NCT00712582

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
96

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2008

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2008

Completed
7 days until next milestone

First Submitted

Initial submission to the registry

July 8, 2008

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 10, 2008

Completed
12.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 12, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 12, 2021

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 21, 2022

Completed
Last Updated

June 21, 2022

Status Verified

March 1, 2021

Enrollment Period

12.7 years

First QC Date

July 8, 2008

Results QC Date

January 21, 2022

Last Update Submit

May 23, 2022

Conditions

Keywords

Non-HodgkinLymphomaRituximabCyclophosphamideDoxorubicinVincristineifosfamideetoposidecarboplatinstem cell transplant08-026

Outcome Measures

Primary Outcomes (1)

  • 2-year PFS From the Start of Induction Therapy Conditional

    2-year PFS from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation.

    2 years

Secondary Outcomes (4)

  • Overall Survival at 1 Year

    1 year

  • Proliferation Marker [18F] Fluorothymidine (FLT) is Significantly Predictive of Progression Free Survival/PFS Via a Log Rank Test.

    Through study completion, up to 10 years

  • Proliferation Marker [18F] Fluorothymidine (FLT) Significantly Predictive of Overall Survival/OS Via a Log Rank Test.

    Through the completion of study, up to 10 years

  • To Determine the Role of CT Volumetric Analysis Compared to Standard Unidimensional CT in This Patient Population.

    conclusion of study

Study Arms (3)

Consolidation A

EXPERIMENTAL

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

Consolidation B

EXPERIMENTAL

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

Consolidation C

EXPERIMENTAL

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

Interventions

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.

Consolidation A

It consists of four drugs in a regimen called augmented RICE (augRICE). It is given every 3 weeks for 2 cycles.

Consolidation B

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.

Consolidation C

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +4 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

  • Bantilan KS, Smith AN, Maurer MJ, Teruya-Feldstein J, Matasar MJ, Moskowitz AJ, Straus DJ, Noy A, Palomba ML, Horwitz SM, Hamlin PA, Portlock CS, Cerhan JR, Habermann TM, Salles GA, Nowakowski GS, Moskowitz CH, Zelenetz AD. Matched control analysis suggests that R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared with R-CHOP. Blood Adv. 2024 May 14;8(9):2172-2181. doi: 10.1182/bloodadvances.2023011408.

Related Links

MeSH Terms

Conditions

Lymphoma, Non-HodgkinLymphoma

Interventions

EtoposideCarboplatinIfosfamideRituximabMitoxantroneCyclophosphamideCarmustine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsGlucosidesGlycosidesCarbohydratesCoordination ComplexesPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedPhosphoramidesOrganophosphorus CompoundsOxazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsAnthraquinonesAnthronesAnthracenesQuinonesNitrosourea CompoundsUreaAmidesNitroso Compounds

Results Point of Contact

Title
Dr. Andrew Zelenetz, MD, PhD
Organization
Memorial Sloan Kettering Cancer Center

Study Officials

  • Andrew Zelenetz, MD, PhD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2008

First Posted

July 10, 2008

Study Start

July 1, 2008

Primary Completion

March 12, 2021

Study Completion

March 12, 2021

Last Updated

June 21, 2022

Results First Posted

June 21, 2022

Record last verified: 2021-03

Locations