Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

CCI-779 in Treating Patients With Mantle Cell Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	18 and over	NCI	NCCTG-N0186 N0186, NCT00033267

Objectives

1. Determine the objective responses in patients with previously treated mantle cell non-Hodgkin's lymphoma treated with CCI-779.
2. Determine the toxic effects of this drug in these patients.
3. Determine whether this drug inhibits cell proliferation pathways in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed mantle cell non-Hodgkin's lymphoma (MCL)



• Relapsed, refractory, or stable disease after prior chemotherapy, radiotherapy, or immunotherapy



• Unidimensionally measurable lymph node or lesion
  • At least 2.0 cm by CT scan or MRI OR at least 1.5 cm by physical exam
  • One of the following measurement parameters may be used:
    • Splenic enlargement may be used as a measurement parameter if spleen is palpable at least 3.0 cm across left costal margin
    • Malignant lymphocytosis may be used as a measurement parameter if absolute lymphocyte count is at least 5,000/mm³



• No known CNS involvement (parenchymal mass or leptomeningeal involvement)

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics
• Prior high-dose therapy with stem cell transplantation allowed
• At least 7 days since prior immunotherapy or other non-myelosuppressive biologic response modifiers

Chemotherapy:

• See Disease Characteristics
• See Biologic therapy
• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas or mitomycin)
• No other concurrent chemotherapy for MCL

Endocrine therapy:

• Concurrent corticosteroids for adrenal insufficiency allowed

Radiotherapy:

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy
• No concurrent radiotherapy for MCL

Surgery:

• Not specified

Other:

• Any number of prior treatments allowed
• No other concurrent investigational or commercial agents for MCL
• No concurrent drugs that induce cytochrome p450 (e.g., carbamazepine, phenobarbital, phenytoin, ketoconazole, diltiazem, rifampin, terfenadine, cisapride, astemizole, or pimozide)
• No concurrent immunosuppressive therapies

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
• Hemoglobin ≥ 8 g/dL

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 metastases are present)

Renal:

• Creatinine ≤ 2 times ULN

Cardiovascular:

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

Other:

• Cholesterol ≤ 350 mg/dL
• Triglycerides ≤ 400 mg/dL
• HIV negative
• No other active malignancy requiring treatment or that would preclude study participation
• No other concurrent uncontrolled illness
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after study participation

Expected Enrollment

A maximum of 27 patients will be accrued for this study within 2 years.

Outcomes

Overall response (complete and partial) during first 24 weeks of treatment

Time to progression
Overall survival
Progression-free survival
Duration of response

Outline

Patients receive CCI-779 IV over 30 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease receive a maximum of 6 courses. Patients with partial response receive a maximum of 12 courses. Patients with complete response (CR) receive 2 additional courses beyond CR.

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.

Ansell SM, Inwards DJ, Rowland KM Jr, et al.: Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer 113 (3): 508-14, 2008.[PUBMED Abstract]

Witzig TE, Ansell SM, Geyer SM, et al.: Anti-tumor activity of low-dose single agent CCI-779 for relapsed mantle cell lymphoma: a phase II trial in the North Central Cancer Treatment Group. [Abstract] J Clin Oncol 23 (Suppl 16): A-6504, 561s, 2005.

Witzig TE, Geyer SM, Ghobrial I, et al.: Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23 (23): 5347-56, 2005.[PUBMED Abstract]

Witzig T, Geyer S, Ghobrial I, et al.: Anti-tumor activity of single-agent CCI-779 for relapsed mantle cell lymphoma: a phase II trial in the North Central Cancer Treatment Group. [Abstract] Blood 104 (11): A-129, 2004.

Witzig TE, Geyer SM, Salim M, et al.: A phase II trial of the rapamycin analog CCI-779 in previously treated mantle cell non-Hodgkins lymphoma: interim analysis of 18 patients. [Abstract] Blood 102 (11 Pt 1): A-2374, 2003.

Trial Contact Information

Trial Lead Organizations

North Central Cancer Treatment Group

Stephen Ansell, MD, PhD, Protocol chair		Ph: 507-284-2511

Registry Information
Official Title		A Phase II Study of CCI-779 in Previously Treated Patients with Mantle Cell Non-Hodgkin's Lymphoma
Trial Start Date		2002-04-05
Trial Completion Date		2008-02-26
Registered in ClinicalTrials.gov		NCT00033267
Date Submitted to PDQ		2002-02-05
Information Last Verified		2005-09-02
NCI Grant/Contract Number		CA25224

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