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| ID | Type | Description | Link |
|---|---|---|---|
| P50CA097274 | U.S. NIH Grant/Contract | View source | |
| P30CA015083 | U.S. NIH Grant/Contract | View source | |
| LS058C | Other Identifier | Mayo Clinic Cancer Center | |
| 06-002246 | Other Identifier | Mayo Clinic IRB |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
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RATIONALE: Combinations of biological substances in alefacept may be able to carry cancer-killing substances directly to cancer cells.
PURPOSE: This phase I trial is studying the side effects and best dose of alefacept in treating patients with relapsed or refractory cutaneous T-cell lymphoma or peripheral T-cell non-Hodgkin's lymphoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, dose-escalation study.
Cohorts of 6 patients receive escalating doses of alefacept until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. The optimal immunologic dose is defined as the dose that does not exceed the MTD, has the highest alefacept level, and achieves saturation of CD2 receptors.
Patients who experience disease progression during maintenance therapy may receive reinduction therapy* comprising 4 weekly doses of alefacept. The patient then proceeds to a second maintenance phase in the absence of disease progression.
NOTE: *Only 1 reinduction allowed.
Patients undergo blood and tissue collection periodically for pharmacological studies. Blood serum is analyzed for alefacept concentration, cytokine concentration, CD16 polymorphisms, and CD2 saturation via flow cytometry.
After completion of study treatment, patients are followed every 3 months for up to 3 years and then periodically thereafter.
PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| alefacept | Experimental | Determine both the maximum tolerated dose level as well as the optimal immunologic dose and toxicity. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Alefacept | Drug | Dose escalation theme. 0.075mg/kg by IV Weekly x 8 to 0.30mg/kg IV Weekly x 8 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Limiting Toxicity (DLT) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on toxicities encountered during the first 8 weeks of treatment.> > For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria:>
The number of patients who reported a dose limiting toxicity is reported here. | 8 weeks from registration |
| Maximum Tolerated Dose (MTD) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on DLT toxicities encountered during the first 8 weeks of treatment reported in Primary Outcome Measure #1. | 8 weeks from registration |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Response | Treatment response and evaluation will be performed using standardized lymphoma International Working Group recommendations.> > A Complete Response (CR) requires:>
Partial Response (PR):>
|
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DISEASE CHARACTERISTICS:
Histologically confirmed cutaneous T-cell lymphoma (CTCL) or peripheral T-cell non-Hodgkin's lymphoma
Relapsed or refractory disease
Patients with CTCL must have failed ≥ 2 skin-directed therapies
Measurable disease, defined as at least 1 bidimensionally measurable lesion > 2 cm by CT scan, MRI, physical exam, or photograph with appended ruler
No CNS lymphoma
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas E. Witzig, MD | Mayo Clinic | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| City of Hope Comprehensive Cancer Center | Duarte | California | 91010-3000 | United States | ||
| Holden Comprehensive Cancer Center at University of Iowa |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dose Level 1 | Starting Dose Level 1= 0.15 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| FG001 | Dose Level 2 | Starting Dose Level 1= 0.20 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| FG002 | Dose Level 3 | Starting Dose Level 1= 0.30 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dose Level 1 | Starting Dose Level 1= 0.15 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| BG001 | Dose Level 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose Limiting Toxicity (DLT) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on toxicities encountered during the first 8 weeks of treatment.> > For this protocol, dose-limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria:>
The number of patients who reported a dose limiting toxicity is reported here. | Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity. | Posted | Count of Participants | Participants | 8 weeks from registration |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Level 1 | Alefacept by IV 1 x every 4 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin decreased | Blood and lymphatic system disorders | MedDRA 6 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin decreased | Blood and lymphatic system disorders | MedDRA 6 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas E. Witzig, M.D. | Mayo Clinic | witzig.thomas@mayo.edu |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D016410 | Lymphoma, T-Cell, Cutaneous |
| D007119 | Immunoblastic Lymphadenopathy |
| D017728 | Lymphoma, Large-Cell, Anaplastic |
| D054391 | Lymphoma, Extranodal NK-T-Cell |
| D009182 | Mycosis Fungoides |
| D012751 | Sezary Syndrome |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| ID | Term |
|---|---|
| D000077944 | Alefacept |
| ID | Term |
|---|---|
| D018968 | CD58 Antigens |
| D008562 | Membrane Glycoproteins |
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
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| up to 12 cycles (28 days per cycle) of treatment. |
| Iowa City |
| Iowa |
| 52242-1002 |
| United States |
| Mayo Clinic Cancer Center | Rochester | Minnesota | 55905 | United States |
Dose Level 2= 0.20 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly>
> Cycles 3-12:> Alefacept by IV 1 x every 4 weeks
| BG002 | Dose Level 3 | Dose Level 3= 0.30 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | Dose Level 1 | Dose Level 1= 0.15 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| OG001 | Dose Level 2 | Dose Level 2= 0.20 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
| OG002 | Dose Level 3 | Dose Level 3= 0.30 mg/kg> Each cycle is 4 weeks.> > Cycle 1 and 2:> Alefacept by IV Weekly> > Cycles 3-12:> Alefacept by IV 1 x every 4 weeks |
|
|
| Secondary | Clinical Response | Treatment response and evaluation will be performed using standardized lymphoma International Working Group recommendations.> > A Complete Response (CR) requires:>
Partial Response (PR):>
| Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity. | Posted | Number | participants | up to 12 cycles (28 days per cycle) of treatment. |
|
|
|
| Primary | Maximum Tolerated Dose (MTD) | The Maximum Tolerated Dose (MTD) will be defined as the highest safely-tolerated dose where at most one out of six patients experiences a Dose Limiting Toxicity (DLT) with the next higher dose level having at least 2 patients who have experienced DLT. The MTD determination will be based on DLT toxicities encountered during the first 8 weeks of treatment reported in Primary Outcome Measure #1. | Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity. | Posted | Number | mg/kg Alefacept | 8 weeks from registration |
|
|
|
| 3 |
| 6 |
| 5 |
| 6 |
| EG001 | Dose Level 2 | Alefacept by IV 1 x every 4 weeks | 2 | 8 | 7 | 8 |
| EG002 | Dose Level 3 | Alefacept by IV 1 x every 4 weeks | 2 | 9 | 8 | 9 |
| Atrial fibrillation | Cardiac disorders | MedDRA 6 | Systematic Assessment |
|
| Death NOS | General disorders | MedDRA 6 | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA 6 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| CD4 lymphocytes decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Leukocyte count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 6 | Systematic Assessment |
|
| Rash desquamating | Skin and subcutaneous tissue disorders | MedDRA 6 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 6 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 6 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 6 | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | MedDRA 6 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 6 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Skin infection | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Upper respiratory infection | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 6 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Leukocyte count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Serum cholesterol increased | Investigations | MedDRA 6 | Systematic Assessment |
|
| Serum sodium decreased | Metabolism and nutrition disorders | MedDRA 6 | Systematic Assessment |
|
| Serum triglycerides increased | Metabolism and nutrition disorders | MedDRA 6 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 6 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA 6 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 6 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 6 | Systematic Assessment |
|
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| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D016399 | Lymphoma, T-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D000072281 | Lymphadenopathy |
| D002241 |
| Carbohydrates |
| D007074 | Immunoglobulin G |
| D007132 | Immunoglobulin Isotypes |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D008565 | Membrane Proteins |
| D011993 | Recombinant Fusion Proteins |
| D011994 | Recombinant Proteins |
|