Study of Pomalidomide for Treatment of Relapsed/Refractory Primary Central Nervous System Lymphoma and Newly Diagnosed or Relapsed/Refractory Intraocular Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Mayo Clinic
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01722305
First received: November 2, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

This phase I clinical trial aims to elucidate the maximal tolerated dose and side effects of pomalidomide in patients with relapsed or refractory primary central nervous system lymphoma or newly diagnosed or relapsed or refractory vitreoretinal lymphoma (Intraocular lymphoma). The study will also determine the efficacy and survival related to pomalidomide therapy in a MTD expanded cohort.

Rationale - Pomalidomide is a novel immunomodulatory agent, which has shown significant activity against CNS lymphoma in preclinical studies. Blood brain barrier is an obstacle in treatment of brain tumors such as CNS lymphoma. Pomalidomide was shown to have an excellent CNS penetration in a murine model: approximately 39% of systemically administered pomalidomide could penetrate the central nervous system. As such, pomalidomide is a promising immunomodulator to be tested in a clinical trial for CNS lymphoma. It works by killing the lymphoma cells directly as well as indirectly via activation of the immune response against lymphoma cells.


Condition Intervention Phase
Primary Central Nervous System Lymphoma
Primary Vitreoretinal Lymphoma (Intraocular Lymphoma)
Drug: pomalidomide
Drug: dexamethasone
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 Patients With Newly Diagnosed or Relapsed/Refractory Primary Vitreoretinal Lymphoma

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of pomalidomide as 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 ]
    MTD is 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).


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Time from registration to progression or death due to PCNSL or PVRL lymphoma, assessed up to 1 year ] [ 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 1 year ] [ Designated as safety issue: No ]
    The distribution of overall survival will be estimated using the method of Kaplan-Meier.

  • Overall response rate [ Time Frame: upto one year ] [ Designated as safety issue: No ]
    The overall response rate 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.


Estimated Enrollment: 34
Study Start Date: April 2013
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pomalidomide, dexamethasone)

In phase I, dose-escalation study of pomalidomide will be performed to determine the maximal tolerated dose (MTD). The dose escalation schedule consists of different dose levels: 2 mg/day (level -1), 3 mg/day (level 1, starting dose level), 5 mg/day (level 2), 7 mg/day (level 3), 10 mg/day (level 4). Dose escalation is to be determined by dose limiting toxicity (DLT). In the MTD expanded cohort, the maximal tolerated dose of pomalidomide as determined by phase I will be used.

Patients receive pomalidomide orally (PO) on days 1-21 of each 28-day cycle. In the first and second cycles of treatment, pomalidomide is given with dexamethasone 40 mg PO on days 1, 8, 15, and 22. Pomalidomide alone is given after the second cycle of treatment. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: pomalidomide
Given PO
Other Name: CC-4047
Drug: dexamethasone
Given PO
Other Names:
  • Decadron
  • DXM

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of pomalidomide in patients with CNS lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate the efficacy (overall response rate) and safety of pomalidomide in patients with primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) in an MTD expanded cohort.

II. To evaluate overall survival and progression free survival.

Objectives of correlative research:

I. To study the pharmacokinetics of pomalidomide in the central nervous system.

II. To identify the predictive biomarkers for responsiveness to pomalidomide.

  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 measurable CNS lesion (>= 1 cm in largest dimension); NOTE: tissue biopsy is not absolutely necessary unless clinical findings strongly suggest other etiologies as per treating physician; initial diagnosis must be made by tissue biopsy.
  • Relapsed/refractory primary vitreoretinal DLBCL who also have a measureable CNS lesion >= 1 cm in largest dimension); NOTE: tissue biopsy requirement of the CNS lesion is as outlined in bullet above; ocular tissue biopsy is required if ophthalmologic examination findings indicate ocular relapse.
  • Newly diagnosed or relapsed/refractory primary vitreoretinal DLBCL with or without cerebrospinal fluid (CSF) involvement but without brain or spinal cord involvement; NOTE: ocular tissue biopsy is required for all cases as part of ophthalmologic examination; Note: these patients will be eligible for participation in MTD expanded phase of the study.
  • 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 childbearing potential (FCBP)Â must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting Pomalidomide and must either commit to continued 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; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
  • 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

Exclusion Criteria:

  • 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
  • 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: unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol
  • Persistent toxicities >= grade 2 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 Campus in Arizona Active, not recruiting
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic Campus in Florida Recruiting
Jacksonville, Florida, United States, 32224
Contact: Mayo Clinic Clinical Trials Referral Office    507-538-7623      
Principal Investigator: Han W. Tun, M.D.         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Mayo Clinic Clinical Trials Referral Office    507-538-7623      
Principal Investigator: Patrick B. Johnston, M.D.         
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Han W. Tun, M.D. 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
Study First Received: November 2, 2012
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents

ClinicalTrials.gov processed this record on July 29, 2014