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Recurrent B-Cell Non-Hodgkin LymphomaPhase 1/2NCT02628405

R-ICE and Lenalidomide in Treating Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma

A Phase 1/2 study testing Carboplatin, Etoposide and Ifosfamide in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by Academic and Community Cancer Research United at 12 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Carboplatin, Etoposide and Ifosfamide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
12 sitesUnited States
Study dates
20 May 2016to 20 Dec 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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])
  • Willing to provide blood samples for correlative research purposes
  • Considered transplant-eligible, as determined by the opinion of the investigator at the participating institution; the participating institution does not need to be a transplant center but patients can be referred to a transplant center if needed
  • Willing and able to register into and comply with the mandatory requirements of Celgene's REVLIMID REMS program
  • Females of reproductive potential are willing and able to adhere to the scheduled pregnancy testing as required by Celgene's REVLIMID REMS program
  • Willing and able to take aspirin (81 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or low molecular weight heparin)

Who cannot join

  • 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
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  • 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
  • Receiving erythroid stimulating agents (epoetin alfa [EPO]: Procrit, Aranesp)
  • Patients with active or prior central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells; NOTE: these patients are usually treated with CNS directed therapy; screening for cerebrospinal fluid (CSF)/CNS involvement is NOT required but can be performed per treating medical doctor (MD) discretion
  • Active hepatitis B as defined by seropositivity for hepatitis B surface antigen (HBsAg); subjects with positive hepatitis B core antibody titers and normal liver transaminases are allowed provided that antiviral prophylaxis is administered per institutional guidelines; NOTE: subjects with hepatitis C antibody will be eligible provided that they do not have elevated liver transaminases or other evidence of active hepatitis

Trial locations and contacts

12 sites in 1 country.

12 sites in 1 country

United States12 sites

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Rapid City Regional Hospital

    Rapid City, South Dakota, 57701

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Coborn Cancer Center at Saint Cloud Hospital

    Saint Cloud, Minnesota, 56303

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Siouxland Regional Cancer Center

    Sioux City, Iowa, 51101

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Carle Cancer Center NCI Community Oncology Research Program

    Urbana, Illinois, 61801

Other trials in United States

About this study

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)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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)

SECONDARY OBJECTIVES:

  1. 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).

CORRELATIVE RESEARCH OBJECTIVES:

  1. 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 cycles 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 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.

After completion of study treatment, patients are followed up every 3 months for 3 years and then every 6 months for 2 years.

Being tested
Carboplatin, Etoposide, Ifosfamide, Laboratory Biomarker Analysis, Lenalidomide
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • IfosfamideDrug

    Also called Asta Z 4942, Asta Z-4942, Cyfos, Holoxan

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • LenalidomideDrug

    Also called CC-5013, CC5013, CDC 501, Revlimid

    Given PO

  • RituximabBiological

    Also called ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody

    Given IV

Study groups in NCT02628405
Study groupRoleWhat they receive
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.
Receives: Drug: Carboplatin; Drug: Etoposide; Drug: Ifosfamide; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Biological: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 42 days (after 2 courses) of treatment

Secondary outcomes (3)

  1. Proportion of Patients Proceeding to Stem Cell Transplant

    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.

    Measured: At 42 days of treatment

  2. Complete Metabolic Response Rate

    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.

    Measured: Up to 5 years

  3. Overall Survival

    The percentage of participants alive will be estimated using the method of Kaplan-Meier.

    Measured: From registration to death due to any cause, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2015 (estimated)
  2. Study start20 May 2016
  3. Primary completion24 Sep 2021
  4. Study completion20 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02628405
Sponsor's protocol ID
RU051417I
Other IDs
NCI-2015-01990, RU051417I, P30CA015083
Status last verified
Jun 2024
First submitted
9 Dec 2015
Last updated
1 Jul 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carboplatin, Etoposide and Ifosfamide in people with Recurrent B-Cell Non-Hodgkin Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by Academic and Community Cancer Research United at 12 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 1 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (Phase II) (time frame: At 42 days (after 2 courses) of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02628405.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2024.

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