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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.

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

Alemtuzumab (Campath)

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

EPOCH

Wyndham H Wilson, M.D.

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.

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.

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

Phase 2 Trial of Alemtuzumab and Dose-Adjusted Epoch in Chemotherapy Naive Aggressive T and NK-Cell Lymphomas

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).

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

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.

National Cancer Institute (NCI)

Principal Investigator

All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles.

The adverse events are not reported per dose level because we normally look at all adverse events together irrespective of the dose level.

All Participants

All participants who received at least one dose of Alemtuzumab (Campath) 30mg, 60mg, or 90mg on day 1 of therapy followed by etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH) chemotherapy intravenously every 3 weeks for up to 6 cycles.

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Wyndham WIlson

Maximum Tolerated Dose (MTD) of Alemtuzumab

Number of Participants With Adverse Events

Clinical Response

Alemtuzumab (Campath) 30mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.

Alemtuzumab 30 mg

Alemtuzumab (Campath) 60mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.

Alemtuzumab 60 mg

Alemtuzumab (Campath) 90mg intravenous (IV) on day 1 of therapy, followed by etoposide (50mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), prednisone (60mg/m(2) day by mouth (PO) day 0-5), vincristine (0.4mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), cyclophosphamide (750mg/m(2) day intravenous day 5), doxorubicin (10mg/m(2) day continuous intravenous (CIV) day 1-4 (96 hours)), (EPOCH) days 1-5 every 3 weeks for up to 6 cycles.

Alemtuzumab 90 mg

Cohort 1 - Dose Level 1 (Weeks 1 - 18)

Cohort 2 - Dose Level 2 (Weeks 1-18)

Cohort 3 - Dose Level 3 (Weeks 1-18)

Symptoms and General Pathology

Syndrome

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Hematologic Diseases

Precancerous Conditions

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Patients received a 1-mg test dose of alemtuzumab, and the following day, alemtuzumab was administered at 10 mg/dose intravenously for 10 days

Chris Hourigan, BMBCh

This study will evaluate the safety and effectiveness of a genetically engineered antibody, alemtuzumab (Campath\[R\]) on patients with myelodysplastic syndrome. MDS is made up of malignant stem cell disorders that can mean low levels of red blood cells-that is, anemia-and low counts of white blood cells and platelets. Patients with MDS are at risk for infection, spontaneous bleeding, and possible progression to leukemia, a cancer of bone marrow. Although bone marrow can produce some blood cells, patients with MDS experience a decrease in production of blood cells. Alemtuzumab recognizes specific types of white cells called lymphocytes and destroys them. This study will examine not only the usefulness of the medication but also the side effects in patients with MDS.

Patients ages 18 to 72 who have MDS that requires transfusions and who do not have HIV or a life expectancy of less than 6 months may be eligible for this study. Screening tests include a complete physical examination and medical history. There will be a collection of about 8 tablespoons of blood for analysis of blood counts as well as liver, kidney, and thyroid function; a pregnancy test; an electrocardiogram (EKG) to measure electrical activity of the heartbeat; an echocardiogram (ECHO), which uses sound waves to evaluate heart function; wearing of a Holter monitor for 24 hours while the electrical activity of the heart is recorded; and a bone marrow biopsy. Patients should not receive any vaccines when taking alemtuzumab or for at least 12 months after the last dose. In addition, patients should not take the herbal supplements Echinacea purpurea or Usnea 2 weeks before beginning the study and during it.

For the study, all patients will receive a test dose of 1 mg of alemtuzumab infused into a vein during the course of 1 hour. If the dose is tolerated, the medication will be given at 10 mg doses into the vein for 10 days, as an infusion of 2 hours. Blood samples of 2 tablespoons will be taken daily, and vital signs will be measured daily. The ECHO and 24-hour Holter monitoring will be repeated after patients receive the last dose of the medication. Because suppression of the immune system results from a decrease in white cells that fight infections, patients will take medications to protect them against infections and to treat them if infections occur. If needed, patients will receive blood transfusions for their MDS. Side effects of alemtuzumab involve a temporarily significant lowering of the number of red blood cells, white cells, and platelets. Side effects of the infusion can be rigidity, or stiffness, and fever, as well as risks of infections resulting from the decrease of white blood cells. Blood counts and reactions to all procedures will be carefully monitored throughout the study. After patients receive the last dose of alemtuzumab, they will have follow-up by their referring doctor or at NIH. They must be able to return to NIH after 1 month, 3 months, 6 months, and annually for 5 years after the study. At follow-up visits, there will be blood tests to reevaluate blood counts and test for the presence of viruses. Blood tests will be done weekly for the first 3 months after patients have completed taking alemtuzumab, every other week until 6 months, and then annually for 5 years. There will also be a repeat ECHO at the 3-month visit, and a repeat bone marrow biopsy at the 5-month and 12-month follow-up visits, and as needed after that.

This study may or may not have a direct benefit for participants. For some, the antibody may improve blood counts and decrease the need for transfusions. Knowledge gained in the study may help people in the future.

Many bone marrow failure syndromes in humans are now recognized to result from immunological mechanisms. These diseases include aplastic anemia, pure red cell aplasia, and some types of myelodysplasia. Patients with these conditions, who may suffer variable degrees of anemia, leukopenia, and thrombocytopenia, alone or in combination, have been shown to respond to a wide variety of immunosuppressive agents, ranging from corticosteroids to cyclosporine (CsA) and horse antithymocyte globulin (h-ATG). However, non-response and relapse continues to be a problem. Why some patients do not respond initially or others respond and then relapse is unclear. Autoreactive T cells may be resistant to the effect of h-ATG/CsA (non-responders), while in others, residual autoreactive T cells expand post-treatment leading to hematopoietic stem cell destruction and recurrent pancytopenia (relapse). Therefore, novel, less toxic immunosuppressive regimens that increase response rates and hematologic recovery and decrease relapse rates are needed.

One such novel therapy, alemtuzumab (Campath\[R\]) is a humanized IgG1 monoclonal antibody directed against the CD52 protein, which is highly expressed on all lymphoid cells and monocytes. Alemtuzumab (Campath\[R\]), produces profound and persistent lymphopenia, affecting predominantly the CD4+ T cell subset. This property has made it attractive in the treatment of a wide range of diseases including rheumatoid arthritis, multiple sclerosis, ocular inflammatory disease, lymphoid malignancies, organ allograft rejection, and in conditioning regimens in stem cell transplantation to prevent graft failure and graft-versus-host disease.

We therefore propose a non-randomized, off label, pilot, Phase I/II study of alemtuzumab (Campath) in MDS patients who are likely to respond to immunosuppression.

Primary endpoints will be changes in peripheral blood counts (platelets, absolute neutrophil count, reticulocyte count, hemoglobin). Secondary endpoints (in transfusion-dependent patients) include improvement in the transfusion requirements (measured as decrease in the number of transfusion administered on as needed basis), duration of response, late effects of treatment, relapse and survival.

A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome

A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome (MDS)

Response to treatment at 3 months after the first dose of alemtuzumab. The parameters for hematologic improvement (HI) and complete response (CR) were defined according to the International Working Group (IWG) criteria. The IWG criteria for HI define specific responses of cytopenias in the 3 hematopoietic lineages: erythroid (HI-E), platelet (HI-P), and neutrophil (HI-N).7 The HIs are measured in patients with pretreatment abnormal values: hemoglobin level less than 110 g/L (11 g/dL) or RBC-transfusion dependence, platelet count less than 100 × 109/L or platelet-transfusion dependence, absolute neutrophil count (ANC) less than 1.0 × 109/L.

The parameters for CR include less than 5% marrow blasts without evidence of dysplasia and normalization of peripheral blood counts, including a hemoglobin level of 110 g/L (11 g/dL) or more (in patients not receiving erythropoietin or transfusions), a neutrophil count of 1.5 × 109/L or more, and a platelet count of 100 × 109/L.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas	NCT00069238	Lymphoma, T-Cel... Lymphoma, Extra...	Alemtuzumab (Ca... EPOCH	17 Years -	National Institutes of Health Clinical Center (CC)
Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas	NCT00069238	Lymphoma, T-Cel... Lymphoma, Extra...	Alemtuzumab (Ca... EPOCH	17 Years -	National Institutes of Health Clinical Center (CC)
A Pilot Study of Alemtuzumab (Campath[R]) in Patients With Myelodysplastic Syndrome	NCT00217594	Myelodysplastic...	Alemtuzumab (Ca...	18 Years - 72 Years	National Institutes of Health Clinical Center (CC)
Campath-1H and EPOCH to Treat Non-Hodgkin's T- and NK-Cell Lymphomas	NCT00069238	Lymphoma, T-Cel... Lymphoma, Extra...	Alemtuzumab (Ca... EPOCH	17 Years -	National Institutes of Health Clinical Center (CC)

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