Bortezomib and Lenalidomide in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00553644
First received: November 2, 2007
Last updated: August 13, 2015
Last verified: June 2015
  Purpose

This phase II trial studies how well bortezomib and lenalidomide work in treating patients with mantle cell lymphoma that has come back after a period of improvement (refractory) or is not responding to treatment (refractory). Bortezomib may also stop the growth of cancer cells by blocking some proteins needed for cell growth. Lenalidomide may stimulate the immune system to kill cancer cells and may also block the growth of new blood vessels necessary for cell growth. Giving bortezomib with lenalidomide may be an effective treatment for relapsed or refractory mantle cell lymphoma.


Condition Intervention Phase
Recurrent Mantle Cell Lymphoma
Drug: Bortezomib
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bortezomib (NSC #681239) + Lenalidomide (Revlimid™, CC-5013) (NSC #703813) for Relapsed/Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Participants With an Overall Response Defined as Complete Response and Partial Response [ Time Frame: Duration of treatment (assessed up to 6 years) ] [ Designated as safety issue: No ]

    Response is assessed by investigator according to International Working Group (IWG) criteria.

    A complete response requires disappearance of all evidence of disease. A partial response is a >/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.



Secondary Outcome Measures:
  • Incidence of Adverse Events [ Time Frame: Assessed up to 6 years ] [ Designated as safety issue: Yes ]
    Toxicity data will be summarized using frequency tables. The description and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting.

  • Time to Progression [ Time Frame: Assessed up to 6 years ] [ Designated as safety issue: No ]
    Analyzed using the Kaplan-Meier method.

  • Overall Survival [ Time Frame: Assessed up to 6 years ] [ Designated as safety issue: No ]
    Analyzed using the Kaplan-Meier method.


Enrollment: 53
Study Start Date: November 2007
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (bortezomib, lenalidomide)
Patients receive induction therapy comprising bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response as best response after completion of induction therapy receive maintenance therapy comprising bortezomib IV on days 1 and 8 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 6 years in the absence of disease progression or unacceptable toxicity.
Drug: Bortezomib
Given IV
Other Names:
  • [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
  • BORTEZOMIB
  • LDP 341
  • MLN341
  • PS-341
  • PS341
  • Velcade
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • LENALIDOMIDE
  • Revlimid

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the overall response (complete response [CR] and partial response [PR]) rate and the complete response (CR) rate to bortezomib + lenalidomide therapy in patients with relapsed or refractory mantle cell lymphoma.

SECONDARY OBJECTIVES:

I. To determine the time to progression after therapy with bortezomib + lenalidomide in patients with relapsed or refractory mantle cell lymphoma.

II. To determine the disease-free survival and overall survival after therapy with bortezomib + lenalidomide in patients with relapsed or refractory mantle cell lymphoma.

OUTLINE:

Patients receive induction therapy comprising bortezomib intravenously (IV) over 3-5 seconds on days 1, 4, 8, and 11 and lenalidomide orally (PO) once daily (QD) on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a complete or partial response as best response after completion of induction therapy receive maintenance therapy comprising bortezomib IV on days 1 and 8 and lenalidomide PO QD on days 1-14. Treatment repeats every 21 days for up to 6 years in the absence of disease progression or unacceptable toxicity.

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

  Eligibility

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

Inclusion Criteria:

  • Histologically documented mantle cell lymphoma, with the following immunophenotypic characteristics: cluster of differentiation (CD)5+, CD23-, cyclin D1+; this may be from an initial diagnostic biopsy, or one obtained at time of relapse

    • Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine needle aspirates are not acceptable
    • Failure to submit pathology specimens within 60 days of patient registration will be considered a major protocol violation
  • Institutional flow cytometry or immunohistochemistry must confirm CD5 antigen expression, lack of CD23 antigen expression, and expression of cyclin D1
  • Prior therapy with at least one regimen, which may have been single agent or multi-agent, and consisted of traditional cytotoxic agents and/or biologic agents; patient may not have received prior bortezomib or lenalidomide therapy; patient must have progressive disease or refractory disease following that initial regimen(s); refractory disease will be defined as stable disease (SD) or progressive disease (PD) as best response to prior therapy, or CR or PR as initial response followed by disease progression within 6 months
  • Prior autologous, but not allogeneic, stem cell transplant is allowed
  • No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease; maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent
  • No prior radioimmunotherapy within 12 months of study entry
  • No >= grade 3 peripheral neuropathy within a month prior to study entry
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable; any tumor mass > 1 cm by physical exam, computed tomography (CT), magnetic resonance imaging (MRI), or conventional radiograph is acceptable; lesions that are considered non-measurable include the following:

    • Bone lesions (lesions, if present, should be noted)
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis or pulmonis
    • Bone marrow (involvement by non-Hodgkin lymphoma should be noted)
  • No known central nervous system (CNS) involvement by lymphoma
  • Patients with human immunodeficiency virus (HIV) infection are eligible, provided they meet the following: CD4+ cell count > 350/mm^3; treatment sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3; no history of acquired immunodeficiency syndrome (AIDS)-defining conditions or other HIV-related illnesses; no concurrent zidovudine or stavudine
  • Non-pregnant and non-nursing; females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10-14 days prior to registration; further, they 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 starting lenalidomide; 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 successful vasectomy; a FCBP 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); all patients must be counseled by a trained counselor every 28 days about pregnancy precautions and risks of fetal exposure; documentation of counseling is required on Cancer and Leukemia Group B (CALGB) form S-041
  • Patients with a recent history (within 3 months of study entry) of deep vein thrombosis (DVT)/pulmonary embolism (PE) are not eligible; patients with a distant history (greater than 3 months before study entry) of DVT/PE are eligible, but must receive either prophylactic aspirin or low molecular weight heparin, unless contraindicated
  • Left ventricular ejection fraction (LVEF) >= 45% by multigated acquisition (MUGA) scan or echocardiogram
  • No New York Heart Association class III or class IV congestive heart failure at study entry
  • No myocardial infarction within the past 6 months of study entry
  • No known positivity for hepatitis A, B, or C
  • Absolute neutrophil count (ANC) >= 1,000/uL (>= 500/uL if marrow involvement)
  • Platelets >= 75,000/uL
  • Creatinine =< 1.5 x upper limit of normal (ULN) (unless attributable to non-Hodgkin's lymphoma) and estimated creatinine clearance >= 30 mL/min (patients on dialysis are not eligible)
  • Total bilirubin =< 2 x ULN (unless attributable to non-Hodgkin's lymphoma and Gilbert's disease)
  • Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative
  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: NCT00553644

  Show 73 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Vicki Morrison Alliance for Clinical Trials in Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00553644     History of Changes
Other Study ID Numbers: NCI-2009-00483, NCI-2009-00483, CDR0000573827, CALGB 50501, CALGB-50501, U10CA180821, U10CA031946
Study First Received: November 2, 2007
Results First Received: January 6, 2014
Last Updated: August 13, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bortezomib
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015