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

This study has been completed.
Sponsor:
Collaborators:
Asan Medical Center
Yonsei University
National Cancer Center, Korea
Korea Cancer Center Hospital
Information provided by (Responsible Party):
Kim, Seok Jin, Samsung Medical Center
ClinicalTrials.gov Identifier:
NCT01198665
First received: September 8, 2010
Last updated: March 1, 2015
Last verified: March 2015
  Purpose

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

Condition Intervention Phase
Peripheral T Cell Lymphoma Unspecified
Anaplastic Large Cell Lymphoma, ALK-negative
Angioimmunoblastic T Cell Lymphoma
Cutaneous T Cell Lymphoma
Drug: RAD001 (Everolimus)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of RAD001 Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphomas

Resource links provided by NLM:


Further study details as provided by Samsung Medical Center:

Primary Outcome Measures:
  • determination of the maximum tolerable dose and evaluation of response rate [ Time Frame: Phase I for maximal tolerable dose and phase II for efficacy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • doe-limiting toxicity and pharmacogenomics [ Time Frame: Phase I/II ] [ Designated as safety issue: Yes ]

    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


Enrollment: 46
Study Start Date: July 2010
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cytoxan, Doxorubicin, Vincristine, prednisolone

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

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01198665

Locations
Korea, Republic of
National Cancer Center
Goyang-si, Kyoungki-do, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of
Korea Cancer Center Hospital
Seoul, Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of, 135710
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
  More Information

No publications provided

Responsible Party: Kim, Seok Jin, Associate professor, Samsung Medical Center
ClinicalTrials.gov Identifier: NCT01198665     History of Changes
Other Study ID Numbers: 2010-01-001
Study First Received: September 8, 2010
Last Updated: March 1, 2015
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Samsung Medical Center:
RAD001
chemotherpy
T cell lymphoma

Additional relevant MeSH terms:
Immunoblastic Lymphadenopathy
Lymphoma
Lymphoma, Large-Cell, Anaplastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Everolimus
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2015