Phase II Trial of Alemtuzumab (Campath) and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in Relapsed or Refractory Diffuse Large B-Cell and Hodgkin Lymphomas

NCT01030900 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 10001110-C-0011
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Studies conducted at the National Cancer Institute suggest that certain chemotherapy drugs may be more effective if given by continuous infusion into the vein rather than by the standard method of rapid intravenous injection. One combination of six chemotherapy drugs, known as etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R), has had a high degree of effectiveness in people with certain kinds of cancer.
• Recent evidence also indicates that the effects of chemotherapy may be improved by combining the treatment with monoclonal antibodies, which are purified proteins that are specially made to attach to foreign substances such as cancer cells. A monoclonal antibody called campath (alemtuzumab) has been manufactured to attach to a protein called Campath-1 antigen (CD52) that may target tumor cells or the surrounding inflammatory cells.
• Researchers are interested in developing new treatments for large B-cell lymphoma or Hodgkin lymphoma that can best be treated with chemotherapy. This protocol is specifically for people with diffuse large B-cell or Hodgkin lymphomas that have not responded to standard treatments. Objectives: \- To test whether giving campath (alemtuzumab) in combination with continuous infusion EPOCH-R chemotherapy will improve the outcome of lymphoma treatment. Eligibility: \- Individuals 18 years of age and older who have large B-cell lymphoma or Hodgkin lymphoma that has not responded well to standard treatments. Design:
• During the study, patients will receive standard EPOCH-R chemotherapy, which includes the following drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. The additional drug, campath, will be given by intravenous (IV) infusion on the first day of treatment over several hours.
• When the campath IV infusion and rituximab IV infusion are complete, the drugs doxorubicin, etoposide, and vincristine will each be given by continuous IV infusion over the next 4 days (that is, continuously for a total of 96 hours). Cyclophosphamide will be given by IV infusion over several hours on Day 5. Prednisone will be given by mouth twice each day for 5 days.
• Patients may be given other drugs to treat the side effects of chemotherapy, to prevent possible infections, and to improve white blood cell counts.
• The campath-EPOCH-R therapy will be repeated every 21 days, as a cycle of therapy, for a total of 6 cycles. Following the fourth and sixth treatment cycles (approximately weeks 12 and 18) of campath-EPOCH-R treatment, study researchers will perform blood tests and computed tomography (CT)/magnetic resonance imaging (MRI) scans on all patients to assess their response to the treatment.

Conditions

Hodgkin Lymphoma; Diffuse Large B-Cell Lymphoma

Keywords

Immunosuppression; Microenvironment; Hodgkin Lymphoma; Microarray; B-Cell Lymphoma; Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  PFS is the time interval from start of treatment to documented evidence of disease progression estimated using a Kaplan Meier curve. Progression was assessed by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas and is defined as ≥50% increase from nadir in the sum of the products of diameters of any previously identified abnormal node for partial response or non-responders. And an appearance of any new lesion during or at the end of therapy.

  Time of progression or death, approximately 10 months

• Overall Survival (OS)

  OS is from enrollment to the day of death estimated using the Kaplan-Meier curve.

  Median overall survival from enrollment to the day of death, approximately 17.9 months

Secondary Outcomes (1)

• Clinical Response on Study and at Relapse After Dose Adjusted - Etoposide + Prednisone + Vincristine + Cyclophosphamide + Doxorubicin + Rituximab (DA-EPOCH-RC)

  On study and at relapse after study treatment, approximately 10 months

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 58 months and 18 days.

Study Arms (1)

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath

EXPERIMENTAL

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin (EPOCH) + Rituximab + campath every 3 weeks for six cycles

Biological: Campath; Biological: Rituximab; Drug: EPOCH

Interventions

Campath BIOLOGICAL

campath plus etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and rituximab every 3 weeks for up to 6 cycles

Also known as: Alemtuzumab

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath

Rituximab BIOLOGICAL

rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) and campath every 3 weeks for up to 6 cycles

Also known as: Rituxan

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath

EPOCH DRUG

Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) plus rituximab and campath every 3 weeks for up to 6 cycles

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

Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath

Eligibility Criteria

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

You may qualify if:

• Previously treated or refractory classical large B-cell lymphomas, Grey-zone lymphoma and Hodgkin lymphoma, including Lymphocyte predominant Hodgkin Lymphoma (LPHL).
• Confirmed pathological diagnosis by the Laboratory of Pathology, National Cancer Institute (NCI).
• Age greater than or equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance 0-2
• Laboratory tests: absolute neutrophil count (ANC) greater than or equal to 1000/mm(3), platelet greater than or equal to 75,000/mm(3). Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 5 times the upper limit of normal (ULN). Total bilirubin \< 2.0 mg/dl except \< 5mg/dL in patients with Gilbert's (as defined as \> 80% unconjugated hyperbilirubinemia without other known cause); unless impairment due to organ involvement by lymphoma.

You may not qualify if:

• Active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year. If echocardiogram (ECHO) is obtained, the left ventricular ejection fraction (LVEF) should exceed 40%.
• Human immunodeficiency virus (HIV) positive, because of the unknown effects of combined therapy with chemotherapy and an immunosuppressive agent on HIV progression.
• Female subject of child-bearing potential not willing to use an acceptable method of birth control (i.e. a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and two years beyond treatment completion.
• Female subject pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotrophin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for women without childbearing potential.
• Male subject unwilling to use an acceptable method for contraception for the duration of the study and one year beyond treatment completion.
• Invasive or active malignancy in past 2 years.
• Serious concomitant medical illnesses that would jeopardize the patient s ability to receive the regimen with reasonable safety.
• Active central nervous system (CNS) lymphoma. These patients have a poor prognosis and because they frequently develop progressive neurological dysfunction that would confound the evaluation of neurological and other adverse events.
• Systemic cytotoxic therapy within 3 weeks of treatment.

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 Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell

Interventions

Alemtuzumab; Rituximab; Etoposide; Prednisone; Vincristine; Cyclophosphamide; Doxorubicin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; 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

(240) 760-6092

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: December 11, 2009
• First Posted: December 14, 2009
• Study Start: October 22, 2009
• Primary Completion: August 6, 2021
• Study Completion: August 6, 2021
• Last Updated: October 6, 2022
• Results First Posted: October 6, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)