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Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00069238
First Posted: September 18, 2003
Last Update Posted: October 18, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Wyndham Wilson, M.D., National Institutes of Health Clinical Center (CC)
  Purpose

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkins lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkin s lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objectives:

Determine the toxicity of Alemtuzumab and etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy in untreated cluster of differentiation 52 (CD52)-expressing T and natural killer (NK) lymphoid malignancies.

Determine the maximum tolerated dose of Alemtuzumab administered in combination with EPOCH chemotherapy.

Determine in a preliminary fashion the anti-tumor activity of the combination of Alemtuzumab and EPOCH chemotherapy.

Eligibility:

CD52-expressing lymphoid malignancy.

Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Adequate organ function, unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart. failure within the past year.

Human immunodeficiency virus (HIV) negative.

Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in a preliminary fashion the antitumor activity of the combination with Dose-Adjusted EPOCH.

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each. Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed by dose-adjusted EPOCH chemotherapy days 1-5.


Condition Intervention Phase
Lymphoma, T-Cell Lymphoma, Extranodal NK-T-Cell Biological: Alemtuzumab (Campath) Drug: EPOCH Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Trial of Alemtuzumab and Dose-Adjusted Epoch in Chemotherapy Naive Aggressive T and NK-Cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Wyndham Wilson, M.D., National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Alemtuzumab [ Time Frame: Evaluation of dose limiting toxicity was done at the end of each cycle or every 21 days. ]
    MTD was achieved by increasing doses of Alemtuzumab on three cohorts. Cohort 1 received 30mg of Alemtuzumab, cohort 2 received 60mg of Alemtuzumab, and cohort 3 received 90mg of Alemtuzumab intravenously every 3 weeks for up to 6 cycles. The MTD reflects the highest dose of Alemtuzumab in which no more than 1 of 6 participants entered at a specific dose level experienced a dose limiting toxicity (DLT).

  • Number of Participants With Adverse Events [ Time Frame: 67 months and 9 days ]
    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.


Secondary Outcome Measures:
  • Clinical Response [ Time Frame: For patients with response:Restage sites of disease every (q) 3 months for the first year, then q4 months for the second year, and then q6 months for the next 3 years, and yearly thereafter. The timing for these visits may be adjusted + 2 months. ]
    Response was measured by the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. Complete remission (CR) is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed (Cru)is as per complete remission criterion except that if a residual node is greater than 1.5cm, it must have decreased by greater than 75% in the sum of the products of the perpendicular diameters (SPD). Partial response (PR) is ≥50% decrease in the SPD of 6 largest dominant nodes or nodal masses. Progressive disease (PD) is ≥50% increase from the nadir in the SPD of any previously identified abnormal node for PRS or non-responders. Stable disease (SD) is less than a PR but not progressive disease.


Enrollment: 31
Actual Study Start Date: September 19, 2003
Estimated Study Completion Date: March 31, 2018
Primary Completion Date: June 11, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alemtuzumab Dose Escalation
Alemtuzumab (Campath) followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) every 3 weeks for up to 6 cycles. Three cohorts of 3 to 6 patients will be treated. Cohort 1 will receive 30mg of Alemtuzumab, cohort 2 will receive 60mg of Alemtuzumab, and cohort 3 will receive 90mg of Alemtuzumab. If 1 of 3 participants entered at a given dose level experiences dose limiting toxicity (DLT), up to 3 additional participants will be entered at that dose level. If 2 of 6 participants experience DLT at a particular dose level, the maximum tolerated dose (MTD) has been exceeded. The preceding dose level will be the MTD, provided 6 participants have been entered at this level and no more than 1 has experienced DLT.
Biological: Alemtuzumab (Campath)
Alemtuzumab (Campath) followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) every 3 weeks for up to 6 cycles.
Other Name: Campath
Drug: EPOCH
Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) + Alemtuzumab (Campath) every 3 weeks for up to 6 cycles.
Other Name: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin

Detailed Description:

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkins lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkins lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objective:

Determine the toxicity and maximum tolerated dose (MTD) of Alemtuzumab and EPOCH chemotherapy in untreated cluster of differentiation 52 (CD52)-expressing T and natural killer (NK) lymphoid malignancies

Eligibility:

  • CD52-expressing lymphoid malignancy.
  • Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.
  • Age greater than or equal to 17 years.
  • Adequate organ function, unless impairment due to respective organ involvement by tumor.
  • No active symptomatic ischemic heart disease, myocardial infarction or congestive heart. failure within the past year.
  • Human immunodeficiency virus (HIV) negative.
  • Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in a preliminary fashion the antitumor activity of the combination with Dose-Adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH).

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each. Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed by dose-adjusted EPOCH chemotherapy days 1-5.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   17 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • ELIGIBILITY CRITERIA:

Cluster of differentiation 52 (CD52)-expressing lymphoid malignancy, confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, National Cancer Institute (NCI). Patients with T & natural killer (NK) cell malignancy without accessible tissue for flow cytometry analysis may be treated on this study.

Patients with chemotherapy naive aggressive T & NK lymphomas, including but not limited to peripheral T cell lymphoma (not otherwise specified (nos)), gamma-delta hepatosplenic T cell lymphoma, subcutaneous panniculitis-like T cell, NK-T cell lymphoma confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Laboratory tests: Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min; bilirubin less than 2.0 mg/dl unless due to Gilbert's, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times upper limit of normal (ULN) (AST and ALT is less than or equal to 6 times ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) and; absolute neutrophil count (ANC) is greater than or equal to 1000/mm(3), platelet greater than or equal to 75,000/mm(3); unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year.

Human immunodeficiency virus (HIV) negative, because of the unknown effects of combined therapy with chemotherapy and an immunosuppressive agent on HIV progression.

Signed informed consent.

Willing to use contraception.

Not pregnant or nursing, because of the unknown effects of Alemtuzumab on the developing fetus and infant.

No serious underlying medical condition or infection that would contraindicate treatment. Patients with central nervous system (CNS) involvement are eligible for treatment on this study.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00069238


Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: Wyndham Wilson, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00069238     History of Changes
Obsolete Identifiers: NCT00072254
Other Study ID Numbers: 030304
03-C-0304
First Submitted: September 17, 2003
First Posted: September 18, 2003
Results First Submitted: October 7, 2015
Results First Posted: January 21, 2016
Last Update Posted: October 18, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wyndham Wilson, M.D., National Institutes of Health Clinical Center (CC):
Lymphoma
T-Cell Lymphoma
NK -Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Liposomal doxorubicin
Etoposide phosphate
Alemtuzumab
Doxorubicin
Prednisone
Etoposide
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors