Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)
Overview
- Phase
- Phase 1
- Intervention
- rituximab
- Conditions
- Lymphoma
- Sponsor
- Alliance for Clinical Trials in Oncology
- Enrollment
- 74
- Locations
- 144
- Primary Endpoint
- Number of dose limiting toxicity incidents as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0 (Phase I)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This phase I/II trial studies 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. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the efficacy and safety of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma. II. To determine the maximum tolerated dose (MTD) of temsirolimus combined with a fixed dose and schedule of rituximab and cladribine. (Phase I) III. To assess the efficacy of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma with the proportion of complete responses as the primary endpoint. (Phase II) SECONDARY OBJECTIVES: I. To assess other measures of efficacy of the regimen including progression free survival, duration of response, and overall survival. II. To assess the toxicity profile of the combination of rituximab, cladribine, and temsirolimus. III. To assess efficacy using traditional lymphoma parameters and absolute lymphocyte count. IV. To assess metabolic markers (hyperglycemia, hyperlipidemia) as markers of mammalian target of rapamycin (mTOR) inhibition using the glucose and lipid measurements being performed in the clinical laboratory as part of routine care. V. To correlate response with serum free light chains, single nucleotide polymorphisms (SNPs) in host immune genes, vitamin D metabolites, and phosphatidylinositide 3-kinase (PI3K) pathway member expression. VI. As part of ongoing research for North Central Cancer Treatment Group (NCCTG) lymphoma studies, paraffin-embedded tissue blocks/slides and blood products will be banked for future studies. OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a phase II study. Patients receive rituximab intravenously (IV) on day 1 and cladribine IV over 2 hours on days 1-5. Patients then receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive filgrastim 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. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 4 months for 3 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically confirmed mantle cell lymphoma (MCL); the diagnosis must be confirmed by NCCTG pre-registration pathology review by Dr. Paul Kurtin or his designate; it is recommended that the biopsy be an excisional biopsy, but adequate core-needle biopsies will be accepted as long as they are considered adequate for registration by Dr. Kurtin or his designate; the tumor must be cyclin D-1 positive by immunohistochemistry or have evidence of a t(11;14) translocation by fluorescence based in situ hybridization (FISH) or cytogenetics
- •Measurable or assessable disease, defined as at least one of the following:
- •A lymph node or tumor mass that is \>= 2.0 cm in at least one dimension by positron emission tomography (PET)/computed tomography (CT), CT, magnetic resonance imaging (MRI), or plain radiograph imaging
- •Splenic enlargement may be used as a measurable parameter if the spleen is palpable \>= 3 cm below the left costal margin
- •Diffuse infiltration of an organ such as the stomach, bone marrow, peripheral blood, liver, lungs, or bowel by lymphoma without a discrete mass would constitute assessable, but not measurable, disease
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, 2, or 3
- •Life expectancy \>= 12 weeks
- •Absolute neutrophil count (ANC) \>= 1,500/mm³
- •Platelet count (PLT) \>= 100,000/mm³
- •Serum creatinine =\< 2.0 mg/dL
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Intervention: rituximab
Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Intervention: cladribine
Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Intervention: temsirolimus
Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Intervention: Filgrastim
Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Intervention: Pegfilgrastim
Outcomes
Primary Outcomes
Number of dose limiting toxicity incidents as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0 (Phase I)
Time Frame: 28 days
Proportion of complete tumor responses defined as complete remission (CR) as the objective status (Phase II)
Time Frame: Up to 5 years
Secondary Outcomes
- Progression-free survival (PFS)(up to 5 years)
- Time to disease progression(up to 5 years)
- Survival time(Up to 5 years)
- Overall survival(up to 5 years)
- Duration of response, defined as date at which the patient's objective status is first noted to be either a CR or partial remission to the date progression is documented(Up to 5 years)
- Frequency and severity of adverse events assessed by CTCAE v3.0(Up to 5 years)