phase i study of kw-0761 in relapsed patients with ccr4-positive atl and ptcl

Conditions: Adult T-Cell Leukemia and Lymphoma (ATL); Adult Peripheral T-Cell Lymphoma (PTCL)

Summary: this is a phase i label dose escalation study of kw-0761 in relapsed patients with ccr4 positive adult t-cell leukemia-lymphoma (atl) and peripheral t-cell lymphoma (ptcl).

this is a phase i open-label dose escalation study of kw-0761 in relapsed patients with ccr4 positive adult t-cell leukemia-lymphoma (atl) and peripheral t-cell lymphoma (ptcl). this study is designed to evaluate safety, pharmacokinetics, immunogenicity and preliminary efficacy. enrollment will proceed until a maximum tolerated dose (mtd) and a recommended phase ii dose (rpiid) have been established.

Eligibility criteria:
inclusion criteria: 1. histologically confirmed diagnosis of a ccr4-positive atl and ptcl that is any of the following: a. atl (adult t-cell leukemia-lymphoma) * seropositive for anti-human t-lymphotrophic virus type-i (htlv-i) antibody; * acute, lymphoma, or chronic phase with high-risk factors (within 14 days before the study entry); b. ptcl (peripheral t-cell lymphoma) * includes mycosis fungoides and sezary syndrome; 2: relapsed to the latest standard chemotherapy; 3: received at least one prior chemotherapy; 4: after 4 weeks from a prior therapy; 5: have measurable disease; 6:eastern cooperative oncology group (ecog) performance status score of 0 or 1; 7: male or female, at least 20 years and not older than 70 years of age; 8: signed written informed consent; 9: stay in hospital for 4 weeks; 10: hbs antigen: negative, hbv-dna: below the limit of quantification (within 14 days before the study entry); 11: adequate bone marrow, hepatic and cardiac function including the followings: * neutrophil count ≥ 1,500 /mm3, * platelets ≥ 75,000 /mm3, * hemoglobin ≥ 8.0 g/dl * serum creatinine ≤ 1.5 x uln; * serum sgot (ast) and sgpt (alt) ≤ 2.5 x uln (≤ 5.0 x uln if considered due to disease involvement in liver); * serum bilirubin ≤ 1.5 x uln (≤ 3.0 x uln if considered due to disease involvement in liver) * serum calcium ≤ 11.0 mg/dl * pao2 ≥ 65 mmhg or sao2 ≥ 90% * no clinically significant electrocardiogram abnormality * left ventricular ejection fraction ≥ 50% \[by echo or muga\] exclusion criteria: 1. co-existing active infection or any co-existing medical condition that may compromise the safety of patients during the study, affect the patient's ability to complete the study, or interfere with interpretation of study results; 2. active tuberculosis; 3. prior stem cell transplantation; 4. myocardial infarction (within 12 months prior to the study entry); 5. concurrent acute or chronic hepatitis, or cirrhosis; 6. anti-hcv: positive, anti-hiv: positive 7. concurrent active malignant disease; 8. known allergic reaction to antibody therapy; 9. concomitant treatment with systemic steroids; 10. prior and concurrent psychiatric disorder including dementia, epilepsy or any other cns diseases; 11. evidence of cns metastasis at baseline; 12. prior and concurrent spinal cord disease; 13. radiation therapy for bulky mass disease at the time of study entry or considered to require radiation therapy during the study; 14. female patients who are pregnant or breast feeding; 15. female patients of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards; 16. treatment with any other investigational agent within the 4 months prior to study entry; 17. for any reason is judged by the investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the investigator.

Keywords: adult t-cell leukemia atl adult peripheral t-cell lymphoma ptcl