses that may interfere with subject compliance, determination of causality of adverse events or would compromise other protocol objectives.

• Known HIV positivity or other pre-existing immunodeficiency (e.g., post-organ transplant).

• Known CNS involvement with lymphoma (tests to investigate CNS involvement are required only if clinically indicated).

• Pregnant or lactating women.

• Women who are of childbearing potential but are not using effective contraception. Men with reproductive potential who are not using effective contraception.

• Previous malignancy within the last 5 years with the exception of cervical carcinoma in situ or non melanoma skin cancer.

• Nasal natural killer (NK) T-cell NHL

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-cell Lymphomas

Intervention

Drug:
• Alemtuzumab (Campath-1H)
The investigational drug is alemtuzumab (Campath-1H). It is a recombinant humanized monoclonal antibody directed against the CD52 antigen on most (> 95%) normal lymphocytes and T-cell and B-cell lymphomas. Alemtuzumab binds to the CD52 antigen on the cell surface, activating antibody-dependent cellular cytotoxicity, complement binding, apoptosis, cellular opsonization, and anti-tumour T-cell activity.

Locations

Country	Name	City	State
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	London Health Sciences Centre	London	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre, Odette Cancer Centre	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Ontario Clinical Oncology Group (OCOG)	Genzyme, a Sanofi Company, Sunnybrook Health Sciences Centre

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	toxicity		8 cycles of treatment	Yes
Secondary	efficacy		Post cycle 3 and Post cycle 8	Yes
Secondary	tumour response		Post Cycle 3 and Post Cycle 8 Q 6 months in Followup	Yes
Secondary	pharmacokinetic analysis		Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13	Yes
Secondary	immunological monitoring		Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up	No