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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Sunnybrook Health Sciences Centre
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier:
NCT00453427
First received: March 27, 2007
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Peripheral T-cell Lymphomas
Drug: Alemtuzumab (Campath-1H)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Alemtuzumab and CHOP Chemotherapy for Aggressive Histological Peripheral T-Cell Lymphomas: A Multi-centre Phase I and II Study

Resource links provided by NLM:


Further study details as provided by Ontario Clinical Oncology Group (OCOG):

Primary Outcome Measures:
  • toxicity [ Time Frame: 8 cycles of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • efficacy [ Time Frame: Post cycle 3 and Post cycle 8 ] [ Designated as safety issue: Yes ]
  • tumour response [ Time Frame: Post Cycle 3 and Post Cycle 8 Q 6 months in Followup ] [ Designated as safety issue: Yes ]
  • pharmacokinetic analysis [ Time Frame: Day 1 of 8 Cycles of treatment and Post Last Dose on Day 3,6,10,13 ] [ Designated as safety issue: Yes ]
  • immunological monitoring [ Time Frame: Baseline Day 1 On Treatment Day 1 Cycle 4 and Cycle 8 and 6 months Follow-up ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: September 2006
Estimated Study Completion Date: June 2016
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00453427

Locations
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Health Sciences Centre
London, Ontario, Canada, N6A 4G5
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sunnybrook Health Sciences Centre, Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Sponsors and Collaborators
Ontario Clinical Oncology Group (OCOG)
Sunnybrook Health Sciences Centre
Genzyme, a Sanofi Company
Investigators
Principal Investigator: Rena Buckstein, MD Sunnybrook Health Sciences Centre, Odette Cancer Centre
  More Information

No publications provided

Responsible Party: Ontario Clinical Oncology Group (OCOG)
ClinicalTrials.gov Identifier: NCT00453427     History of Changes
Other Study ID Numbers: CTA-Control-103662
Study First Received: March 27, 2007
Last Updated: February 24, 2014
Health Authority: Canada: Health Canada

Keywords provided by Ontario Clinical Oncology Group (OCOG):
PTL NOS
AILD
NHL
CHOP

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Alemtuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014