Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: November 7, 2008
Last updated: June 17, 2012
Last verified: February 2012

RATIONALE: 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. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with cladribine and rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with cladribine and rituximab and to see how well it works in treating patients with newly diagnosed mantle cell lymphoma.

Condition Intervention Phase
Biological: rituximab
Drug: cladribine
Drug: temsirolimus
Genetic: cytogenetic analysis
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)

Resource links provided by NLM:

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

Primary Outcome Measures:
  • Maximum tolerated dose of temsirolimus (Phase I) [ Designated as safety issue: Yes ]
  • Number of dose limiting toxicity incidents as assessed by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
  • Proportion of complete tumor responses [ Designated as safety issue: No ]
  • Toxicity profile as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Progression-free survival [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Correlation of traditional lymphoma parameters as well as absolute lymphocyte count, serum free light chains, and PI3K pathway member expression with response [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: April 2009
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Detailed Description:



  • To assess the efficacy and safety of the combination of rituximab, cladribine, and temsirolimus in patients with newly diagnosed mantle cell lymphoma.
  • To determine the maximum tolerated dose of temsirolimus combined with a fixed dose and schedule of rituximab and cladribine in these patients. (Phase I)
  • To assess the efficacy of this regimen, in terms of proportion of complete responses in these patients. (Phase II)


  • To assess other measures of efficacy of this regimen, including progression-free survival, duration of response, and overall survival of these patients.
  • To assess the toxicity profile of this regimen in these patients.
  • To assess efficacy using traditional lymphoma parameters and absolute lymphocyte count.
  • To assess metabolic markers (i.e., hyperglycemia and hyperlipidemia) as markers of mTOR inhibition using the glucose and lipid measurements being performed in the clinical laboratory as part of routine care for these patients.
  • To correlate response in these patients with serum free light chains, single nucleotide polymorphisms in host immune genes, vitamin D metabolites, and PI3K pathway member expression.

OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a phase II study.

Patients receive rituximab IV on day 1 and cladribine IV over 2 hours on days 1-5. Patients then receive temsirolimus IV over 30 minutes on day 1; on days 1 and 15; on days 1, 8, and 15; or on days 1, 8, 15, and 22*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 6-15 or pegfilgrastim SC on day 6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Patients enrolled in phase II receive temsirolimus at the maximum tolerated dose determined in phase I following a fixed schedule in a 28-day course.

Blood and tissue samples are collected at baseline and after course 2 for laboratory correlative studies. Samples are analyzed for serum free light chains, single nucleotide polymorphisms in host immune genes, vitamin D metabolites by liquid chromatography/tandem mass spectrometry, clinical metabolic markers (i.e., hyperglycemia or hyperlipidemia) as markers of mTOR inhibition, and PI3K pathway member expression.

After completion of study treatment, patients are followed periodically for up to 5 years.


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


  • Histologically confirmed mantle cell lymphoma

    • Newly diagnosed disease
    • Excisional biopsy or adequate core needle biopsies allowed
    • Tumor must be cyclin D-1 positive by IHC or have evidence of a t(11;14) translocation by FISH or cytogenetics
  • Measurable or assessable disease, defined as ≥ 1 of the following:

    • A lymph node or tumor mass that is ≥ 2.0 cm in ≥ 1 dimension by PET/CT, CT, MRI, or plain radiograph imaging
    • Enlarged spleen that is palpable ≥ 3 cm below the left costal margin
    • Diffuse infiltration of an organ (e.g., stomach, bone marrow, peripheral blood, liver, lungs, or bowel) by lymphoma without a discrete mass (assessable only disease)
  • No known CNS involvement


  • ECOG performance status 0-3
  • Life expectancy ≥ 12 weeks
  • ANC ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Serum creatinine ≤ 2.0 mg/dL
  • Serum total bilirubin (or direct bilirubin if total is abnormal) normal with or without secondary liver involvement
  • SGOT ≤ 3 times upper limit of normal (ULN) (≤ 5 times ULN if there is liver involvement)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 12 months after completion of study treatment
  • Willing to return to NCCTG enrolling institution for follow-up
  • Willing to provide blood and tissue specimens as required by the protocol
  • Willing to abstain from eating grapefruit or drinking grapefruit juice
  • No active or uncontrolled infection
  • No cardiac conditions, including any of the following:

    • Uncontrolled high blood pressure
    • Unstable angina
    • Active congestive heart failure
    • Myocardial infarction within the past 6 months
    • Serious uncontrolled cardiac arrhythmia
  • No medical or psychiatric conditions which, in the opinion of the investigator, make the patient a poor risk for participation
  • No known HIV positivity
  • No other malignancy within the past 5 years except carcinoma in situ of the cervix, resected basal cell or squamous cell carcinoma of the skin, or prostate cancer that is in remission following a radical retropubic prostatectomy or radiation therapy
  • No known hypersensitivity to rituximab or its components, or to murine proteins


  • No prior therapy for mantle cell non-Hodgkin lymphoma, including radiation therapy

    • Patients may have undergone a splenectomy for diagnosis, cytopenia, or systematic splenomegaly
  • No prior mTOR inhibitor
  • At least 7 days since prior and no concurrent enzyme-inducing antiepileptic drugs (e.g., phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbital, or primidone)
  • At least 7 days since prior and no concurrent potent CYP3A4 inducer (e.g., rifampin, glucocorticoids at greater than adrenal replacement levels, or St. John's wort)
  • At least 7 days since prior and no concurrent strong CYP3A4 inhibitors
  • No planned autologous or allogeneic stem cell transplantation as part of initial therapy
  • No concurrent combination anti-retroviral therapy for HIV-positive patients
  • No other specific, concurrent treatment for prior cancer (other than hormonal therapy)
  • No concurrent glucocorticoid steroids or other immunosuppressive therapies

    • Concurrent corticosteroids allowed for treatment of adrenal insufficiency, acute allergic reactions, or as N078D 27 prophylaxis for infusion-related adverse events
  • No other concurrent investigational agent that would be considered treatment for the primary neoplasm
  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: NCT00787969

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Sponsors and Collaborators
North Central Cancer Treatment Group
Principal Investigator: David J. Inwards, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00787969     History of Changes
Other Study ID Numbers: CDR0000619329, NCCTG-N078D
Study First Received: November 7, 2008
Last Updated: June 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

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

ClinicalTrials.gov processed this record on October 21, 2014