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B-cell Adult Acute Lymphoblastic LeukemiaPhase 1/2NCT02281279

Rituximab, Romidepsin, and Lenalidomide in Treating Patients With Recurrent or Refractory B-cell Non-Hodgkin Lymphoma

A Phase 1/2 study testing rituximab, lenalidomide and romidepsin in people with B-cell Adult Acute Lymphoblastic Leukemia and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by Mayo Clinic.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of romidepsin and lenalidomide when combined with rituximab and to see how well this combination works in treating patients with B-cell non-Hodgkin lymphoma that has returned (recurrent) or did not respond to treatment (refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
rituximab, lenalidomide and romidepsin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Oct 2016to Oct 2020
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • PHASE I: Histological confirmation of relapsed (recurrent after previous therapy[ies]) or refractory (no response to previous therapy[ies]) B-cell NHL; note: patients with small lymphocytic lymphoma (SLL) are eligible however patients with chronic lymphocytic leukemia (CLL) are not eligible
  • PHASE II: Histological confirmation of transformation of FL lymphoma to diffuse large B cell lymphoma or aggressive lymphoma
  • The biopsy confirming diagnosis can be up to 12 weeks prior to registration as long as there is no intervening therapy; note: if patient has had lymphoma treatment since previous biopsy, a biopsy should be repeated
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
  • Measurable disease (at least 1 lesion of >= 1.5 cm in diameter) as detected by computed tomography (CT) or the CT images of the positron emission tomography (PET)/CT
  • Absolute neutrophil count (ANC) >= 1500/mm^3
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  • Platelet count >= 75,000/mm^3
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN, the direct bilirubin =< ULN
  • Alkaline phosphatase =< 3 x ULN unless due to direct lymphoma involvement, and then =< 5 x ULN
  • Aspartate transaminase (AST) =< 3 x ULN unless due to direct lymphoma involvement, and then =< 5x ULN
  • Calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault formula
  • Magnesium >= 1.6 mg/dL
  • Potassium >= 3.5 mg/dL
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid Risk Evaluation and Mitigation Strategy (REMS)® program
  • Willing to be registered into the mandatory Revlimid REMS® program, and willing and able to comply with the requirements of the REMS® program
  • If currently not on anticoagulation medication, willing and able to take aspirin (325 mg) daily; note: if aspirin is contraindicated, the patient may be considered for the study after if on therapeutic dose warfarin or low molecular weight heparin; patients unable to take any prophylaxis are not eligible
  • Life expectancy >= 3 months
  • Ability to complete medication diary by themselves or with assistance
  • Ability to provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Note: during the active monitoring phase of a study (i.e., active treatment and observation), participants must be willing to return to the consenting institution for follow-up
  • Willing to provide tissue for central review and blood samples for correlative research purposes

Who cannot join

  • Prior therapy with histone deacetylase (HDAC) inhibitors or immunomodulatory drugs (IMDs) (lenalidomide or thalidomide)
  • Any of the following:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy
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  • Prolongation of corrected QT interval of > 480 ms
  • Receiving any medications that prolong the corrected QT (QTc) and have a known risk for Torsades de pointes; note: providers should use caution with drugs with possible increased risk for Torsades de pointes; patient will be eligible if they can be taken off these medications prior to initiation of therapy and no less than 4 half-life of the medication
  • Receiving any medications or substances that are strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)
  • Use of the following strong inhibitors are prohibited =< 7 days prior to registration
  • Boceprevir (Victrelis™)
  • Clarithromycin (Biaxin®, Biaxin XL®)
  • Conivaptan (Vaprisol®)
  • Grapefruit juice
  • Indinavir (Crixivan®)
  • Itraconazole (Sporanox®)
  • Ketoconazole (Nizoral®)
  • Lopinavir/ritonavir (Kaletra®)
  • Mibefradil
  • Nefazodone (Serzone®)
  • Nelfinavir (Viracept®)
  • Posaconazole (Noxafil®)
  • Ritonavir (Norvir®)
  • Saquinavir (Invirase®)
  • Telaprevir (Incivek®)
  • Telithromycin (Ketek®)
  • Receiving any medications or substances that are inducers of CYP3A4
  • Use of the following inducers are prohibited =< 12 days prior to registration
  • Avasimibe
  • Bosentan (Tracleer®)
  • Carbamazepine (Carbatrol®, Epitol®, Equetro™, Tegretol®, Tegretol-XR®)
  • Efavirenz (Sustiva®)
  • Modafinil (Provigil®)
  • Phenobarbital (Luminal®)
  • Phenytoin (Dilantin®, Phenytek®)
  • Rifabutin (Mycobutin®)
  • Rifampin (Rifadin®)
  • St. John's wort
  • 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
  • Known positivity for human immunodeficiency virus (HIV); note: baseline testing for HIV is not required
  • Uncontrolled intercurrent illness 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; note: patients with hepatitis B and C are eligible at the discretion of the treating physician; appropriate counseling regarding the risks of rituximab should be provided
  • Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
  • Other active malignancy requiring therapy; exceptions: non-melanotic skin cancer or any cancer that in the judgment of the investigator will not interfere with treatment plan and response assessment; patients with >= 25% of the bone marrow radiated for other diseases are not eligible
  • History of myocardial infarction =< 6 months prior to registration, unstable angina, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • History of life threatening or recurrent thrombosis/embolism; patients may participate if they are on anticoagulation during the treatment
  • Receiving erythroid stimulating agents (erythropoietin [EPO]: Procrit, Aranesp)
  • History of allogeneic bone marrow or stem cell transplantation

About this study

Official title: A Phase I/II Trial of Romidepsin, Rituximab and Lenalidomide (R3) in Relapsed/Refractory B Cell Lymphomas Including Transformed Follicular Lymphoma

This phase I/II trial studies the side effects and best dose of romidepsin and lenalidomide when combined with rituximab and to see how well this combination works in treating patients with B-cell non-Hodgkin lymphoma that has returned (recurrent) or did not respond to treatment (refractory). Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Romidepsin and lenalidomide may stop the growth of cancer cells by blocking enzymes needed for cell growth. Giving rituximab together with romidepsin and lenalidomide may be a better treatment for B-cell non-Hodgkin lymphoma.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish the maximum tolerated dose (MTD) of the combination of romidepsin, rituximab and lenalidomide in patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). (Phase I) II. To assess the overall response rate (ORR) of this combination in patients with transformed follicular lymphoma (FL). (Phase II)

SECONDARY OBJECTIVES:

  1. To assess the toxicity and safety of romidepsin in combination with lenalidomide and rituximab.

II. To assess complete response rate (CR), progression free survival (PFS), and overall survival (OS) of this combination in patients with transformed FL.

TERTIARY OBJECTIVES:

  1. To assess the impact of B-cell leukemia/lymphoma 2 (BCL2) mutations on ORR among patients treated with this combination.

II. To assess the impact of BCL2 mutations on PFS among patients treated with this combination.

OUTLINE: This is a phase I, dose-escalation study of romidepsin and lenalidomide followed by a phase II study.

Patients receive rituximab intravenously (IV) over 90 minutes on day 1; romidepsin IV over 4 hours on either day 1, days 1 and 8, or days 1, 8, and 15; and lenalidomide orally (PO) on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Being tested
rituximab, lenalidomide, romidepsin, laboratory biomarker analysis
Medical subject headings
Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Immunoblastic, Lymphoma, Follicular

What participants receive

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

  • rituximabBiological

    Also called IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8

    Given IV

  • lenalidomideDrug

    Also called CC-5013, IMiD-1, Revlimid

    Given PO

  • romidepsinDrug

    Also called FK228, FR901228, Istodax

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT02281279
Study groupRoleWhat they receive
Treatment (rituximab, romidepsin, lenalidomide)ExperimentalPatients receive rituximab IV over 90 minutes on day 1; romidepsin IV over 4 hours on either day 1, days 1 and 8, or days 1, 8, and 15; and lenalidomide PO on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Receives: Biological: rituximab; Drug: lenalidomide; Drug: romidepsin; Other: laboratory biomarker analysis

What is being measured

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

  1. MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I)

    Measured: 28 days

  2. Overall response rate (Phase II)

    A success is defined as a CR or partial response (PR) noted as the objective status. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true success proportion will be calculated.

    Measured: Up to 5 years

Secondary outcomes (7)

  1. Adverse events profile, graded according to the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

    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.

    Measured: Up to 30 days post-treatment

  2. Toxicity profile, defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment (Phase I)

    Non-hematologic toxicities will be evaluated via the ordinal Common Terminology Criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading. Overall toxicity incidence as well as toxicity profiles by dose level, patient and tumor site will be explored and summarized. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

    Measured: Up to 30 days post-treatment

  3. Response profile, defined to be a CR or PR noted as the objective status (Phase I)

    Responses will be summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease in this patient population.

    Measured: Up to 5 years

  4. CR rate (Phase II)

    Will be estimated by the number of patients who achieve a CR divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true complete response rate will be calculated.

    Measured: Up to 5 years

  5. Survival time (Phase II)

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

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

  6. PFS (Phase II)

    The distribution of PFS will be estimated using the method of Kaplan-Meier.

    Measured: Time from registration to the earliest date of documentation of disease progression or death due to any cause, assessed up to 5 years

  7. Incidence of adverse events, graded according to the revised NCI CTCAE version 4.0 (Phase II)

    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.

    Measured: Up to 30 days post-treatment

Timeline

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

  1. First posted3 Nov 2014 (estimated)
  2. Study startOct 2016
  3. Primary completionOct 2020 (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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02281279
Sponsor's protocol ID
MC1288
Other IDs
NCI-2014-02186, RM-FOL-PI-0034, MC1288, P30CA015083
Status last verified
Aug 2016
First submitted
30 Oct 2014
Last updated
11 Aug 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing rituximab, lenalidomide and romidepsin in people with B-cell Adult Acute Lymphoblastic Leukemia and Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, run by Mayo Clinic.

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 22 inclusion and 47 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: withdrawn, as of the sponsor's last update on 11 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

MTD, defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of patients (at least 2 of a maximum of 6 new patients) (Phase I) (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT02281279.

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 11 Aug 2016.

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