Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI	NCCTG-N038H N038H, NCT00109967

Objectives

Primary

1. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.
2. Determine the tolerability of this regimen in these patients.
3. Determine adverse events in patients treated with this regimen.

Secondary

1. Determine the time to disease progression and overall survival of patients treated with this regimen.
2. Determine the time to response and duration of response in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• 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

   [Note: *By peripheral blood flow cytometry and/or bone marrow aspirate and biopsy for patients who have had a prior excisional biopsy; patients who have had intervening treatment since last biopsy are required to have a rebiopsy]




• 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)

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• Prior chemotherapy allowed
• No other concurrent chemotherapy

Endocrine therapy

• 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

Radiotherapy

• Prior radiotherapy allowed

Surgery

• Not specified

Other

• No prior treatment with a mTOR inhibitor
• No other concurrent investigational or commercial agents or therapies for MCL
• No other concurrent immunosuppressive therapy
• No other concurrent treatment for MCL

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³

Hepatic

• Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

  OR

• Direct bilirubin < 1.5 times ULN
• AST ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)

Renal

• Creatinine ≤ 2 times ULN

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Other

• 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

Expected Enrollment

A total of 40-73 patients (24-45 in stratum 1 and 16-28 in stratum 2) will be accrued for this study within approximately 3 years.

Outcomes

Response rate (complete, partial, and unconfirmed) during the first 24 weeks of treatment as defined by the International Workshop criteria

Time to progression
Time to event analysis of response
Toxicity as measured by NCI CTCAE v.3.0

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.

Jazirehi AR, Vega MI, Chatterjee D, et al.: Inhibition of the Raf-MEK1/2-ERK1/2 signaling pathway, Bcl-xL down-regulation, and chemosensitization of non-Hodgkin's lymphoma B cells by Rituximab. Cancer Res 64 (19): 7117-26, 2004.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Stephen Ansell, MD, PhD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Scott Kaufmann, MD, PhD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Radha Rao, MD, Protocol co-chair		Ph: 712-252-0088

Registry Information
Official Title		A Phase II Study of CCI-779 in Combination with Rituximab in Patients with Relapsed or Refractory Mantle Cell Lymphoma
Trial Start Date		2005-05-06
Trial Completion Date		2008-05-05 (estimated)
Registered in ClinicalTrials.gov		NCT00109967
Date Submitted to PDQ		2005-03-07
Information Last Verified		2009-03-06
NCI Grant/Contract Number		CA25224

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