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| ID | Type | Description | Link |
|---|---|---|---|
| UCL-BRD/05/170 | |||
| EU-20785 | |||
| EUDRACT-2006-000365-11 | |||
| CTA 21786/0201/001-0001 | |||
| CRUK-UCL-BRD/05/170-CHOP-CAMPA | |||
| UCL-CHOP-CAMPATH |
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RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from growing. Giving alemtuzumab together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of alemtuzumab when given together with combination chemotherapy and to see how well it works in treating patients with stage I , stage II , stage III, or stage IV peripheral T-cell lymphoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, dose escalation of alemtuzumab study.
Patients receive CHOP chemotherapy comprising cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients also receive alemtuzumab subcutaneously (SC) 1-3 times a week for up to 6 doses per course. Treatment repeats every 3 weeks for up to 8 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline, periodically during study treatment, and after completion of study therapy for pharmacokinetics and other correlative studies to monitor cellular immunity. Blood samples are examined by polymerase chain reaction to detect cytomegalovirus antigen and to monitor Epstein-Barr virus copy number. Samples are also analyzed by flow cytometry to quantify circulating B- and T-cells, NK-cells, monocytes, and dendritic-cells.
After completion of study therapy, patients are followed every 3 months for the first year, every 6 months for the second year, and then yearly thereafter.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alemtuzumab | Biological | |||
| cyclophosphamide | Drug | |||
| doxorubicin hydrochloride | Drug | |||
| prednisolone | Drug | |||
| vincristine sulfate | Drug | |||
| polymerase chain reaction | Genetic | |||
| flow cytometry | Other | |||
| Measure | Description | Time Frame |
|---|---|---|
| Immediate toxicity (incidence of infusion-related reactions) | ||
| Hematopoietic toxicity (number of cycles of therapy associated with neutrophils < 0.5e9/L or platelets < 50e9/L) | ||
| Incidence of infection (number of days with fever ≥ 38 degrees C, days of intravenous antibiotics, number of inpatient days, number of episodes of cytomegalovirus reactivation) |
| Measure | Description | Time Frame |
|---|---|---|
| Disease response (remission rate [complete response and partial response]) | ||
| Disease outcome (time to progression and overall survival at 2 years from completion of therapy) | ||
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DISEASE CHARACTERISTICS:
Diagnosis of peripheral T-cell lymphoma (PTCL), including the following subtypes:
Bulky stage IA and stages IB-IV disease (Ann Arbor staging system)
Expression of CD52 by the tumor
Measurable or evaluable disease
No anaplastic lymphoma kinase-positive anaplastic large-cell lymphoma
No CNS involvement with non-Hodgkin lymphoma
PATIENT CHARACTERISTICS:
WHO performance status 0-2
No presence of other serious, uncontrolled medical conditions
No significant anthracycline-related cardiac impairment
LVEF ≥ 50%
Creatinine ≤ 1.5 mg/dL
Bilirubin ≤ 2 times normal value unless due to disease
Not pregnant or nursing
Fertile patients must use effective barrier contraception during and for 1 month after completion of study treatment
No previous malignancy except adequately treated nonmelanoma skin cancer or cervical intraepithelial neoplasia
No positive serology or non-consenting to test for any of the following:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Roderick Johnson, MD | Leeds General Infirmary | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Leeds General Infirmary | Recruiting | Leeds | England | LS1 3EX | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30773077 | Derived | Phillips EH, Devereux S, Radford J, Mir N, Adedayo T, Clifton-Hadley L, Johnson R. Toxicity and efficacy of alemtuzumab combined with CHOP for aggressive T-cell lymphoma: a phase 1 dose-escalation trial. Leuk Lymphoma. 2019 Sep;60(9):2291-2294. doi: 10.1080/10428194.2019.1576870. Epub 2019 Feb 18. No abstract available. |
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| laboratory biomarker analysis |
| Other |
| pharmacological study | Other |
| Immune reconstitution (time to recover peripheral blood CD4 count to 0.2 e9/L) |
| Relative dose intensity |
| Pharmacokinetics assessment of alemtuzumab trough levels before each cycle of treatment |
| Epstein-Barr virus copy number (measured retrospectively) |
| King's College Hospital | Recruiting | London | England | SE5 9RS | United Kingdom |
|
| Royal Marsden - London | Recruiting | London | England | SW3 6JJ | United Kingdom |
|
| Christie Hospital | Recruiting | Manchester | England | M20 4BX | United Kingdom |
|
| Torbay Hospital | Recruiting | Torbay Devon | England | TQ2 7AA | United Kingdom |
|
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D054218 | Precursor T-Cell Lymphoblastic Leukemia-Lymphoma |
| D017728 | Lymphoma, Large-Cell, Anaplastic |
| D007119 | Immunoblastic Lymphadenopathy |
| D016411 | Lymphoma, T-Cell, Peripheral |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D006402 | Hematologic Diseases |
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D000072281 | Lymphadenopathy |
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| ID | Term |
|---|---|
| D000074323 | Alemtuzumab |
| D003520 | Cyclophosphamide |
| D004317 | Doxorubicin |
| D011239 | Prednisolone |
| D014750 | Vincristine |
| D016133 | Polymerase Chain Reaction |
| D005434 | Flow Cytometry |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D003630 | Daunorubicin |
| D018943 | Anthracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D011083 | Polycyclic Compounds |
| D000617 | Aminoglycosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D014748 | Vinca Alkaloids |
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D021141 | Nucleic Acid Amplification Techniques |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
| D002469 | Cell Separation |
| D003584 | Cytological Techniques |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D003592 | Cytophotometry |
| D005470 | Fluorometry |
| D008163 | Luminescent Measurements |
| D010783 | Photometry |
| D002623 | Chemistry Techniques, Analytical |
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