Introduction
Patients and methods
Study design
Patients
Assessments
Safety assessment
Pharmacokinetics
Statistical analysis
Results
Patients
Characteristic | Phase 1 (n = 4) | Phase 2 (n = 44) | Total (n = 48) |
---|---|---|---|
Age, years, median (range) | 72.5 (42–76) | 69.0 (32–79) | 69.5 (32–79) |
Sex, n (%) | |||
Male | 1 (25) | 30 (68) | 31 (65) |
Female | 3 (75) | 14 (32) | 17 (35) |
ECOG PS, n (%) | |||
0 | 2 (50) | 27 (61) | 29 (60) |
1 | 2 (50) | 17 (39) | 19 (40) |
Disease classification, n (%) | |||
Peripheral T cell lymphoma, NOS | 1 (25) | 21 (48) | 22 (46) |
Angioimmunoblastic T cell lymphoma | 2 (50) | 17 (39) | 19 (40) |
Anaplastic large cell lymphoma | |||
ALK-positive | 1 (25) | 0 (0) | 1 (2) |
ALK-negative | 0 (0) | 2 (5) | 2 (4) |
Extranodal T cell/NK cell lymphoma, nasal type | 0 (0) | 1 (2) | 1 (2) |
Transformed mycosis fungoides | 0 (0) | 1 (2) | 1 (2) |
Othera | 0 (0) | 2 (5) | 2 (4) |
Ann Arbor classification,bn (%) | |||
Stage I | 0 (0) | 1 (2) | 1 (2) |
Stage II | 3 (75) | 9 (20) | 12 (25) |
Stage III | 0 (0) | 20 (45) | 20 (42) |
Stage IV | 1 (25) | 13 (30) | 14 (29) |
LDH (baseline) | |||
Low/normal | 2(50.0) | 24 (55) | 26 (54) |
High | 2(50.0) | 20 (45) | 22(46) |
Prior treatment regimens | |||
Median (range) | 2 (1–9) | 2 (1–6) | 2 (1–9) |
Chemotherapy, n (%) | 4 (100) | 44 (100) | 48 (100) |
ASCT, n (%) | 0 (0) | 3 (7) | 3 (6) |
Radiation therapy, n (%) | 1 (25) | 5 (11) | 6 (13) |
Monoclonal antibody, n (%) | 1 (25) | 3 (7) | 4 (8) |
Corticosteroid, n (%) | 1 (25) | 2 (5) | 3 (6) |
Response to most recent treatment regimen, n (%) | |||
CR/CRu | 3 (75) | 20 (45) | 23 (48) |
PR | 1 (25) | 24 (55) | 25 (52) |
Safety
Adverse event | All grades, n (%) | Grade 3/4, n (%) |
---|---|---|
Hematologic toxicities | ||
Lymphopenia | 48 (100) | 46 (96) |
Leukopenia | 35 (73) | 20 (42) |
Neutropenia | 27 (56) | 17 (35) |
Thrombocytopenia | 23 (48) | 12 (25) |
Anemia | 23 (48) | 11 (23) |
Febrile neutropenia | 6 (13) | 6 (13) |
Non-hematologic toxicities | ||
Constipation | 13 (27) | 1 (2) |
Nasopharyngitis | 13 (27) | 0 (0) |
Hypoalbuminemia | 12 (25) | 2 (4) |
Edema | 12 (25) | 0 (0) |
Pyrexia | 11 (23) | 1 (2) |
Stomatitis | 11 (23) | 1 (2) |
Headache | 11 (23) | 0 (0) |
Insomnia | 10 (21) | 0 (0) |
Alanine aminotransferase increased | 10 (21) | 1 (2) |
Nausea | 9 (19) | 1 (2) |
Decreased appetite | 9 (19) | 4 (8) |
Malaise | 8 (17) | 0 (0) |
Aspartate aminotransferase increased | 8 (17) | 0 (0) |
Rash | 8 (17) | 0 (0) |
Abnormal hepatic function | 7 (15) | 3 (6) |
Herpes zoster | 7 (15) | 1 (2) |
Pruritus | 7 (15) | 0 (0) |
Protein in urine | 7 (15) | 0 (0) |
Vomiting | 6 (13) | 0 (0) |
Cytomegalovirus infection | 5 (10) | 0 (0) |
Pneumonia | 5 (10) | 4 (8) |
Hyponatremia | 5 (10) | 4 (8) |
Decreased weight | 5 (10) | 1 (2) |
Disease classification | Sex | Agea | Duration of forodesine administration (days) | Duration to development of sBCLb (days) | Treatments for sBCL/response | Outcome |
---|---|---|---|---|---|---|
AITL | F | 71 | 447 | 450 | R-DeVIC/CR | Alive with AITL |
AITL | F | 70 | 171 | 203 | R-CHOP/PD | Died from lymphoma (AITL, sBCL) |
AITL | F | 76 | 67 | 436 | PSL/unknown | Died from lymphoma (AITL, sBCL) |
PTCL, NOS | F | 72 | 353 | 281 | PSL/unknown | unknown |
PTCL, NOS | F | 65 | 505 | 506 | R-COP/PD R-CHOP/PD DEX/PD | Died from lymphoma (PTCL, NOS, sBCL) |
Efficacy
Response, n (%) | Phase 2 (n = 41) | Phase 1 + 2 (n = 45) |
---|---|---|
Primary analysis | ||
DCR (CR + PR+ SD) | 16 (39) | 17 (38) |
ORR (CR + PR) 90% CI | 9 (22)a 12–35 | 10 (22) 13–35 |
CR | 4 (10) | 4 (9) |
PR | 5 (12) | 6 (13) |
SD | 7 (17) | 7 (16) |
PD/RD | 24 (59) | 26 (58) |
Not evaluable | 1 (2) | 2 (4) |
Final analysis | ||
DCR (CR + PR+ SD) | 16 (39) | 17 (38) |
ORR (CR + PR) 90% CI | 10 (25)a 14–38 | 11 (24) 14–37 |
CR | 4 (10) | 4 (9) |
PR | 6 (15) | 7 (16) |
SD | 6 (15) | 6 (13) |
PD/RD | 24 (59) | 26 (58) |
Not evaluable | 1 (2) | 2 (4) |
Subgroup | n/Na | ORR (95% CI), % |
---|---|---|
All evaluable patients in phases 1 + 2 | 11/45 | 24 (13–40) |
Sex | ||
Men | 8/30 | 27 (12–46) |
Women | 3/15 | 20 (4–48) |
Age group | ||
< 65 years | 6/16 | 38 (15–65) |
≥ 65 years | 5/29 | 17 (6–36) |
No. of previous anti-tumor regimens | ||
1 | 5/19 | 26 (9–51) |
2 | 3/9 | 33 (8–70) |
3 | 3/10 | 30 (7–65) |
≥ 4 | 0/7 | 0 (0–41) |
Histological classification | ||
Peripheral T cell lymphoma, NOS | 5/22 | 23 (8–45) |
Angioimmunoblastic T cell lymphoma | 6/18 | 33 (13–59) |
Ann Arbor stageb | ||
Stage I | 0/1 | 0 (0–98) |
Stage II | 2/11 | 18 (2–52) |
Stage III | 7/19 | 37 (16–62) |
Stage IV | 2/13 | 15 (2–45) |
ECOG performance status | ||
0 | 7/27 | 26 (11–46) |
1 | 4/18 | 22 (6–48) |
Target lesion SPD | ||
< 14 cm2 | 8/26 | 31 (14–52) |
≥ 14 cm2 | 3/19 | 16 (3–40) |
LDH | ||
Low/normal | 9/25 | 36 (18–58) |
High | 2/20 | 10 (1–32) |