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

Sponsor
Samsung Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT01198665
Collaborator
Asan Medical Center (Other), Yonsei University (Other), National Cancer Center, Korea (Other), Korea Cancer Center Hospital (Other)
46
5
1
53
9.2
0.2

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

  1. Primary objective

: To define the maximum tolerable dose

  1. 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

  1. Secondary objective
  • To estimate the time to progression

  • To estimate overall survival

  • Pharmacogenomic profiling

Condition or Disease Intervention/Treatment Phase
  • Drug: RAD001 (Everolimus)
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

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas
Study Start Date :
Jul 1, 2010
Actual Primary Completion Date :
Dec 1, 2014
Actual Study Completion Date :
Dec 1, 2014

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:
  • Cytoxan, Doxorubicin, Vincristine, prednisolone
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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

    Ages Eligible for Study:
    20 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. At least one measurable lesion

    2. ECOG PS 0-2

    3. Informed consent

    4. 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

    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.
    Responsible Party:
    Kim, Seok Jin, Associate professor, Samsung Medical Center
    ClinicalTrials.gov Identifier:
    NCT01198665
    Other Study ID Numbers:
    • 2010-01-001
    First Posted:
    Sep 10, 2010
    Last Update Posted:
    Mar 3, 2015
    Last Verified:
    Mar 1, 2015

    Study Results

    No Results Posted as of Mar 3, 2015