Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Genentech
Columbia University
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00712582
First received: July 8, 2008
Last updated: June 2, 2014
Last verified: June 2014
  Purpose

About 60% of patients with DLBCL can be cured with a chemotherapy program. It is called RCHOP-21 (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). It is given once every 3 weeks, for 18 weeks. Each three weeks is a cycle. Some factors predict that you may not be cured with R-CHOP-21. The most common ones are:

  • Stage - how much DLBCL, PMBL, or FL3B you have
  • LDH - a blood chemistry marker; and
  • Whether you can do your normal daily activities. (performance status) We think that the best way to cure more patients with poor risk factors is to add new treatment to R-CHOP. You will get different chemotherapy after 4 cycles. This type of treatment is called risk-adapted therapy.

Condition Intervention Phase
Non-Hodgkin's Lymphoma
Drug: Etoposide, carboplatin, ifosfamide
Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin
Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To determine the 2-year PFS and overall survival from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Obtain preliminary data on biodistribution, dosimetry and potential clinical usefulness of the proliferation marker [18F] fluorothymidine (FLT) in pts with diffuse large cell lymphoma, using combined (FDG-PET/CT). [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]
    the earliest the second scan can be obtained is the day after prednisone completion. FLT-PET scans will be done for the first 60 patients.

  • To determine the role of CT volumetric analysis compared to standard unidimensional CT in this patient population. [ Time Frame: conclusion of the study ] [ Designated as safety issue: No ]

Estimated Enrollment: 101
Study Start Date: July 2008
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Consolidation A

Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow.

Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is < 80% will receive 3 cycles of standard dose ICE Chemotherapy.

Drug: Etoposide, carboplatin, ifosfamide
Patients in consolidation A will receive three drugs in a regimen called ICE. You will have 3 cycles. Each new cycle begins 2 to 3 weeks after the last one.
Experimental: Consolidation B

Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow.

Patients whose disease is FDG-PET negative or patients whose FDG-PET scan is positive but repeat biopsy is negative and whose initial Ki-67 expression is ≥80% will receive 2 cycles of augmented RICE Chemotherapy (as per MSKCC protocol 03-075).

Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin
It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.
Experimental: Consolidation C

Induction: RR-CHOP-14 Chemotherapy for Three Cycles Each cycle lasts approximately 14 days. A total of 3 cycles of RR-CHOP-14 will be given. One cycle of CHOP will follow.

Consolidation C: Patients with biopsy proven disease after induction therapy. Patients whose bone marrow remain positive at interim restaging will have the option of getting an allogeneic[m3] stem cell transplant, in lieu of an ASCT, if they have an acceptable HLA match donor. The allogeneic[m4] stem cell transplant regimen will be decided by the MSK Bone Marrow Transplant Service.

Drug: Rituximab, Ifosfamide, Etoposide, Carboplatin, Stem Cell Collection, Mitoxantrone, Cyclophosphamide and etoposide, Carmustine

It consists of four drugs in a regimen called augRICE. It is given every 3 weeks for 2 cycles. After the rituximab on day 3, you will then be admitted to the hospital for 2 to 3 nights.

Part 2: Stem Cell Collection, Part 3: High dose chemoradiotherapy and stem cell transplant. Your doctor may want you to get radiation therapy. If so, it will start 2 weeks before the highdose chemotherapy. This regimen is called CBV-N chemotherapy. It is given by vein in the hospital.


  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of diffuse large B cell lymphoma, PMLBL, or follicular lymphoma grade 3B confirmed by the department of hematopathology at MSKCC: Patients with discordant bone marrow involvement (i.e. involvement by small cleaved cells or small lymphocytic lymphoma) are eligible.
  • Tumors express CD20 as determined by immunohistochemistry.

    o Ki-67 evaluation of tumor tissue

  • Patients must have stage III, or IV disease. Patients with IIX, disease must have at least one other age-adjusted IPI risk factor.

    • KPS ≤ 70
    • LDH > upper limit of normal
  • All patients must have FDG-PET avid (minimum SUV 2.5) measurable disease
  • Patients must have normal baseline cardiac function based upon echocardiogram or gated blood pool scan (MUGA) with an ejection fraction ≥ 50%
  • Patients must have a serum creatinine of ≤ 1.5 mg/dl; if creatinine >1.5 mg/dl creatinine clearance must be >60 ml/minute.
  • Patients must have ANC>1000/mcl and Platelets>50,000/mcl. If patient has cytopenias due to bone marrow involvement, these requirements are not applicable.
  • Patients must have a bilirubin level of < 2.0 mg/dl in the absence of a history of Gilbert's disease (or pattern consistent with Gilbert's)
  • Patients must be Hepatitis B surface antigen negative, Hepatitis B core antibody negative, and Hepatitis C negative.
  • All patients of childbearing and child creating age must be using an acceptable form of birth control from the initiation of treatment on study until 1 year after completion of chemotherapy and/or transplant.
  • Women who are pre-menopausal must have a negative pregnancy test
  • Age between 18 and 65
  • Patients must be HIV negative. This test may be pending in a patient without risk factors, as determined by the patient's physician.
  • If patients have a history of malignancy other than cutaneous basal cell or squamous cell carcinoma, they must be disease-free for ≥ 5 years at the time of enrollment.
  • Patients or their guardians must be capable of providing informed consent.
  • Patients must be suitable to undergo stem cell transplant.

Exclusion Criteria:

  • Any lymphoma subtype other than DLBCL, PMLBL, follicular lymphoma grade 3B
  • Patients with either parenchymal brain or lepto-meningeal involvement.
  • No more than 14 days of prednisone therapy between the diagnostic biopsy of either DLBCL, PMLBL, or follicular lymphoma grade 3B and the initiation of treatment on study.
  • Known pregnancy or breast-feeding
  • Medical illness unrelated to NHL which in the opinion of the attending physician and principal investigator will preclude administration of chemotherapy safely. This includes patients with uncontrolled infection, chronic renal insufficiency, myocardial infarction within the past 6 months, unstable angina, cardiac arrhythmias other than chronic atrial fibrillation and chronic active or persistent hepatitis, or New York Heart Association Classification III or IV heart disease.
  • History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix.
  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: NCT00712582

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genentech
Columbia University
Investigators
Principal Investigator: Craig Moskowitz, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00712582     History of Changes
Other Study ID Numbers: 08-026
Study First Received: July 8, 2008
Last Updated: June 2, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Non-Hodgkin
Lymphoma
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
ifosfamide
etoposide
carboplatin
stem cell transplant
08-026

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Etoposide phosphate
Isophosphamide mustard
Carboplatin
Cyclophosphamide
Etoposide
Mitoxantrone
Ifosfamide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on October 01, 2014