R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02628405|
Recruitment Status : Recruiting
First Posted : December 11, 2015
Last Update Posted : July 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|CD20 Positive Recurrent B-Cell Non-Hodgkin Lymphoma Recurrent Diffuse Large B-Cell Lymphoma Recurrent Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma Recurrent Transformed Non-Hodgkin Lymphoma Refractory B-Cell Non-Hodgkin Lymphoma Refractory Diffuse Large B-Cell Lymphoma Refractory Primary Mediastinal (Thymic) Large B-Cell Cell Lymphoma Refractory Transformed Non-Hodgkin Lymphoma||Drug: Carboplatin Drug: Etoposide Drug: Ifosfamide Other: Laboratory Biomarker Analysis Drug: Lenalidomide Biological: Rituximab||Phase 1 Phase 2|
I. To assess the safety and maximum tolerated dose (MTD) of the addition of lenalidomide to the R-ICE chemoimmunotherapy regimen (lenalidomide-rituximab-ifosfamide-carboplatin-etoposide [R2ICE]) for the treatment of primary-refractory/first-relapse B-cell lymphoma. (Phase I) II. To determine if the addition of lenalidomide (based on dose determination from phase I) to the R-ICE chemoimmunotherapy regimen (R2-ICE) would lead to clinically meaningful improvement in the overall response rates (ORR) for patients with first-relapse/refractory diffuse large B-cell lymphoma (DLBCL). (Phase II)
I. To evaluate the effect of the addition of lenalidomide to RICE on the number (percentage) of patients proceeding to stem cell transplant (SCT).
II. To evaluate the effect of the addition of lenalidomide to RICE on other surrogate outcome measures including complete metabolic response (CMR) rate and overall survival.
III. To describe the toxicities associated with the addition of lenalidomide to the R-ICE chemoimmunotherapy regimen (R2ICE).
I. To evaluate ORR based on germinal center B-cell-like (GCB) versus non-GCB subtypes.
II. To evaluate ORR based on percent standardized uptake value (SUV) reduction and percent anatomic size reduction on interim positron emission tomography (PET)/computed tomography (CT) scans.
III. To evaluate ORR based on minimal residual disease (MRD) detection (positive versus [vs.] negative) and quantification after 2 cycles of treatment.
IV. Future tissue and blood based studies.
OUTLINE: This is a phase I, dose-escalation study of lenalidomide followed by a phase II study.
Patients receive lenalidomide orally (PO) daily on days 1-14, rituximab intravenously (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 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, partial metabolic response (PMR), or no metabolic response (NMR) may receive 2 more courses 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.
After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||63 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Actual Study Start Date :||May 20, 2016|
|Estimated Primary Completion Date :||May 20, 2020|
|Estimated Study Completion Date :||January 20, 2023|
Experimental: Treatment (R2-ICE)
Patients 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 courses in the absence of disease progression or unacceptable toxicity. Patients achieving CMR, PMR, or NMR may receive 2 more courses 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.
Other: Laboratory Biomarker Analysis
- Maximum tolerated dose defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients of the addition of lenalidomide to rituximab-ifosfamide-carboplatin-etoposide (Phase I) [ Time Frame: 21 days ]The number and severity of all adverse events (overall and by dose-level) will be tabulated and summarized in this patient population. The grade 3+ adverse events will also be described and summarized in a similar fashion. This will provide an indication of the level of tolerance for this treatment combination in this patient group.
- Toxicity profile defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment as measured by Common Terminology Criteria for Adverse Events version 4.0 (Phase I) [ Time Frame: Up to 30 days after completion of study treatment ]Overall toxicity incidence as well as toxicity profiles by dose level and patient will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.
- Overall response rate defined as a complete metabolic response or partial metabolic response (Phase II) [ Time Frame: At 42 days (after 2 courses) of treatment ]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.
- Percentage of patients proceeding to stem cell transplant [ Time Frame: At 42 days of treatment ]Estimated by the number of patients who proceed to transplant divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.
- Complete metabolic response rate [ Time Frame: Up to 5 years ]Estimated by the number of patients with an objective status of complete metabolic response divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete metabolic response rate will be calculated.
- Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 5 years ]Will be estimated using the method of Kaplan-Meier.
- Incidence of adverse events [ Time Frame: Up to 30 days after completion of study treatment ]The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
- Histologic subtype (germinal center B-cell-like versus activated B-cell-like versus unclassified subtype) [ Time Frame: Up to 5 years ]Evaluated by 2 methods: Hans algorithm by immunohistochemistry and gene expression profiling using nanostring technology. For each method, the relationship between overall response (responder versus non-responder) complete response rate and subtype will be evaluated using Chi-square tests (or Fisher?s exact test if the data in the contingency table is sparse).
- Standardized uptake value [ Time Frame: Up to 5 years ]Evaluated by calculating the percentage (%) standardized uptake value noted on interim positron emission tomography/computed tomography scan and correlated with the overall response (responder versus non-responder) by using a two sample t-test.
- Anatomic size reduction [ Time Frame: Up to 5 years ]Evaluated by calculating the percentage (%) anatomic size reduction noted on interim positron emission tomography/computed tomography scan and correlated with the overall response (responder versus non-responder) by using a two sample t-test.
- Minimum residual disease detection in blood [ Time Frame: Up to 5 years ]The correlation of minimal residual disease detection (positive versus negative) with overall response will be evaluated using Chi-square tests (or Fisher?s exact test if the data in the contingency table is sparse).
- Minimum residual disease blood level [ Time Frame: Up to 5 years ]The correlation of minimal residual disease quantification (responder versus non-responder) with overall response will be evaluated using two sample t-tests.
- Serum sample collected and stored for future and ongoing research [ Time Frame: Up to 5 years ]Some of the initial work for which this would be utilized would include but not limited to studying the serum free light chains, serum free deoxyribonucleic acid and the minimal residual disease. These measures will be summarized descriptively using medians and ranges (continuous measures) or frequencies (categorical measures).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02628405
|United States, Florida|
|Mayo Clinic in Florida||Recruiting|
|Jacksonville, Florida, United States, 32224-9980|
|Contact: Kathleen M. Burke 904-953-2000 Burke.Kathleen@mayo.edu|
|Principal Investigator: Han W. Tun|
|United States, Illinois|
|Peoria, Illinois, United States, 61615|
|Carle Cancer Center NCI Community Oncology Research Program||Recruiting|
|Urbana, Illinois, United States, 61801|
|Contact: Pauline Mbuvi 217-383-4085 Pauline.Mbuvi@Carle.com|
|Principal Investigator: Priyank P. Patel|
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Susan B. Butcher 319-467-5827 firstname.lastname@example.org|
|Principal Investigator: Umar Farooq|
|Siouxland Regional Cancer Center||Recruiting|
|Sioux City, Iowa, United States, 51101|
|Contact: Thomas S. Hoopingarner 712-252-9326 HoopingarnerT@jencc.com|
|Principal Investigator: Donald B. Wender|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Mayo Clinic Clinical Trials Office 855-776-0015|
|Principal Investigator: Grzegorz S. Nowakowski|
|Coborn Cancer Center at Saint Cloud Hospital||Recruiting|
|Saint Cloud, Minnesota, United States, 56303|
|Contact: Stacy St. Onge 320-229-4907 email@example.com|
|Principal Investigator: Donald J. Jurgens|
|Metro Minnesota Community Oncology Research Consortium||Recruiting|
|Saint Louis Park, Minnesota, United States, 55416|
|Contact: Elizabeth J. Wagner 952-992-1555 Elizabeth.firstname.lastname@example.org|
|Principal Investigator: Daniel M. Anderson|
|United States, Nebraska|
|University of Nebraska Medical Center||Withdrawn|
|Omaha, Nebraska, United States, 68198|
|United States, New Hampshire|
|Dartmouth Hitchcock Medical Center||Recruiting|
|Lebanon, New Hampshire, United States, 03756|
|Contact: Julie Gurnsey 603-653-3640 Julie.email@example.com|
|Principal Investigator: Frederick Lansigan|
|United States, New Jersey|
|Hackensack University Medical Center||Recruiting|
|Hackensack, New Jersey, United States, 07601|
|Contact: Kara M. Yannotti 551-996-5900 Kara.Yannotti@HackensackMeridian.org|
|Principal Investigator: Tatyana A. Feldman|
|United States, New York|
|State University of New York Upstate Medical University||Recruiting|
|Syracuse, New York, United States, 13210|
|Contact: Joanne M. Chilton 315-464-8240 firstname.lastname@example.org|
|Principal Investigator: Teresa C. Gentile|
|United States, Pennsylvania|
|Geisinger Medical Center||Withdrawn|
|Danville, Pennsylvania, United States, 17822|
|United States, South Dakota|
|Rapid City Regional Hospital||Completed|
|Rapid City, South Dakota, United States, 57701|
|United States, Wisconsin|
|Marshfield, Wisconsin, United States, 54449|
|Contact: Sheryl L. Mandel 715-389-4457 Mandel.Sheryl@mcrf.mfldclin.edu|
|Principal Investigator: Ali W. Bseiso|
|Principal Investigator:||Grzegorz Nowakowski||Academic and Community Cancer Research United|