Study of KW-0761 (Mogamulizumab) in Subjects With Previously Treated Peripheral T-cell Lymphoma (PTCL)

Peripheral T-Cell Lymphoma Clinical Trial

Official title:

Open-Label, Multi-Center, Phase 2 Study of Anti-CCR4 Monoclonal Antibody KW-0761 (Mogamulizumab) in Subjects With Previously Treated Peripheral T-cell Lymphoma (PTCL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01611142
• Other study ID #: PROTOCOL 0761-007
• Status: Completed
• Phase: Phase 2
• Start date: April 2012
• Est. completion date: May 2015

Study information

• Verified date: June 2024
• Source: Kyowa Kirin Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to determine the overall response rate of KW-0761 for the treatment of patients with relapsed or refractory PTCL. KW-0761 targets CCR4. CCR4 is the receptor for macrophage derived chemokines MDC/CCL22 and TARC/CCL17. Chemokines are considered to play a role both in the recruitment of immune and inflammatory cells for anti-tumor response and in the selective homing of neoplastic B and T cells.

Description:

PTCL is a rare and heterogeneous disease that remains difficult to diagnose and treat. In the majority of PTCL subtypes, patients are of older age (>60 years) and present with advanced stage disease.With the exception of the ALCL-ALK-positive subtype that responds well to CHOP combined chemotherapy, most PTCL subtypes become refractory even to aggressive chemotherapy regimens or relapse. Overall survival of PTCL patients is poor compared with that of aggressive B-cell lymphomas.Thus, novel and effective therapies are needed.KW-0761(mogamulizumab) is a defucosylated, humanized, IgG1 mAb with enhanced antibody dependent cellular cytotoxicity (ADCC)that binds to CCR4, a molecule that is suggested to be significantly involved in patients with PTCL.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. =18 years of age at the time of enrollment;

2. Histologically confirmed diagnosis of PTCL as specified below:

• PTCL-NOS
• Angioimmunoblastic T-cell lymphoma
• Anaplastic large cell lymphoma, ALK-positive
• Anaplastic large cell lymphoma, ALK-negative
• Transformed mycosis fungoides

3. Failed or intolerant of at least one prior systemic anticancer therapy;

4. ECOG performance status score of = 2 at study entry;

5. At least one site of disease measurable in two dimensions by computed tomography (CT);

6. Subjects who are positive for CCR4 by immunohistochemistry;

7. Resolution of all clinically significant toxic effects of prior cancer therapy to grade =1 (NCI-CTCAE, v.4.0);

8. Adequate hematological hepatic and renal function.

Exclusion Criteria:

1. Subject with the following PTCL diagnoses are excluded;

• Precursor T/NK neoplasms
• Adult T-cell leukemia-lymphoma
• T-cell prolymphocytic leukemia
• T-cell large granular lymphocytic leukemia
• Aggressive NK-cell leukemia
• Systemic EBV-positive T-cell lymphoproliferative disorder of childhood
• Hydroa vacciniforme-like lymphoma
• Mycosis fungoides, other than transformed mycosis fungoides
• Sezary Syndrome
• Primary cutaneous CD30+ disorders: Anaplastic large cell lymphoma and lymphatoid papulosis
• Primary cutaneous CD8+ aggressive epidermotropic cytoxic T-cell lymphoma
• Primary cutaneous CD4+ small/medium T-cell lymphoma
• Primary cutaneous gamma-delta T-cell lymphoma
• Extranodal NK/T T-cell lymphoma-nasal type
• Enteropathy-associated T-cell lymphoma
• Hepatosplenic T-cell lymphoma
• Subcutaneous panniculitis -like T-cell lymphoma
• Chronic lymphoproliferative disorder of NK cells

2. Have had an invasive solid tumor malignancy in the past five years except non-melanoma skin cancers, melanoma in situ, cervical carcinoma in situ, ductal/lobular carcinoma in situ of the breast, or localized prostate cancer with a current PSA of = 0.1 ng/ml who is currently without evidence of disease;

3. Relapsed less than 75 days of autologous stem cell transplant;

4. History of allogeneic stem cell transplant;

5. Evidence of central nervous system (CNS) metastasis;

6. Psychiatric illness, disability or social situation that would compromise the subject's safety or ability to provide consent, or limit compliance with study requirements;

7. Subjects with a history of moderate or severe psoriasis or with psoriasis associated with systemic symptoms e.g. arthropathy), or with a 1st degree relative with history of psoriasis that required medical intervention;

8. Significant uncontrolled intercurrent illness;

9. Known or tests positive for human immunodeficiency virus (HIV), hepatitis B or hepatitis C;

10. Active herpes simplex or herpes zoster;

11. Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins;

12. Known active autoimmune disease will be excluded (For example: Grave's disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease);

13. Is pregnant (confirmed by beta human chorionic gonadotrophin [ß-HCG]) or lactating; Prohibited Therapies and/or Medications

14. Prior treatment with KW-0761;

15. Initiation of treatment with systemic steroids while on study is only permitted for acute and brief complications of underlying disease (e.g., hypercalcemia) or for treatment related side effects;

16. Initiation of treatment with topical steroids while on study is not permitted except to treat an acute rash;

17. Have had anti-neoplastic chemotherapy, radiation, immunotherapy, or investigational medications within 4 weeks of screening visit;

18. Subjects on any immunomodulatory drug.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-Cell Lymphoma

Intervention

Biological:
• KW-0761 (mogamulizumab)
1 mg/kg administered intravenously weekly x 4 then every other week until progression

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus
France	CHU Henri Mondor	Créteil Cedex
France	CHRU Lille	Lille Cedex
France	Hopital Saint-Louis	Paris
France	Centre Hospitaliser de Lyon Sud	Pierre Benite
France	Centre Henri Becquerel	Rouen
Italy	Università di Bologna	Bologna
Netherlands	Vrije Universiteit Medisch Centrum (VUMC)	Amsterdam
Netherlands	Universitair Medisch Centrum Groningen (UMCG)	Groningen
Spain	Institut Catalá D'Oncologia, Hospital Duran y Reynals	Barcelona
Spain	Hospital Univesitario 12 de Octubre	Madrid
Spain	Hospital Clínico Universitario de Salamanca	Salamanca
United Kingdom	Guy's Hospital	London
United Kingdom	Christie Hospital	Manchester
United Kingdom	Cancer Research UK Centre/Southhampton General Hospital	SouthHampton

Sponsors (2)

Lead Sponsor	Collaborator
Kyowa Kirin Co., Ltd.	Kyowa Hakko Kirin Pharma, Inc.

Countries where clinical trial is conducted

Denmark,  France,  Italy,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate		every 8 weeks