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Recurrent Nervous System LymphomaPhase 1NCT03798314

Nivolumab and Pomalidomide in Treating Patients With Relapsed or Refractory Central Nervous System Diffuse Large B Cell Lymphoma or Primary Vitreoretinal Diffuse Large B Cell Lymphoma

A Phase 1 study testing Nivolumab and Pomalidomide in people with Recurrent Nervous System Lymphoma and Recurrent Primary Vitreoretinal DLBCL, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trials studies side effects and best dose of pomalidomide when given together with nivolumab in treating patients with primary central nervous system diffuse large B cell lymphoma or primary vitreoretinal diffuse large B cell lymphoma that has come back or that has not responded to treatment. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab and Pomalidomide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
2 sitesUnited States
Study dates
30 Jan 2019to 15 Sep 2021
Phase
Phase 1
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

  • Patient must have one of the following:
  • Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a brain lesion >= 1 cm, or with cerebrospinal fluid (CSF) relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy
  • NOTE: Tissue biopsy is not absolutely necessary for brain tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician. Initial diagnosis must be made by tissue biopsy OR
  • Relapsed/refractory primary vitreoretinal diffuse large B cell lymphoma (DLBCL) with a CNS lesion >= 1 cm, or with CSF relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy. Relapsed PVRL must have progressed or failed at least one systemic regimen
  • NOTE: Intraocular treatments are not regarded as systemic therapy
  • NOTE: If recurrence in ocular or leptomeningeal space, the patient will need a positive ocular tissue biopsy and CSF biopsy. Tissue biopsy requirement of the CNS lesion is as outlined in bullet above
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  • Patient progressed after or did not respond to at least 1 line of systemic therapy (e.g., high-dose methotrexate, high-dose methotrexate based regimen, high dose cytarabine, etc)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
  • Absolute neutrophil count (ANC) >= 1500/mm^3 (within =< 14 days prior to registration)
  • Platelet count >= 100,000/mm^3 (within =< 14 days prior to registration)
  • Hemoglobin >= 9.0 g/dL (within =< 14 days prior to registration)
  • Direct bilirubin < 1.5 x upper limit of normal (ULN) (or total bilirubin =< 3.0 x ULN with direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert?s Syndrome) (within =< 14 days prior to registration)
  • Aspartate transaminase (AST) =< 3 x ULN (within =< 14 days prior to registration)
  • Creatinine =< 1.5 x ULN OR calculated creatinine clearance must be >= 45 ml/min using the Cockcroft-Gault formula (within =< 14 days prior to registration)
  • Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) =< 1.5 x ULN OR if patient is receiving anticoagulant therapy and PT or PTT is within therapeutic range of intended use of anticoagulants (within =< 14 days prior to registration)
  • Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/ml, =< 14 days prior to registration and within 24 hours of starting pomalidomide. In addition, must either commit to continue abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking pomalidomide. WOCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a WOCBP even if they have had a vasectomy. In addition, women of childbearing potential (WOCBP) receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of nivolumab. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of nivolumab. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • A woman of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Able to take aspirin (81 or 325 mg) daily or an anticoagulant (as determined by treating physician) as prophylactic anticoagulation
  • Provide written informed consent
  • Willingness to return to enrolling institution for follow-up (during the active monitoring phase of the study)
  • Willingness to undergo biopsy procedures, if deemed necessary by treating physician
  • Willing to be registered into a mandatory POMALYST REMS program, and willing and able to comply with the requirements of the POMALYST REMS program

Who cannot join

  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant women
  • Nursing women
  • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • 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
  • Immunocompromised patients and patients known to be human immunodeficiency virus (HIV) positive
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  • 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
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
  • Other active malignancy =< 3 years prior to registration
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
  • NOTE: If there is a history of prior malignancy, they must not have received immune checkpoint inhibitors or immunomodulatory therapy (IMiD) for their cancer
  • History of myocardial infarction =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Use of corticosteroid in the absence of cerebral edema
  • NOTE: If a corticosteroid is used, it should be used at the lowest dose possible for the shortest possible duration. Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of treatment assignment are excluded
  • EXCEPTIONS: Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease
  • Therapy with myelosuppressive chemotherapy or biologic therapy =< 21 days prior to registration with incomplete recovery of blood counts
  • Persistent toxicities >= grade 3 from prior chemotherapy or biological therapy regardless of interval since last treatment
  • History of thromboembolic episodes =< 3 months prior to registration
  • Active hepatitis B or C with uncontrolled disease
  • NOTE: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B core IgM antibody (HBcIgM Ab), Hepatitis B surface antigen (HBsAg) and Hepatitis C virus (HCV) Ab screen (Scrn) w/Reflex testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV infection
  • Inability to swallow or impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection) that would preclude use of oral medications
  • Major surgery =< 4 weeks prior to registration or have not recovered from side effects of such therapy
  • New York Heart Association classification III or IV
  • Patient received radiation alone previously
  • NOTE: Radiation therapy would not be regarded as a systemic therapy
  • EXCEPTION: Patients who have received systemic therapy followed by radiation would be eligible
  • PCNSL with systemic disease
  • Inability to undergo or have a magnetic resonance imaging (MRI) performed

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase I Clinical Trial for Evaluation of Nivolumab and Pomalidomide Combination for Relapsed/Refractory Primary Central Nervous System Lymphoma and Primary Vitreoretinal Lymphoma

This phase I trials studies side effects and best dose of pomalidomide when given together with nivolumab in treating patients with primary central nervous system diffuse large B cell lymphoma or primary vitreoretinal diffuse large B cell lymphoma that has come back or that has not responded to treatment. Immunotherapy with monoclonal antibodies, such as pomalidomide and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To establish the maximum tolerated dose (MTD) of pomalidomide which can be safely combined with the fixed dose schedule of nivolumab in patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL). (Phase I)

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR) and progression free survival (PFS) of nivolumab and pomalidomide combination in patients with relapsed/refractory PCNSL and PVRL.

OUTLINE: This is dose-escalation study of pomalidomide.

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and pomalidomide orally (PO) on days 1-14. Treatment repeats every 4 weeks until disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 weeks, then every 3 months for 4 years.

Being tested
Nivolumab, Pomalidomide

What participants receive

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

  • NivolumabBiological

    Also called BMS-936558, MDX-1106, NIVO, ONO-4538

    Given IV

  • PomalidomideDrug

    Also called 4-Aminothalidomide, Actimid, CC-4047, Imnovid

    Given PO

Study groups in NCT03798314
Study groupRoleWhat they receive
Treatment (nivolumab and pomalidomide)ExperimentalPatients receive nivolumab IV over 30 minutes on day 1 and pomalidomide PO on days 1-14. Treatment repeats every 4 weeks until disease progression or unacceptable toxicity.
Receives: Biological: Nivolumab; Drug: Pomalidomide

What is being measured

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

  1. Maximum-tolerated dose (MTD) of pomalidomide

    The MTD in this study will be 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).

    Measured: Up to 28 days

  2. Incidence of adverse events

    Will be evaluated by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of all adverse events will be tabulated and summarized in this patient population both overall and by dose level. The grade 3+ adverse events will also be described and summarized in a similar fashion.

    Measured: Up to 12 weeks following end of treatment.

  3. Percentage of Participants With Grade 3 or Higher Adverse Events Considered At Least Possibly Related to Treatment

    The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.

    Measured: Up to 12 weeks following end of treatment

Secondary outcomes (3)

  1. Overall response rate (ORR)

    Will be estimated by the number of patients with an objective status of complete response (CR), unconfirmed complete response (CRu), or partial response (PR) divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

    Measured: Up to 4 years

  2. Progression-free survival (PFS)

    Will be estimated using the method of Kaplan-Meier.

    Measured: From registration to progression or death due to primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL), assessed up to 4 years

  3. Incidence of adverse events

    Will be assessed by CTCAE version 5.0. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

    Measured: Up to 12 weeks following treatment

Timeline

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

  1. First posted9 Jan 2019
  2. Study start30 Jan 2019
  3. Primary completion30 Dec 2020
  4. Study completion15 Sep 2021

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03798314
Sponsor's protocol ID
MC178A
Other IDs
NCI-2018-03661, MC178A
Status last verified
Sep 2021
First submitted
2 Jan 2019
Last updated
6 Jan 2023
Results posted
No
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 study testing Nivolumab and Pomalidomide in people with Recurrent Nervous System Lymphoma and Recurrent Primary Vitreoretinal DLBCL, run by Mayo Clinic at 2 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 22 inclusion and 29 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: finished, as of the sponsor's last update on 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 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.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Maximum-tolerated dose (MTD) of pomalidomide (time frame: Up to 28 days). The study lists 3 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 NCT03798314.

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 6 Jan 2023.

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