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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00109967
First received: May 3, 2005
Last updated: December 3, 2013
Last verified: December 2013

May 3, 2005
December 3, 2013
May 2005
September 2009   (final data collection date for primary outcome measure)
Response Rate (Complete, Partial, and Unconfirmed) as Defined by the International Workshop Criteria [ Time Frame: Up to 12, 28-day cycles. ] [ Designated as safety issue: No ]

Complete Response (CR) - Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms.

Partial Response (PR) requires a >=50% decrease in sum of the products of the greatest dimension (SPD) of the six largest dominant nodes or nodal masses.

Not Provided
Complete list of historical versions of study NCT00109967 on ClinicalTrials.gov Archive Site
  • Time to Progression [ Time Frame: Patients were followed up to five years after registration. ] [ Designated as safety issue: No ]
    Time to progression was defined as the time from registration to the date of progression. Patients who died without disease progression were censored at the date of their last evaluation. Patients who were still receiving treatment at the time of these analyses were censored at the date of their last evaluation. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
  • Duration of Response [ Time Frame: Response duration is followed up to 5 years from registration. ] [ Designated as safety issue: No ]
    Duration of response was defined as the time from the date of documented response to the date of progression. Patients who went off treatment due to other reasons (eg, adverse reactions, refusal of further treatment) were censored at that time. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
  • Toxicity [ Time Frame: Assessed during treatment (up to 12, 28-day cycles) ] [ Designated as safety issue: Yes ]
    As per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3, toxicity was defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment by the treating physician.
  • Overall Survival [ Time Frame: Patients were followed for survival status for up to 5 years. ] [ Designated as safety issue: No ]
    Overall survival (OS) was defined as the time from registration to death resulting from any cause. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
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CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma

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

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 by assessing toxicity.

SECONDARY OBJECTIVES:

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

II. Determine the 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.

Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Mantle Cell Lymphoma
  • Biological: rituximab
    375 mg/m^2 Given IV
    Other Names:
    • IDEC-C2B8
    • IDEC-C2B8 monoclonal antibody
    • Mabthera
    • MOAB IDEC-C2B8
    • Rituxan
  • Drug: temsirolimus
    25 mg given IV
    Other Names:
    • CCI-779
    • cell cycle inhibitor 779
    • Torisel
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.
Interventions:
  • Biological: rituximab
  • Drug: temsirolimus
Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, Erlichman C, Witzig TE. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol. 2011 Apr;12(4):361-8. doi: 10.1016/S1470-2045(11)70062-6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
71
April 2011
September 2009   (final data collection date for primary outcome measure)

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 central nervous system involvement (e.g., parenchymal mass or leptomeningeal involvement)
  • Performance status - Eastern Cooperative Oncology Group (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
  • Aspartate aminotransferase (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 mammalian target of rapamycin (mTOR) inhibitor
  • No other concurrent investigational or commercial agents or therapies for MCL
  • No other concurrent immunosuppressive therapy
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00109967
NCI-2009-00644, N038H, U10CA025224, CDR0000425334
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Stephen Ansell North Central Cancer Treatment Group
National Cancer Institute (NCI)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP