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

NCT ID: NCT01198665

Last Updated: 2015-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-07-31
• Study Completion Date: 2014-12-31

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

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

RAD001-CHOP

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

Group Type: EXPERIMENTAL

RAD001 (Everolimus)

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Cytoxan, Doxorubicin, Vincristine, prednisolone

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: collaborator

Yonsei University

OTHER

Sponsor Role: collaborator

National Cancer Center, Korea

OTHER_GOV

Sponsor Role: collaborator

Korea Cancer Center Hospital

OTHER

Sponsor Role: collaborator

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Kim, Seok Jin

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Won Seog Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

National Cancer Center

Goyang-si, Kyoungki-do, South Korea

Samsung Medical Center

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Korea Cancer Center Hospital

Seoul, , South Korea

Yonsei Medical Center, Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

2010-01-001

Identifier Type: -

Identifier Source: org_study_id