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: May 7, 2014
Last verified: March 2014
  Purpose

Bortezomib and lenalidomide may stop the growth of mantle cell lymphoma by blocking blood flow to the cancer. Bortezomib may also stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving bortezomib together with lenalidomide may kill more cancer cells.


Condition Intervention Phase
Recurrent Mantle Cell Lymphoma
Drug: bortezomib
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 (antiangiogenesis therapy, enzyme inhibitor therapy)
Patients receive induction therapy comprising bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11 and lenalidomide PO once daily 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 once daily 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:
  • LDP 341
  • MLN341
  • VELCADE
Drug: lenalidomide
Given PO
Other Names:
  • CC-5013
  • IMiD-1
  • Revlimid

Detailed Description:

PRIMARY OBJECTIVES:

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

II. To determine the disease-free and overall survival after therapy with bortezomib + lenalidomide therapy 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 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 once daily 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 periodically.

  Eligibility

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

Inclusion Criteria:

  • Histologically confirmed mantle cell lymphoma meeting the following criteria:

    • Diagnosis confirmed by initial biopsy or at time of relapse

      • No bone marrow biopsy as sole means of diagnosis

        • May be used in conjunction with nodal biopsies
      • No fine needle aspirates
    • CD5-positive, CD23-negative, and cyclin D1-positive by flow cytometry or immunohistochemistry
  • Measurable disease, defined as any tumor mass > 1cm by physical examination, CT scan, MRI, or conventional radiograph

    • No nonmeasurable disease only, including any of the following:

      • Bone lesions (should be noted, if present)
      • Ascites
      • Pleural or pericardial effusion
      • Lymphangitis cutis or pulmonis
      • Bone marrow (involvement by non-Hodgkin lymphoma should be noted)
  • Received prior therapy with at least 1 regimen, which may have been single- or multi-agent, and consisted of traditional cytotoxic and/or biologic agents

    • Must have progressive or refractory disease following initial regimen

      • Refractory disease defined as stable or progressive disease as best response to prior therapy, or complete or partial response as initial response followed by disease progression within 6 months
  • No known CNS involvement by lymphoma
  • ECOG performance status 0-2
  • ANC ≥ 1,000/μL (≥ 500/μL if marrow involvement)
  • Platelet count ≥ 75,000/μL
  • Total bilirubin ≤ 2 times upper limit of normal (ULN) (unless attributable to Gilbert disease)
  • Creatinine ≤ 1.5 times ULN (unless attributable to non-Hodgkin lymphoma) AND estimated creatinine clearance ≥ 30 mL/min (patients on dialysis are not eligible)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile women must use effective double-barrier contraception during and for at least 28 days after completion of lenalidomide therapy
  • Men must use effective contraception during and for 28 days after completion of lenalidomide therapy, even if they have undergone a successful vasectomy
  • No peripheral neuropathy ≥ grade 3 within the past month
  • Patients with HIV infection are eligible, provided they meet the following criteria:

    • CD4-positive cell count > 350/mm^3
    • Must have treatment-sensitive HIV and, if on anti-HIV therapy, HIV viral load < 50 copies/mm^3
    • No history of AIDS-defining conditions or other HIV-related illnesses
    • No concurrent zidovudine or stavudine because of overlapping toxicities with protocol therapy
  • No deep vein thrombosis (DVT) and/or pulmonary embolism (PE) within the past 3 months * Patients with a distant history (> 3 months prior to study entry) of DVT/PE are eligible, provided they receive concurrent prophylactic aspirin or low molecular weight heparin, unless contraindicated
  • LVEF ≥ 45% by MUGA scan or ECHO
  • No New York Heart Association class III or IV congestive heart failure
  • No myocardial infarction within the past 6 months
  • No known positivity for hepatitis A, B, or C
  • No concurrent dexamethasone or other steroidal antiemetics
  • No concurrent hormones used as chemotherapy or other chemotherapeutic agents except for steroids given for adrenal failure (hormones administered for non-disease related conditions [e.g., insulin for diabetes or birth control pills])
  • No prior bortezomib or lenalidomide
  • Prior autologous stem cell transplantation (SCT) allowed

    • No prior allogeneic SCT allowed
  • No prior radioimmunotherapy within the past 12 months
  • More than 2 weeks since prior corticosteroids, except maintenance therapy for a non-malignant disease

    • Maintenance therapy dose may not exceed20 mg/day prednisone or equivalent
  • No other concurrent investigational or commercial agents or therapies for lymphoma
  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 74 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Vicki Morrison Cancer and Leukemia Group B
  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, CALGB-50501, P30CA014236, U10CA031946
Study First Received: November 2, 2007
Results First Received: January 6, 2014
Last Updated: May 7, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 22, 2014