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

Phase 1

Completed

• Conditions: Anaplastic Large Cell Lymphoma, ALK-negative; Peripheral T Cell Lymphoma Unspecified; Angioimmunoblastic T Cell Lymphoma; Cutaneous T Cell Lymphoma
• Interventions: Drug: RAD001 (Everolimus)

• Registration Number: NCT01198665
• Lead Sponsor: Samsung Medical Center

Brief 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

Detailed 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

Study Timeline

• Study Start: 2010-07
• Study First Submitted: 2010-09-08
• Study First Submitted QC: 2010-09-08
• Study First Posted: 2010-09-10
• Primary Completion: 2014-12
• Study Completion: 2014-12
• Status Verified: 2015-03
• Last Update Submitted: 2015-03-01
• Last Update Posted: 2015-03-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAD001-CHOP	RAD001 (Everolimus)	Prospective multicenter open-label phase I/II study Phase I: RAD001 2.5 - 10 mg PO daily D1-14 + CHOP every 3 weeks Phase II: Determined dosage of RAD001 + CHOP every 3 weeks Treatment will be continued until planned 6 cycles or disease progression

Primary Outcome Measures

Name	Time	Method
determination of the maximum tolerable dose and evaluation of response rate	Phase I for maximal tolerable dose and phase II for efficacy

Secondary Outcome Measures

Name	Time	Method
doe-limiting toxicity and pharmacogenomics	Phase I/II	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

Trial Locations

Locations (5)

National Cancer Center; 🇰🇷 Goyang-si, Kyoungki-do, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Yonsei Medical Center, Severance Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea Cancer Center Hospital; 🇰🇷 Seoul, Korea, Republic of