R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma
Phase I/II, Open-Label Study of R-ICE (Rituximab-Ifosfamide-Carboplatin-Etoposide) With Lenalidomide (R2-ICE) in Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
3 other identifiers
interventional
30
1 country
12
Brief Summary
This phase I/II trial studies the side effects and best dose of lenalidomide when given together with rituximab-ifosfamide-carboplatin-etoposide (R-ICE) and to see how well they work in treating patients with diffuse large B-cell lymphoma that has returned after a period of improvement (relapsed) and that has not responded to previous treatment (refractory). Drugs used in chemotherapy, such as rituximab, ifosfamide, carboplatin, etoposide, and lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving lenalidomide with R-ICE may be a better treatment for patients with diffuse large B-cell lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started May 2016
Longer than P75 for phase_1
12 active sites
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
First Submitted
Initial submission to the registry
December 9, 2015
CompletedFirst Posted
Study publicly available on registry
December 11, 2015
CompletedStudy Start
First participant enrolled
May 20, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 24, 2021
CompletedResults Posted
Study results publicly available
July 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 20, 2025
CompletedJuly 1, 2024
June 1, 2024
5.4 years
December 9, 2015
March 20, 2024
June 27, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Overall Response Rate (Phase II)
Will be defined as a complete metabolic response or partial metabolic response. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.
At 42 days (after 2 courses) of treatment
Secondary Outcomes (3)
Proportion of Patients Proceeding to Stem Cell Transplant
At 42 days of treatment
Complete Metabolic Response Rate
Up to 5 years
Overall Survival
From registration to death due to any cause, assessed up to 5 years
Other Outcomes (6)
Histologic Subtype (Germinal Center B-cell-like Versus Activated B-cell-like Versus Unclassified Subtype)
Up to 5 years
Standardized Uptake Value
Up to 5 years
Anatomic Size Reduction
Up to 5 years
- +3 more other outcomes
Study Arms (1)
Treatment (R2-ICE)
EXPERIMENTALPatients receive lenalidomide PO daily on days 1-14, rituximab IV on day 1, ifosfamide IV over 24 hours on day 2, carboplatin IV over 1-2 hours on day 2, and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more cycles per physician discretion. After completion of 2 cycles of R2ICE treatment, patients achieving objective status of CMR, PMR or NMR may proceed to SCT during the event monitoring phase.
Interventions
Given IV
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Age \>= 18 years
- Phase I: Histological confirmation of expressing CD20 antigen as determined by pathology at the respective institution and central pathology review at Mayo Clinic Rochester; all types of B-cell lymphomas are allowed to participate; patients with primary mediastinal large B-cell (PMLBCL) or transformed lymphoma are allowed to participate
- Phase II: Histological confirmation of DLBCL expressing CD20 antigen as determined by pathology at the respective institution and central pathology review at Mayo Clinic Rochester; patients with primary mediastinal large B-cell (PMLBCL) or transformed lymphoma are not allowed to participate
- Measurable disease (at least 1 lesion \>= 1.5 cm in diameter) as detected by PET/CT
- Only 1 line of previous anti-lymphoma therapy is allowed and not currently receiving any other agent that would be considered as a treatment for the lymphoma; patients must be \>= 2 weeks from prior anti-lymphoma therapy; the use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
- Absolute neutrophil count (ANC) \>= 1500/mm\^3, obtained =\< 7 days prior to registration
- Platelet count \>= 75,000/mm\^3, obtained =\< 7 days prior to registration
- Total bilirubin =\< 2 x upper limit of normal (ULN) (unless related to lymphoma or Gilbert's disease) OR =\< 5 x ULN for subjects with documented or suspected Gilbert's disease, or related to involvement of the liver by the lymphoma, obtained =\< 7 days prior to registration
- Aspartate transaminase (AST) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x ULN unless evidence of the direct liver and/or bone involvement by lymphoma, then =\< 5 x ULN, obtained =\< 7 days prior to registration
- PHASE I: Subjects must have calculated creatinine clearance \>= 60 ml/min by Cockcroft-Gault formula, obtained =\< 7 days prior to registration
- PHASE II: Subjects must have calculated creatinine clearance \>= 30 ml/min by Cockcroft-Gault formula, obtained =\< 7 days prior to registration
- For women of childbearing potential only: Negative pregnancy test =\< 10-14 days prior to registration; NOTE: the patient must have an additional negative pregnancy test =\< 24 hours prior to receiving the initial prescription of lenalidomide, per requirements of the REVLIMID Risk Evaluation and Mitigation Strategies (REMS) program
- Provide informed written consent
- Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study \[i.e. active treatment and observation\])
- +5 more criteria
You may not qualify if:
- Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception
- NOTE: patients unwilling or unable to do any of the following are also excluded:
- Men must agree to use a latex condom during sexual contact with a female of child-bearing potential even if they have had a successful vasectomy
- Women of child bearing potential must agree to use 2 methods of reliable contraception simultaneously
- All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy; NOTE: patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial; patients with HIV on antiretroviral therapy other than zidovudine (AZT) and/or stavudine and without prior acquired immunodeficiency syndrome (AIDS) defining conditions and adequate CD4 count (\> 400) are eligible
- History of myocardial infarction =\< 180 days prior to registration or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
- Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm; patients must be \>= 2 weeks from prior anti-lymphoma therapy; the use of steroids and/or rituximab up to 1 week prior to registration for management of symptoms is allowed
- Other active malignancy =\< 3 years prior to registration; EXCEPTIONS: non-melanotic skin cancer, carcinoma-in-situ of the cervix, or any cancer that, in the judgment of the investigator, has been treated with curative intent and will not interfere with the study treatment plan and response assessment; NOTE: if there is a history of prior malignancy, they must not be receiving other specific treatment such as radiation, chemotherapy, or immunotherapy for their cancer
- Unable or unwilling to take any prophylaxis; patients with history of or new/active deep vein thrombosis/embolism/thrombophilia are allowed to participate if they are on appropriate therapeutic anticoagulation during the treatment on the trial; these patients would not need the aspirin with the lenalidomide unless clinically indicated; therefore, patients must be able and willing to receive anticoagulation (prophylaxis versus therapeutic as clinically indicated)
- History of radiation therapy to \>= 25% of the bone marrow for other diseases
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (12)
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Carle Cancer Center NCI Community Oncology Research Program
Urbana, Illinois, 61801, United States
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, 56303, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
Rapid City Regional Hospital
Rapid City, South Dakota, 57701, United States
Marshfield Medical Center-Marshfield
Marshfield, Wisconsin, 54449, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr Grzegorz S. Nowakowski
- Organization
- Accru
Study Officials
- PRINCIPAL INVESTIGATOR
Grzegorz S Nowakowski
Academic and Community Cancer Research United
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 9, 2015
First Posted
December 11, 2015
Study Start
May 20, 2016
Primary Completion
September 24, 2021
Study Completion
December 20, 2025
Last Updated
July 1, 2024
Results First Posted
July 1, 2024
Record last verified: 2024-06