A Phase 2 interventional study of Alemtuzumab in Acute T-Cell Leukemia-Lymphoma, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2012-10-31.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
This study will examine the safety and effectiveness of Alemtuzumab (Campath-1H) for treating patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called human T-cell lymphotrophic virus type-1 (HTLV-1) that infects lymphocytes (white blood cells) called T-cells. Cancerous cells can be found not only in the blood, but also in the skin, lungs, lymph nodes, liver, bone, bone marrow, spleen, and meninges (tissues covering the brain). There are four categories of ATL, based on the aggressiveness of disease-smoldering, chronic, lymphoma, and acute. Campath-1H is a monoclonal antibody that attaches to and kills normal and cancerous lymphocytes, including T cells. Although Campath-1H is an experimental drug for treating ATL, it is approved by the Food and Drug Administration for treating chronic lymphocytic leukemia.
Patients 18 years of age and older with any type of ATL except smoldering may be eligible for this study. Candidates are screened with a medical history and physical examination, photos of skin lesions, measurement of lesions such as lymph nodes and skin nodules, blood and urine tests, electrocardiogram (EKG), chest x-ray, computed tomography (CT) scan or ultrasound of the abdomen, skin biopsy, bone marrow aspirate and biopsy, skin test, and lumbar puncture (spinal tap). Participants undergo treatment in two phases, as follows:
In addition to treatment, patients are evaluated with the following tests and procedures:
Patients receive treatment for up to 12 weeks. Treatment may stop earlier if the patient achieves a complete response before the end of 12 weeks. Patients completing the study are followed periodically with a history and physical examination, blood and urine tests, tumor evaluation, skin biopsy and skin testing. They are seen monthly at first and then at 3-month intervals the first year; every 4 months the second year, every 6 months for the third through fifth years, and then yearly.
Background:
Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder caused by an infection with the human T-cell lymphotrophic virus type-1 (HTLV-1).
ATL is characterized by rapidly rising peripheral blood leukemia cell counts, lymphadenopathy, lytic bone lesions, hepatosplenomegaly, and skin and solid organ involvement by tumor.
Chemotherapy has shown modest activity and the treatment of ATL has remained largely undefined and the survival of ATL patients poor.
The CD52 surface glycoantigen is overexpressed on ATL cells.
Alemtuzumab (Campath-1H) is a humanized rat monoclonal antibody that binds to CD52 and is cytotoxic.
In preclinical models, Campath-1H inhibited tumor growth and improved the survival of Non-obese diabetic (NOD)/severe combined immune deficiency (SCID) mice injected with human MET-1 ATL cells.
Objectives:
To determine the efficacy of Campath-1H in the treatment of ATL.
To define the time course of Campath-1H saturation in patients with ATL.
To define the toxicity of Campath-1H in patients with ATL.
Eligibility:
Patients with HTLV-I-associated adult T-cell leukemia.
More than 10% of the malignant cells must express CD52 and CD25.
Patients must have measurable disease.
The patient must have a granulocyte count of at least 1000/mm(3) and a platelet count of greater than or equal to 50,000/mm(3).
Design:
A single institution non-randomized open-label Phase II trial.
This trial will recruit a maximum of 30 eligible patients.
Patients will receive antimicrobial and antiviral prophylaxis while on-study due to the known immunosuppressive effects of Campath-1H.
Patients will receive I.V. Campath-1H 3 mg on day 1, 10 mg on day 2, and 30 mg day 3 followed by maintenance Campath-1H 30 mg I.V. three time per week.
Patients will be evaluated for response and continuation of Campath-1H therapy after weeks 4 and 8 of maintenance treatment.
Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 29 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Infusion of Campath-1H 3 mg on day # 1, 10 mg on day #2, and 30 mg day # 3 followed by maintenance Campath-1H 30 mg intravenously three times per week.
Biological: Alemtuzumab
Infusion of Campath-1H 3 mg on day # 1, 10 mg on day #2, and 30 mg day # 3 followed by maintenance Campath-1H 30 mg intravenously three times per week. Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.
Overall Response Rate
Overall response rate is defined as the percentage of participants with response and utilizes the International Standardized workshop definition. Complete response(CR)-Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Please see the protocol Link module for the full criteria if desired.
Time frame: 60 months
Overall Survival
Time between the first day of treatment to the day of death.
Time frame: 60 months
Time to Progression
Time between the first day of treatment to the day of disease progression which is defined as a persistent (at least two determinations) doubling of the peripheral blood leukemic cell count, the development of new lesions, or Ca elevations that are uncontrolled by conventional therapeutic procedures.
Time frame: 60 months
Cell Surface Expression of CD52 on Tumor Cells
The CD52 antibody-binding capacity (ABC) value is the measurement of the mean value of the maximum capacity of each cell to bind the anti-CD52 and when determined under conditions of saturating levels of antibody measures number of mean surface CD52 antigens per cell. CD52 ABC is negative when 100% saturation by therapeutic antibody is achieved.
Time frame: 6 months
The Number of Participants With Adverse Events
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
Time frame: 18 months
Anticipate enrolling 10-12 patients per year into the Campath-1H trial. Thus, if the trial goes to completion (2nd stage)we anticipate enrolling the 29 patients in approximately 2.5 years.
| Milestone | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Started | 29 |
| Completed | 7 |
| Not completed | 22 |
| Withdrew: Adverse event | 2 |
| Withdrew: Disease progression | 20 |
Overall response rate is defined as the percentage of participants with response and utilizes the International Standardized workshop definition. Complete response(CR)-Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Please see the protocol Link module for the full criteria if desired.
| percentage of participants | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Overall Response Rate | 52 (32.5 to 70.6) |
Time between the first day of treatment to the day of death.
| months | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Overall Survival | 5.9 (4.7 to 8.7) |
Time between the first day of treatment to the day of disease progression which is defined as a persistent (at least two determinations) doubling of the peripheral blood leukemic cell count, the development of new lesions, or Ca elevations that are uncontrolled by conventional therapeutic procedures.
| months | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Time to Progression | 2.0 (1.0 to 3.9) |
The CD52 antibody-binding capacity (ABC) value is the measurement of the mean value of the maximum capacity of each cell to bind the anti-CD52 and when determined under conditions of saturating levels of antibody measures number of mean surface CD52 antigens per cell. CD52 ABC is negative when 100% saturation by therapeutic antibody is achieved.
| ABC value | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Cell Surface Expression of CD52 on Tumor Cells | 82.15 ± 13.7 |
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.
| participants | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| The Number of Participants With Adverse Events | 8 |
Collected over 5 years. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Campath-1H Treatment of Adult T-cell Leukemia (ATL) | — | 8/29 (27.6%) | 29/29 (100%) |
| Event | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| CONSTITUTIONAL SYMPTOMS:: Constitutional Symptoms-Other (death)General disorders | 2/29 |
| CARDIOVASCULAR (GENERAL):: HypotensionVascular disorders | 1/29 |
| CONSTITUTIONAL SYMPTOMS:: Fatigue (lethargy, malaise, asthenia)General disorders | 1/29 |
| CONSTITUTIONAL SYMPTOMS:: Rigors, chillsGeneral disorders | 1/29 |
| ENDOCRINE:: Endocrine-Other (Endocrine:hyperthyroidism graves disease)Endocrine disorders | 1/29 |
| GASTROINTESTINAL:: VomitingGastrointestinal disorders | 1/29 |
| INFECTION/FEBRILE NEUTROPENIA:: Infection without neutropeniaInfections and infestations | 1/29 |
| METABOLIC/LABORATORY:: HypercalcemiaMetabolism and nutrition disorders | 1/29 |
| NEUROLOGY:: Neurology-Other (Unresponsiveness)Nervous system disorders | 1/29 |
| OCULAR/VISUAL:: Vision-blurred visionEye disorders | 1/29 |
| Event | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| CONSTITUTIONAL SYMPTOMS:: Rigors, chillsGeneral disorders | 25/29 |
| CONSTITUTIONAL SYMPTOMS:: Fever (in the absence of neutropenia, where neutropenia is defined as AGC<General disorders | 22/29 |
| BLOOD/BONE MARROW:: HemoglobinInvestigations | 20/29 |
| BLOOD/BONE MARROW:: LymphopeniaInvestigations | 18/29 |
| BLOOD/BONE MARROW:: PlateletsInvestigations | 16/29 |
| BLOOD/BONE MARROW:: Leukocytes (total WBC)Investigations | 15/29 |
| HEPATIC:: HypoalbuminemiaHepatobiliary disorders | 14/29 |
| METABOLIC/LABORATORY:: HyperglycemiaInvestigations | 13/29 |
| HEPATIC:: SGOT (AST) (serum glutamic oxaloacetic transaminase)Hepatobiliary disorders | 12/29 |
| BLOOD/BONE MARROW:: Neutrophils/granulocytes (ANC/AGC)Investigations | 11/29 |
| Age, Categorical(Participants) | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 25 |
| >=65 years | 4 |
| Age Continuous(years) | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Mean | 52.54 ± 13.39 |
| Sex: Female, Male(Participants) | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| Female | 19 |
| Male | 10 |
| Region of Enrollment(participants) | Campath-1H Treatment of Adult T-cell Leukemia (ATL) |
|---|---|
| United States | 29 |
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