RADCHOP: RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
Study Details
Study Description
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
- Primary objective
: To define the maximum tolerable dose
- Secondary objective
-
To evaluate the dose-limiting toxicity
-
To evaluate the pharmacokinetics of RAD001
-
Pharmacogenomic profiling
Phase II
- Primary objective
: To evaluate the overall response rate
- Secondary objective
-
To estimate the time to progression
-
To estimate overall survival
-
Pharmacogenomic profiling
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: 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 |
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
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
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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
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At least one measurable lesion
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ECOG PS 0-2
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Informed consent
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Age 20 to 70 years old
Exclusion Criteria:
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Prior radiation therapy or surgery within 4 weeks prior to study entry
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History of central nervous system (CNS) metastases
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Ongoing cardiac dysrhythmias of NCI CTCAE grade ≥2.
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Pregnancy or breastfeeding.
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Hepatitis B virus surface antigen positive
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Extranodal NK/T cell lymphoma
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Mycosis fungoides
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ALK-positive Anaplastic large cell lymphoma
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | National Cancer Center | Goyang-si | Kyoungki-do | Korea, Republic of | |
2 | Samsung Medical Center | Seoul | Korea, Republic of | 135710 | |
3 | Asan Medical Center | Seoul | Korea, Republic of | ||
4 | Korea Cancer Center Hospital | Seoul | Korea, Republic of | ||
5 | Yonsei Medical Center, Severance Hospital | Seoul | Korea, Republic of |
Sponsors and Collaborators
- Samsung Medical Center
- Asan Medical Center
- Yonsei University
- National Cancer Center, Korea
- Korea Cancer Center Hospital
Investigators
- Principal Investigator: Won Seog Kim, MD, PhD, Samsung Medical Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2010-01-001