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

NCT00069238 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 03030403-C-0304
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell

Keywords

Lymphoma; T-Cell Lymphoma; NK -Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Alemtuzumab

  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 up to 2 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).

  up to 2 cycles of therapy, approximately 42 days

• Number of Participants With Adverse Events

  Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

  67 months and 9 days

Secondary Outcomes (1)

• Clinical Response

  From date of onstudy until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 67 months and 9 days.

Study Arms (1)

Alemtuzumab Dose Escalation

EXPERIMENTAL

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); Drug: EPOCH

Interventions

Alemtuzumab (Campath) BIOLOGICAL

Alemtuzumab (Campath) followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) every 3 weeks for up to 6 cycles.

Also known as: Campath

Alemtuzumab Dose Escalation

EPOCH DRUG

Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) + Alemtuzumab (Campath) every 3 weeks for up to 6 cycles.

Also known as: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin

Alemtuzumab Dose Escalation

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

* 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Wing MG, Moreau T, Greenwood J, Smith RM, Hale G, Isaacs J, Waldmann H, Lachmann PJ, Compston A. Mechanism of first-dose cytokine-release syndrome by CAMPATH 1-H: involvement of CD16 (FcgammaRIII) and CD11a/CD18 (LFA-1) on NK cells. J Clin Invest. 1996 Dec 15;98(12):2819-26. doi: 10.1172/JCI119110.

  PMID: 8981930 BACKGROUND

• Harris NL, Jaffe ES, Stein H, Banks PM, Chan JK, Cleary ML, Delsol G, De Wolf-Peeters C, Falini B, Gatter KC, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361-92. No abstract available.

  PMID: 8068936 BACKGROUND

• A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood. 1997 Jun 1;89(11):3909-18.

  PMID: 9166827 BACKGROUND

• Lai C, Cole DE, Steinberg SM, Lucas N, Dombi E, Melani C, Roschewski M, Balis F, Widemann BC, Wilson WH. Doxorubicin pharmacokinetics and toxicity in patients with aggressive lymphoma and hepatic impairment. Blood Adv. 2023 Feb 28;7(4):529-532. doi: 10.1182/bloodadvances.2022007431.

  PMID: 35882475 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Lymphoma, T-Cell; Lymphoma, Extranodal NK-T-Cell; Lymphoma

Interventions

Alemtuzumab; Etoposide; Prednisone; Vincristine; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides

Results Point of Contact

• Title: Dr. Wyndham WIlson
• Organization: National Cancer Institute

wilsonw@mail.nih.gov

301-435-2415

Study Officials

• Wyndham H Wilson, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 17, 2003
• First Posted: September 18, 2003
• Study Start: September 19, 2003
• Primary Completion: June 11, 2009
• Study Completion: March 17, 2021
• Last Updated: February 24, 2022
• Results First Posted: January 21, 2016

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)