- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00453427
Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas (ACCAPELA)
Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas: A Multi-centre Phase I and II Study
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
British Columbia
-
Vancouver, British Columbia, Canada, V6Z 1Y6
- St. Paul's Hospital
-
-
Ontario
-
Hamilton, Ontario, Canada, L8V 5C2
- Juravinski Cancer Centre
-
London, Ontario, Canada, N6A 4G5
- London Health Sciences Centre
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital
-
Toronto, Ontario, Canada, M4N 3M5
- Sunnybrook Health Sciences Centre, Odette Cancer Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
toxicity
Time Frame: 8 cycles of treatment
|
8 cycles of treatment
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
efficacy
Time Frame: Post cycle 3 and Post cycle 8
|
Post cycle 3 and Post cycle 8
|
tumour response
Time Frame: Post Cycle 3 and Post Cycle 8 Q 6 months in Followup
|
Post Cycle 3 and Post Cycle 8 Q 6 months in Followup
|
pharmacokinetic analysis
Time Frame: Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13
|
Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13
|
immunological monitoring
Time Frame: Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up
|
Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up
|
Collaborators and Investigators
Investigators
- Principal Investigator: Rena Buckstein, MD, Sunnybrook Health Sciences Centre, Odette Cancer Centre
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CTA-Control-103662
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Peripheral T-cell Lymphomas
-
Stanford UniversityNational Institutes of Health (NIH); AmgenCompletedLymphoma, Non-Hodgkin | Lymphomas: Non-Hodgkin | Lymphomas: Non-Hodgkin Peripheral T-Cell | Lymphomas: Non-Hodgkin Cutaneous Lymphoma | Lymphomas: Non-Hodgkin Diffuse Large B-Cell | Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell | Lymphomas: Non-Hodgkin Mantle Cell | Lymphomas: Non-Hodgkin Marginal... and other conditionsUnited States
-
National Health Research Institutes, TaiwanNational Taiwan University Hospital; China Medical University Hospital; Chang... and other collaboratorsNot yet recruitingPeripheral T-cell Lymphomas (PTCL)Taiwan
-
Nanjing NingQi Medicine Science and Technology...Jiangsu Cancer Institute & HospitalUnknownPeripheral T-cell LymphomasChina
-
National Cancer Institute (NCI)RecruitingImmune System Diseases | Lymphoproliferative Disorders | Peripheral T-cell LymphomasUnited States
-
Samsung Medical CenterJanssen Medical AffairsCompletedNon-Hodgkin Lymphoma | Peripheral T-Cell LymphomasKorea, Republic of
-
Fondazione Italiana Linfomi - ETSActive, not recruitingPeripheral T-cell Lymphomas (PTCL) | PTCL-NOS | Angioimmunoblastic T-cell Lymphoma (AITL) | ALK- Anaplastic Large Cell Lymphoma (ALCL) | Nodal Peripheral T-Cell Lymphoma of T Follicular Helper Cell OriginItaly
-
University of Alabama at BirminghamTerminatedAnaplastic Large Cell Lymphoma | Angioimmunoblastic T-cell Lymphoma | Peripheral T-cell Lymphomas | Adult T-cell Leukemia | Adult T-cell Lymphoma | Peripheral T-cell Lymphoma Unspecified | T/Null Cell Systemic Type | Cutaneous t-Cell Lymphoma With Nodal/Visceral DiseaseUnited States
-
Memorial Sloan Kettering Cancer CenterActive, not recruitingT-cell Large Granular Lymphocyte Leukemia | T-cell Lymphomas | T-cell Prolymphocytic Leukemia | NK-Cell LymphomasUnited States
-
Memorial Sloan Kettering Cancer CenterDana-Farber Cancer Institute; Stanford UniversityActive, not recruitingLymphoma | Relapsed/Refractory T-cell LymphomasUnited States
-
Assistance Publique - Hôpitaux de ParisActive, not recruitingEpidermotropic T-cell LymphomasFrance
Clinical Trials on Alemtuzumab (Campath-1H)
-
M.D. Anderson Cancer CenterWithdrawnLymphoma | Hodgkin's Disease
-
Northwestern UniversityGenzyme, a Sanofi Company; Millennium Pharmaceuticals, Inc.Completed
-
M.D. Anderson Cancer CenterLeudositeTerminatedLymphoma, B-Cell | Lymphoma, T-Cell | Lymphoma, Low-Grade | Leukemia, Lymphocytic, Acute | Leukemia, Lymphocytic, ChronicUnited States
-
Chronic Lymphocytic Leukemia Research ConsortiumBayerUnknownB-Cell Chronic Lymphocytic LeukemiaUnited States
-
M.D. Anderson Cancer CenterTerminated
-
M.D. Anderson Cancer CenterBerlex Laboratories, Inc.CompletedChronic Lymphocytic LeukemiaUnited States
-
University of Wisconsin, MadisonWithdrawnNew Onset Type 1 Diabetes MellitusUnited States
-
Genzyme, a Sanofi CompanyCompletedLeukemia, Lymphocytic, Chronic, B-CellJapan
-
University of Wisconsin, MadisonTerminatedDisorder Related to Renal TransplantationUnited States
-
Assistance Publique - Hôpitaux de ParisCompletedAcute Lymphocytic LeukemiaFrance