Clinical trial NCT01198665: RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
Official title: A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Peripheral T Cell Lymphoma Unspecified
Anaplastic Large Cell Lymphoma, ALK-negative
Angioimmunoblastic T Cell Lymphoma
Cutaneous T Cell Lymphoma
Keywords: RAD001
chemotherpy
T cell lymphoma
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
Collaborators: name: Asan Medical Center
name: Yonsei University
name: National Cancer Center, Korea
name: Korea Cancer Center Hospital
First posted: 2010-09-10
Enrollment: 46
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: determination of the maximum tolerable dose and evaluation of response rate
timeFrame: Phase I for maximal tolerable dose and phase II for efficacy
Secondary outcomes:
measure: doe-limiting toxicity and pharmacogenomics
timeFrame: Phase I/II
Other outcomes:
Locations:
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Kyoungki-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei Medical Center, Severance Hospital
Study officials:
affiliation: Samsung Medical Center
name: Won Seog Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: