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

Primary Purpose

Peripheral T-cell Lymphomas

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Alemtuzumab (Campath-1H)

About this trial

This is an interventional treatment trial for Peripheral T-cell Lymphomas focused on measuring PTL NOS, AILD, NHL, CHOP

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

St. Paul's Hospital
Juravinski Cancer Centre
London Health Sciences Centre
Sunnybrook Health Sciences Centre, Odette Cancer Centre
Princess Margaret Hospital

Outcomes

Primary Outcome Measures

toxicity

Secondary Outcome Measures

efficacy

tumour response

pharmacokinetic analysis

immunological monitoring

Full Information

NCT ID

NCT00453427

First Posted

March 27, 2007

Last Updated

June 1, 2015

Sponsor

Ontario Clinical Oncology Group (OCOG)

Collaborators

Sunnybrook Health Sciences Centre, Genzyme, a Sanofi Company

1. Study Identification

Unique Protocol Identification Number

NCT00453427

Brief Title

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

Acronym

ACCAPELA

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2015

Overall Recruitment Status

Completed

Study Start Date

September 2006 (undefined)

Primary Completion Date

June 2013 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Ontario Clinical Oncology Group (OCOG)

Collaborators

Sunnybrook Health Sciences Centre, Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objectives of this study are to: establish the safety and dose limiting toxicities of combining alemtuzumab with CHOP chemotherapy for patients with newly diagnosed aggressive T-cell lymphomas; and 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: establish the efficacy of combination alemtuzumab with CHOP chemotherapy; and to measure the effects of combination alemtuzumab with CHOP chemotherapy on T-cell reconstitution and cytomegalovirus (CMV) reactivation.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peripheral T-cell Lymphomas

Keywords

PTL NOS, AILD, NHL, CHOP

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

Alemtuzumab (Campath-1H)

Intervention Description

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.

Primary Outcome Measure Information:

Title

toxicity

Time Frame

8 cycles of treatment

Secondary Outcome Measure Information:

Title

efficacy

Time Frame

Post cycle 3 and Post cycle 8

Title

tumour response

Time Frame

Post Cycle 3 and Post Cycle 8 Q 6 months in Followup

Title

pharmacokinetic analysis

Time Frame

Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13

Title

immunological monitoring

Time Frame

Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rena Buckstein, MD

Organizational Affiliation

Sunnybrook Health Sciences Centre, Odette Cancer Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

St. Paul's Hospital

City

Vancouver

State/Province

British Columbia

ZIP/Postal Code

V6Z 1Y6

Country

Canada

Facility Name

Juravinski Cancer Centre

City

Hamilton

State/Province

Ontario

ZIP/Postal Code

L8V 5C2

Country

Canada

Facility Name

London Health Sciences Centre

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 4G5

Country

Canada

Facility Name

Sunnybrook Health Sciences Centre, Odette Cancer Centre

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4N 3M5

Country

Canada

Facility Name

Princess Margaret Hospital

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

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

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