Trial Outcomes & Findings for Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma (NCT NCT00438802)

Last Updated: 2019-08-13

Results Overview

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:\> * grade 4 toxicity for neutrophils (\<0.5 x 109/L) or platelets (\<25 x 109/L)\> * any grade 3 or higher solid organ toxicity not explainable by another obvious cause.\> * more than 10 x ULN AST toxicity for more than 14 days\> * any grade 4 infection.\> The number of patients who reported a dose limiting toxicity is reported here.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

23 participants

Primary outcome timeframe

8 weeks from registration

Results posted on

2019-08-13

Participant Flow

Participant milestones

Participant milestones
Measure	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	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	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
Overall Study STARTED	6	8	9
Overall Study COMPLETED	6	8	9
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Alefacept in Treating Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma or Peripheral T-Cell Non-Hodgkin's Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 n=6 Participants 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	Dose Level 2 n=8 Participants 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	Dose Level 3 n=9 Participants 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	Total n=23 Participants Total of all reporting groups
Age, Continuous	50.5 years n=5 Participants	69 years n=7 Participants	66 years n=5 Participants	64 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	12 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants
Region of Enrollment United States	6 participants n=5 Participants	8 participants n=7 Participants	9 participants n=5 Participants	23 participants n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks from registration

Population: Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity.

Outcome measures

Outcome measures
Measure	Dose Level 3 n=9 Participants 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	All Patients n=6 Participants Dose Level 1= 0.15 mg/kg\> Dose Level 2= 0.20 mg/kg\> 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	Dose Level 2 n=6 Participants 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
Dose Limiting Toxicity (DLT)	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 8 weeks from registration

Population: Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity.

Outcome measures

Outcome measures
Measure	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	All Patients n=21 Participants Dose Level 1= 0.15 mg/kg\> Dose Level 2= 0.20 mg/kg\> 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	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
Maximum Tolerated Dose (MTD)	—	0.30 mg/kg Alefacept	—

SECONDARY outcome

Timeframe: up to 12 cycles (28 days per cycle) of treatment.

Population: Two patients from Dose level 2 were not able to complete cycle 1 and were not evaluated for dose limiting toxicity.

Treatment response and evaluation will be performed using standardized lymphoma International Working Group recommendations.\> \> A Complete Response (CR) requires:\> * Complete disappearance of all detectable clinical and radiographic evidence of\> disease.\> * All lymph nodes and nodal masses must have regressed to normal size.\> Partial Response (PR):\> * greater than 50% decrease in Sum of Product Dimensions of the six largest dominant nodes, nodal masses, or skin lesions.\> * No increase in size of other nodes\> * no new sites of disease.

Outcome measures

Outcome measures
Measure	Dose Level 3 n=9 Participants 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	All Patients n=6 Participants Dose Level 1= 0.15 mg/kg\> Dose Level 2= 0.20 mg/kg\> 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	Dose Level 2 n=6 Participants 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
Clinical Response Partial Response (PR)	0 participants	2 participants	1 participants
Clinical Response Complete Response (CR)	0 participants	1 participants	0 participants

Adverse Events

Dose Level 1

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Dose Level 2

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Dose Level 3

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dose Level 1 n=6 participants at risk Alefacept by IV 1 x every 4 weeks	Dose Level 2 n=8 participants at risk Alefacept by IV 1 x every 4 weeks	Dose Level 3 n=9 participants at risk Alefacept by IV 1 x every 4 weeks
Blood and lymphatic system disorders Hemoglobin decreased	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Cardiac disorders Atrial fibrillation	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
General disorders Death NOS	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
General disorders Disease progression	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Infections and infestations Pneumonia	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Infections and infestations Skin infection	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Investigations CD4 lymphocytes decreased	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Investigations Leukocyte count decreased	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Investigations Neutrophil count decreased	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Nervous system disorders Peripheral motor neuropathy	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders Rash desquamating	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1

Other adverse events

Other adverse events
Measure	Dose Level 1 n=6 participants at risk Alefacept by IV 1 x every 4 weeks	Dose Level 2 n=8 participants at risk Alefacept by IV 1 x every 4 weeks	Dose Level 3 n=9 participants at risk Alefacept by IV 1 x every 4 weeks
Blood and lymphatic system disorders Hemoglobin decreased	66.7% 4/6 • Number of events 21	62.5% 5/8 • Number of events 30	55.6% 5/9 • Number of events 13
Gastrointestinal disorders Oral pain	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
General disorders Chills	16.7% 1/6 • Number of events 2	12.5% 1/8 • Number of events 1	0.00% 0/9
General disorders Fatigue	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Immune system disorders Cytokine release syndrome	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Immune system disorders Hypersensitivity	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1
Infections and infestations Pneumonia	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Infections and infestations Sinusitis	16.7% 1/6 • Number of events 4	0.00% 0/8	0.00% 0/9
Infections and infestations Skin infection	0.00% 0/6	0.00% 0/8	33.3% 3/9 • Number of events 4
Infections and infestations Upper respiratory infection	16.7% 1/6 • Number of events 2	12.5% 1/8 • Number of events 1	0.00% 0/9
Infections and infestations Urinary tract infection	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Investigations Alanine aminotransferase increased	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Investigations Alkaline phosphatase increased	33.3% 2/6 • Number of events 4	0.00% 0/8	0.00% 0/9
Investigations Aspartate aminotransferase increased	50.0% 3/6 • Number of events 10	50.0% 4/8 • Number of events 8	0.00% 0/9
Investigations Leukocyte count decreased	33.3% 2/6 • Number of events 6	12.5% 1/8 • Number of events 1	11.1% 1/9 • Number of events 2
Investigations Lymphocyte count decreased	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Investigations Neutrophil count decreased	33.3% 2/6 • Number of events 8	25.0% 2/8 • Number of events 3	11.1% 1/9 • Number of events 1
Investigations Platelet count decreased	33.3% 2/6 • Number of events 7	25.0% 2/8 • Number of events 2	33.3% 3/9 • Number of events 5
Investigations Serum cholesterol increased	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1
Metabolism and nutrition disorders Serum sodium decreased	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Metabolism and nutrition disorders Serum triglycerides increased	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1
Musculoskeletal and connective tissue disorders Myalgia	16.7% 1/6 • Number of events 1	0.00% 0/8	0.00% 0/9
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6	12.5% 1/8 • Number of events 1	0.00% 0/9
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/6	0.00% 0/8	11.1% 1/9 • Number of events 1
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/6	25.0% 2/8 • Number of events 21	11.1% 1/9 • Number of events 1

Additional Information

Thomas E. Witzig, M.D.

Mayo Clinic

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place