CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00109967
First received: May 3, 2005
Last updated: January 30, 2013
Last verified: November 2012
  Purpose

This phase II trial is studying how well giving CCI-779 together with rituximab works in treating patients with relapsed or refractory mantle cell lymphoma. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving CCI-779 together with rituximab may kill more cancer cells


Condition Intervention Phase
Recurrent Mantle Cell Lymphoma
Biological: rituximab
Drug: temsirolimus
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate (complete, partial, and unconfirmed) during the first 24 weeks of treatment as defined by the International Workshop criteria [ Time Frame: Not Provided ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Time to event analysis of response [ Time Frame: Not Provided ] [ Designated as safety issue: No ]
  • Toxicity as measured by NCI CTCAE v.3.0 [ Time Frame: Not Provided ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 73
Study Start Date: May 2005
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: temsirolimus
Given IV
Other Names:
  • CCI-779
  • cell cycle inhibitor 779
  • Torisel

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.

II. Determine the tolerability of this regimen in these patients. III. Determine adverse events in patients treated with this regimen.

SECONDARY OBJECTIVES:

I. Determine the time to disease progression and overall survival of patients treated with this regimen.

II. Determine the time to response and duration of response in patients treated with this regimen.

OUTLINE: Patients are stratified according to prior response to rituximab (sensitive [partial response (PR) or complete response (CR) that lasted ≥ 6 months after the last treatment with rituximab alone or in combination with chemotherapy] vs refractory [stable or progressive disease OR a PR or CR that lasted < 6 months after the last treatment with rituximab alone or in combination with chemotherapy]).

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive rituximab IV on days 1, 8, 15, and 22 of course 1 and on day 1 only of courses 3, 5, 7, 9, and 11. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of course 3, patients undergo reevaluation. Patients achieving a CR or an unconfirmed CR (CRu) receive 2 additional courses of treatment for a total of 5 courses. Patients achieving a PR or stable disease continue study treatment as outlined above for up to 12 courses. Patients achieving a PR or stable disease who subsequently achieve a CR or CRu between courses 3 and 10 receive 2 additional courses of treatment.

After completion of study treatment, patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year, 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 confirmed* mantle cell lymphoma (MCL)

    • Relapsed, refractory, or stable disease after prior treatment
    • Tumor must be cyclin D-1 by immunohistochemistry OR 11;14 translocation by fluorescent in situ hybridization or cytogenetics
  • Measurable disease, defined as ≥ 1 of the following:

    • Unidimensionally measurable lymph node or tumor mass ≥ 2 cm by CT scan or MRI
    • Splenic enlargement if spleen is palpable ≥ 3 cm below the left costal margin
    • Malignant lymphocytosis if absolute lymphocytic count ≥ 5,000 AND lymphocytes confirmed to be monoclonal by flow cytometry
  • No known CNS involvement (e.g., parenchymal mass or leptomeningeal involvement)
  • Performance status - ECOG 0-2
  • At least 3 months
  • No other concurrent treatment for MCL
  • Absolute neutrophil count ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Direct bilirubin < 1.5 times ULN
  • AST ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)
  • Creatinine ≤ 2 times ULN
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Cholesterol ≤ 350 mg/dL
  • Fasting triglycerides < 400 mg/dL
  • No known HIV positivity
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness
  • No other active malignancy requiring treatment OR that would preclude assessment of response to study drugs
  • Prior biologic response modifiers allowed
  • Prior immunotherapy allowed
  • Prior high-dose therapy with stem cell support (i.e., stem cell transplantation) allowed
  • No concurrent prophylactic growth factor to support neutrophils
  • Prior chemotherapy allowed
  • No other concurrent chemotherapy
  • No concurrent corticosteroids to induce an antitumor response

    • Concurrent corticosteroids (≤ 10 mg/day of prednisone or equivalent) for adrenal insufficiency or acute allergic reactions allowed
  • Prior radiotherapy allowed
  • No prior treatment with a mTOR inhibitor
  • No other concurrent investigational or commercial agents or therapies for MCL
  • No other concurrent immunosuppressive therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00109967

  Show 195 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Ansell North Central Cancer Treatment Group
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00109967     History of Changes
Other Study ID Numbers: NCI-2009-00644, N038H, U10CA025224, CDR0000425334
Study First Received: May 3, 2005
Last Updated: January 30, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Sirolimus
Everolimus
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Anti-Bacterial Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 21, 2013