RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas

Cutaneous T Cell Lymphoma Clinical Trial

— RADCHOP  

Official title:

A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01198665
• Other study ID #: 2010-01-001
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 8, 2010
• Last updated: March 1, 2015
• Start date: July 2010
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial Summary

The urgent need for new effective therapy for T-cell lymphoma patients and promising results observed so far in trials with RAD001(everolimus, mTOR inhibitor) strongly warrants the investigation of RAD001 combined with CHOP as a first-line treatment in peripheral T-cell lymphoma patients.

Thus, we designed a phase I/II study with the combination of RAD001 with CHOP chemotherapy for newly diagnosed peripheral T-cell lymphoma patients.

Phase I

1. Primary objective

: To define the maximum tolerable dose

2. Secondary objective

• To evaluate the dose-limiting toxicity

• To evaluate the pharmacokinetics of RAD001

• Pharmacogenomic profiling

Phase II

1. Primary objective

: To evaluate the overall response rate

2. Secondary objective

• To estimate the time to progression

• To estimate overall survival

• Pharmacogenomic profiling

Description:

Phase I Level 1: RAD001 2.5 mg PO daily D1-14 + CHOP Level 2: RAD001 5 mg PO daily D1-14 + CHOP Level 3: RAD001 7.5 mg PO daily D1-14 + CHOP Level 4: RAD001 10 mg PO daily D1-14 + CHOP CHOP every 3 weeks D1 Cytoxan 750mg/m2 + D5W 100ml MIV over 1hr D1 Doxorubicin 50mg/m2 + D5W 100ml MIV over 30mins D1 Vincristine 1.4mg/m2 (max.2mg) IV push D1-D5 Prednisolone 100mg/d PO (40-30-30) Phase II Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Histologically proven peripheral T-cell lymphoma, unspecified, (PTCL), ALK-negative anaplastic large cell T-cell lymphoma (ALCL), Angioimmunoblastic T cell lymphoma (AITL), Cutaneous T-cell lymphoma

2. Adequate organ function as defined by the following criteria:

A.Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase (SGOT)) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase (SGPT)) =2.5 x local laboratory upper limit of normal (ULN), or AST and ALT less than or equal to 5 x ULN if liver function abnormalities are due to underlying malignancy B.Total serum bilirubin =1.5 x ULN C.Absolute neutrophil count (ANC) =1500/µL D.Platelets =100,000/µL E.Hemoglobin =9.0 g/dL (may be transfused or erythropoietin treated) F.Serum calcium =12.0 mg/dL G.Serum creatinine =1.5 x ULN

3. At least one measurable lesion

4. ECOG PS 0-2

5. Informed consent

6. Age 20 to 70 years old

Exclusion Criteria:

1. Prior radiation therapy or surgery within 4 weeks prior to study entry

2. History of central nervous system (CNS) metastases

3. Ongoing cardiac dysrhythmias of NCI CTCAE grade =2.

4. Pregnancy or breastfeeding.

5. Hepatitis B virus surface antigen positive

6. Extranodal NK/T cell lymphoma

7. Mycosis fungoides

8. ALK-positive Anaplastic large cell lymphoma

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anaplastic Large Cell Lymphoma, ALK-negative
• Angioimmunoblastic T Cell Lymphoma
• Cutaneous T Cell Lymphoma
• Lymphoma
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Peripheral T Cell Lymphoma Unspecified

Intervention

Drug:
• RAD001 (Everolimus)
Phase I Level 1: RAD001 2.5 mg PO daily D1-14 + CHOP Level 2: RAD001 5 mg PO daily D1-14 + CHOP Level 3: RAD001 7.5 mg PO daily D1-14 + CHOP Level 4: RAD001 10 mg PO daily D1-14 + CHOP CHOP every 3 weeks D1 Cytoxan 750mg/m2 + D5W 100ml MIV over 1hr D1 Doxorubicin 50mg/m2 + D5W 100ml MIV over 30mins D1 Vincristine 1.4mg/m2 (max.2mg) IV push D1-D5 Prednisolone 100mg/d PO (40-30-30) Phase II Determined dosage of RAD001 + CHOP every 3 weeks

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si	Kyoungki-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea Cancer Center Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Yonsei Medical Center, Severance Hospital	Seoul

Sponsors (5)

Lead Sponsor	Collaborator
Samsung Medical Center	Asan Medical Center, Korea Cancer Center Hospital, National Cancer Center, Korea, Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	determination of the maximum tolerable dose and evaluation of response rate		Phase I for maximal tolerable dose and phase II for efficacy	Yes
Secondary	doe-limiting toxicity and pharmacogenomics	Phase I; To evaluate the dose-limiting toxicity; To evaluate the pharmacokinetics of RAD001; Pharmacogenomic profiling Phase II; To estimate the time to progression; To estimate overall survival; Pharmacogenomic profiling	Phase I/II	Yes