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

Samsung Medical Center

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: RAD001 (Everolimus)

Study type: Interventional

Funder types: Other

Identifiers

NCT01198665

2010-01-001

Details and patient eligibility

About

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

Full 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

Enrollment: 46 patients

Sex: All

Ages: 20 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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46 participants in 1 patient group

RAD001-CHOP

Experimental group

Description:

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

Treatment:

Drug: RAD001 (Everolimus)