Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2015 by Mayo Clinic
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01722305
First received: November 2, 2012
Last updated: April 22, 2015
Last verified: April 2015
  Purpose

This phase I trial studies the side effects and best dose of pomalidomide when given together with dexamethasone in treating patients with primary central nervous system lymphoma that has come back (relapsed) or does not respond to treatment (refractory) or intraocular lymphoma that is newly diagnosed, relapsed or refractory. Pomalidomide may stimulate the immune system to kill cancer cells. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving pomalidomide together with dexamethasone may kill more cancer cells.


Condition Intervention Phase
Central Nervous System Non-Hodgkin Lymphoma
Intraocular Lymphoma
Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System
Recurrent Adult Diffuse Large Cell Lymphoma
Retinal Lymphoma
Drug: Pomalidomide
Drug: Dexamethasone
Other: Pharmacological Study
Other: Laboratory Biomarker Analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Pomalidomide for Patients With Relapsed/Refractory Primary CNS Lymphoma and Primary Vitreoretinal Lymphoma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • MTD of pomalidomide when given in combination with dexamethasone determined by dose-limiting toxicities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
    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. 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.


Secondary Outcome Measures:
  • Overall response rate defined as number of patients with an objective status of complete response (CR), complete response/unconfirmed (Cru), or partial response (PR) divided by total number of evaluable patients [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

  • Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of progression-free survival will be estimated using the method of Kaplan-Meier.

  • Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  • Incidence of adverse events, graded according to CTCAE 4.0 [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns.

  • Pharmacokinetics of pomalidomide in the CNS [ Time Frame: Up to day 22 of course 1 ] [ Designated as safety issue: No ]
    Based on pomalidomide levels in blood and CSF at different time points, area under curve will be determined.

  • Predictive biomarkers for response to pomalidomide [ Time Frame: Up to day 21 of course 1 ] [ Designated as safety issue: No ]
    Correlation studies will be performed to identify predictive immune markers for response to pomalidomide. Immune cell counts and cytokine profile will be evaluated in blood and CSF at day 1 and day 21 of course 1. Values at each time point and changes after pomalidomide treatment will be both graphically and quantitatively summarized and explored. Wilcoxon rank sum test and Fisher's exact test will be utilized where appropriate to assess the relationships of these markers with response.


Estimated Enrollment: 34
Study Start Date: April 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pomalidomide, dexamethasone)
Patients receive pomalidomide PO on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: Pomalidomide
Given PO
Other Names:
  • Actimid
  • CC-4047
  • Pomalyst
Drug: Dexamethasone
Given PO
Other Name: DM
Other: Pharmacological Study
Optional correlative studies
Other Name: pharmacological studies
Other: Laboratory Biomarker Analysis
Optional correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of pomalidomide in combination with dexamethasone in patients with relapsed/refractory primary central nervous system lymphoma (PCNSL) or primary vitreoretinal lymphoma (PVRL).

SECONDARY OBJECTIVES:

I. To evaluate the efficacy (overall response rate) and safety of pomalidomide in combination with dexamethasone in patients with PCNSL and PVRL lymphoma in an MTD expanded cohort.

II. To evaluate overall survival and progression free survival.

TERTIARY OBJECTIVES:

I. To study the pharmacokinetics of pomalidomide in the central nervous system. II. To identify the predictive biomarkers for responsiveness to pomalidomide.

OUTLINE: This is a dose-escalation study of pomalidomide.

Patients receive pomalidomide orally (PO) on days 1-21 and dexamethasone PO on days 1, 8, 15, and 22 of courses 1 and 2. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed or refractory primary central nervous system (CNS) diffuse large B cell lymphoma (PCNSDLBCL) with a CNS lesion, 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 CNS tumor unless clinical and radiologic findings strongly suggest other etiologies as per treating physician; initial diagnosis must be made by tissue biopsy; Note: patients with B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma are also eligible for the protocol as long as they meet other criteria; patients with typical Burkitt lymphoma are not eligible
  • Relapsed/refractory primary vitreoretinal DLBCL with a CNS lesion, with CSF relapse with positive CSF cytology, or with ocular relapse with positive ocular tissue biopsy; Note: tissue biopsy requirement of the CNS lesion is as outlined in bullet above
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2 or 3
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelets (PLT) >= 100,000/uL
  • Total bilirubin =< 1.5 x upper limit of normal (ULN) or if total bilirubin is > 1.5 x ULN the direct bilirubin must be =< 1.5 x ULN (=< 0.45 mg/dL)
  • Aspartate aminotransferase (AST) =< 3 x ULN
  • Creatinine =< 2.5 x ULN
  • Females of reproductive potential must be willing to adhere to the scheduled pregnancy testing as required in the POMALYST REMS™ program
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to acetylsalicylic acid [ASA] may use warfarin or heparin)
  • Provide informed written consent
  • Willing to return to participating medical institutions for follow-up
  • Willing to provide tissue samples for correlative research purposes
  • Willing to be registered into the mandatory POMALYST REMS™ program, and willing and able to comply with the requirements of the POMALYST REMS™ program

Exclusion Criteria:

  • Any of the following

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs
  • Uncontrolled infection
  • Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration; Note: patient who have recovered from cytopenia related to previous treatment and meet criteria of this protocol
  • 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
  • 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)
  • Immunodeficiency states including human immunodeficiency virus (HIV) infection
  • 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 immunoglobulin M antibody (HBcIgM Ab), hepatitis B surface antigen (HBsAg) and hepatitis C antibody screen (HCV Ab 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 hepatitis B (HBV) infection
  • Active other malignancy requiring treatment that would interfere with the assessments of response of the lymphoma to protocol treatment
  • 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
  • Any severe and/or uncontrolled medical conditions or other conditions that, in the treating physician's opinion, could adversely impact their ability to participate in the study
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01722305

Locations
United States, Arizona
Mayo Clinic in Arizona Recruiting
Scottsdale, Arizona, United States, 85259
Contact: Clinical Trials Referral Office    855-776-0015      
Principal Investigator: Craig B. Reeder         
United States, Florida
Mayo Clinic in Florida Recruiting
Jacksonville, Florida, United States, 32224-9980
Contact: Clinical Trials Referrals Office    855-776-0015      
Principal Investigator: Han W. Tun         
United States, Massachusetts
Dana-Farber Harvard Cancer Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Patrick Y. Wen    617-632-2166    pwen@partners.org   
Principal Investigator: Patrick Y. Wen         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Referrals Office    855-776-0015      
Principal Investigator: Patrick B. Johnston         
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Christian Grommes    212-639-4058    grommesc@mskcc.org   
Principal Investigator: Christian Grommes         
United States, Virginia
University of Virginia Recruiting
Charlottesville, Virginia, United States, 22908
Contact: David Schiff    434-982-4415    DS4JD@hscmail.mcc.virginia.edu   
Principal Investigator: David Schiff         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Marc C. Chamberlain    206-288-6737    chambemc@u.washington.edu   
Principal Investigator: Marc C. Chamberlain         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Han Tun Mayo Clinic in Florida
  More Information

No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT01722305     History of Changes
Other Study ID Numbers: MC1281, NCI-2012-01948, Mod12-003419-17, MC1281, P30CA015083
Study First Received: November 2, 2012
Last Updated: April 22, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Intraocular Lymphoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Eye Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
BB 1101
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Pomalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 05, 2015