Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: rituximabBiological: FilgrastimBiological: Pegfilgrastim
- Registration Number
- NCT00787969
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 74
-
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
-
Serum total bilirubin (or direct bilirubin if total is abnormal) =< institutional upper limit of normal (ULN) with or without secondary liver involvement
-
Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x institutional ULN (exception: if there is liver involvement, SGOT must be =< 5 x institutional ULN)
-
Negative pregnancy test done =< 7 days prior to registration, for women of childbearing potential only
-
Willingness to return to NCCTG enrolling institution for follow-up
-
Willingness to provide the blood specimens as required by the protocol
-
Willingness to provide tissue specimens as required by the protocol
-
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
-
Willingness to abstain from eating grapefruit or drinking grapefruit juice for the duration of the study
Exclusion Criteria
-
Any prior therapy for mantle cell non-Hodgkin lymphoma including radiation therapy; exception: patient may have undergone a splenectomy for diagnosis, cytopenia, or systematic splenomegaly
-
Active or uncontrolled infection
-
Any of the following cardiac conditions:
- Uncontrolled high blood pressure
- Unstable angina
- Active congestive heart failure
- Myocardial infarction =< 6 months
- Serious uncontrolled cardiac arrhythmia
-
Known central nervous system (CNS) involvement
-
Any of the following:
- Pregnant women or women of reproductive ability who are unwilling to use effective contraception while taking the drug and for 12 months after stopping treatment
- Nursing women
- Men who are unwilling to use a condom (even if they have undergone a prior vasectomy) while having intercourse with any woman, while taking the drug and for 12 months after stopping treatment
-
Medical or psychiatric conditions which, in the opinion of the investigator, make the patient a poor risk for participation
-
Known to be human immunodeficiency virus (HIV) positive; HIV testing is not required but should be done if clinically indicated; HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study
-
Concurrent malignancy =< 5 years ago; exceptions: carcinoma in situ of the cervix, resected basal cell or squamous cell carcinomas of the skin, or prostate cancer that is in remission following a radical retropubic prostatectomy or radiation therapy; if there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer
-
Known hypersensitivity to rituximab or its components, or to murine proteins
-
Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
-
Prior treatment with an mTOR inhibitor
-
Autologous or allogeneic stem cell transplant planned as part of initial therapy
-
Receiving enzyme-inducing antiepileptic drugs (enzyme inducing anti-epileptic drugs [EIAEDs]; e.g., phenytoin, fosphenytoin, carbamazepine, oxcarbazepine, phenobarbital, or primidone); any other potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin, glucocorticoids at greater than adrenal replacement levels, or St. John's wort; or receiving strong CYP3A4 inhibitors * Note: if these agents are discontinued, temsirolimus therapy can begin >= 7 days after discontinuation of such agent
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (rituximab, cladribine, temsirolimus) rituximab 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. Treatment (rituximab, cladribine, temsirolimus) Pegfilgrastim 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. Treatment (rituximab, cladribine, temsirolimus) Filgrastim 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. Treatment (rituximab, cladribine, temsirolimus) cladribine 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. Treatment (rituximab, cladribine, temsirolimus) 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.
- Primary Outcome Measures
Name Time Method 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) 28 days Proportion of complete tumor responses defined as complete remission (CR) as the objective status (Phase II) Up to 5 years
- Secondary Outcome Measures
Name Time Method 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
Trial Locations
- Locations (144)
Elkhart General Hospital
🇺🇸Elkhart, Indiana, United States
Bismarck Cancer Center
🇺🇸Bismarck, North Dakota, United States
St. Alexius Medical Center Cancer Center
🇺🇸Bismarck, North Dakota, United States
Mayo Clinic Scottsdale
🇺🇸Scottsdale, Arizona, United States
St. Mary's Hospital Medical Center - Green Bay
🇺🇸Green Bay, Wisconsin, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Holy Family Memorial Medical Center Cancer Care Center
🇺🇸Manitowoc, Wisconsin, United States
Green Bay Oncology, Limited at St. Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
Illinois CancerCare - Galesburg
🇺🇸Galesburg, Illinois, United States
Illinois CancerCare - Macomb
🇺🇸Macomb, Illinois, United States
Illinois CancerCare - Monmouth
🇺🇸Monmouth, Illinois, United States
Eureka Community Hospital
🇺🇸Eureka, Illinois, United States
CCOP - Northern Indiana CR Consortium
🇺🇸South Bend, Indiana, United States
BroMenn Regional Medical Center
🇺🇸Normal, Illinois, United States
Illinois CancerCare - Community Cancer Center
🇺🇸Normal, Illinois, United States
Community Hospital of Ottawa
🇺🇸Ottawa, Illinois, United States
Michiana Hematology-Oncology, PC - South Bend
🇺🇸Mishawaka, Indiana, United States
McDonough District Hospital
🇺🇸Macomb, Illinois, United States
Illinois CancerCare - Peru
🇺🇸Peru, Illinois, United States
Illinois CancerCare - Kewanee Clinic
🇺🇸Kewanee, Illinois, United States
Community Cancer Center
🇺🇸Normal, Illinois, United States
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸Pekin, Illinois, United States
St. Joseph Medical Center
🇺🇸Bloomington, Illinois, United States
Illinois CancerCare - Canton
🇺🇸Canton, Illinois, United States
Illinois CancerCare - Havana
🇺🇸Havana, Illinois, United States
Illinois CancerCare - Spring Valley
🇺🇸Spring Valley, Illinois, United States
Michiana Hematology Oncology PC - Plymouth
🇺🇸Plymouth, Indiana, United States
Galesburg Clinic, PC
🇺🇸Galesburg, Illinois, United States
OSF Holy Family Medical Center
🇺🇸Monmouth, Illinois, United States
Illinois CancerCare - Pekin
🇺🇸Pekin, Illinois, United States
Proctor Hospital
🇺🇸Peoria, Illinois, United States
Perry Memorial Hospital
🇺🇸Princeton, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸Ottawa, Illinois, United States
Center for Cancer Therapy at LaPorte Hospital and Health Services
🇺🇸La Porte, Indiana, United States
Cedar Rapids Oncology Associates
🇺🇸Cedar Rapids, Iowa, United States
Northern Montana Hospital
🇺🇸Havre, Montana, United States
CCOP - Montana Cancer Consortium
🇺🇸Billings, Montana, United States
Billings Clinic - Downtown
🇺🇸Billings, Montana, United States
Green Bay Oncology, Limited - Sturgeon Bay
🇺🇸Sturgeon Bay, Wisconsin, United States
St. James Healthcare Cancer Care
🇺🇸Butte, Montana, United States
Kalispell Medical Oncology at KRMC
🇺🇸Kalispell, Montana, United States
Bay Area Cancer Care Center at Bay Area Medical Center
🇺🇸Marinette, Wisconsin, United States
Bozeman Deaconess Cancer Center
🇺🇸Bozeman, Montana, United States
St. Peter's Hospital
🇺🇸Helena, Montana, United States
Glacier Oncology, PLLC
🇺🇸Kalispell, Montana, United States
Kalispell Regional Medical Center
🇺🇸Kalispell, Montana, United States
St. Vincent Healthcare Cancer Care Services
🇺🇸Billings, Montana, United States
Great Falls Clinic - Main Facility
🇺🇸Great Falls, Montana, United States
Regions Hospital Cancer Care Center
🇺🇸Saint Paul, Minnesota, United States
Hennepin County Medical Center - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
Park Nicollet Cancer Center
🇺🇸Saint Louis Park, Minnesota, United States
Mercy and Unity Cancer Center at Mercy Hospital
🇺🇸Coon Rapids, Minnesota, United States
Humphrey Cancer Center at North Memorial Outpatient Center
🇺🇸Robbinsdale, Minnesota, United States
Cancer Center of Kansas - Fort Scott
🇺🇸Fort Scott, Kansas, United States
HealthEast Cancer Care at St. John's Hospital
🇺🇸Maplewood, Minnesota, United States
Mercy and Unity Cancer Center at Unity Hospital
🇺🇸Fridley, Minnesota, United States
St. Francis Cancer Center at St. Francis Medical Center
🇺🇸Shakopee, Minnesota, United States
Welch Cancer Center at Sheridan Memorial Hospital
🇺🇸Sheridan, Wyoming, United States
Mid Dakota Clinic, PC
🇺🇸Bismarck, North Dakota, United States
Miller - Dwan Medical Center
🇺🇸Duluth, Minnesota, United States
Minnesota Oncology Hematology, PA - Maplewood
🇺🇸Maplewood, Minnesota, United States
CCOP - Duluth
🇺🇸Duluth, Minnesota, United States
Fairview Ridges Hospital
🇺🇸Burnsville, Minnesota, United States
Hutchinson Area Health Care
🇺🇸Hutchinson, Minnesota, United States
Cancer Center of Kansas, PA - Dodge City
🇺🇸Dodge City, Kansas, United States
Illinois Valley Community Hospital
🇺🇸Peru, Illinois, United States
Michiana Hematology Oncology PC - La Porte
🇺🇸Westville, Indiana, United States
CCOP - Illinois Oncology Research Association
🇺🇸Peoria, Illinois, United States
Howard Community Hospital
🇺🇸Kokomo, Indiana, United States
Saint Joseph Regional Medical Center
🇺🇸Mishawaka, Indiana, United States
Mercy Regional Cancer Center at Mercy Medical Center
🇺🇸Cedar Rapids, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - Des Moines
🇺🇸Des Moines, Iowa, United States
CCOP - Iowa Oncology Research Association
🇺🇸Des Moines, Iowa, United States
Illinois CancerCare - Bloomington
🇺🇸Bloomington, Illinois, United States
Graham Hospital
🇺🇸Canton, Illinois, United States
Illinois CancerCare - Carthage
🇺🇸Carthage, Illinois, United States
Memorial Hospital
🇺🇸Carthage, Illinois, United States
Illinois CancerCare - Eureka
🇺🇸Eureka, Illinois, United States
Mason District Hospital
🇺🇸Havana, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸Peoria, Illinois, United States
Illinois CancerCare - Princeton
🇺🇸Princeton, Illinois, United States
Elkhart Clinic, LLC
🇺🇸Elkhart, Indiana, United States
Memorial Hospital of South Bend
🇺🇸South Bend, Indiana, United States
McFarland Clinic, PC
🇺🇸Ames, Iowa, United States
Medical Oncology and Hematology Associates - West Des Moines
🇺🇸Clive, Iowa, United States
John Stoddard Cancer Center at Iowa Methodist Medical Center
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at John Stoddard Cancer Center
🇺🇸Des Moines, Iowa, United States
Medical Oncology and Hematology Associates at Mercy Cancer Center
🇺🇸Des Moines, Iowa, United States
John Stoddard Cancer Center at Iowa Lutheran Hospital
🇺🇸Des Moines, Iowa, United States
Siouxland Hematology-Oncology Associates, LLP
🇺🇸Sioux City, Iowa, United States
Mercy Cancer Center at Mercy Medical Center - North Iowa
🇺🇸Mason City, Iowa, United States
Mercy Medical Center - Sioux City
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas, PA - Chanute
🇺🇸Chanute, Kansas, United States
St. Luke's Regional Medical Center
🇺🇸Sioux City, Iowa, United States
Cancer Center of Kansas, PA - El Dorado
🇺🇸El Dorado, Kansas, United States
Cancer Center of Kansas-Independence
🇺🇸Independence, Kansas, United States
Cancer Center of Kansas, PA - Kingman
🇺🇸Kingman, Kansas, United States
Lawrence Memorial Hospital
🇺🇸Lawrence, Kansas, United States
Cancer Center of Kansas, PA - Liberal
🇺🇸Liberal, Kansas, United States
Cancer Center of Kansas, PA - Newton
🇺🇸Newton, Kansas, United States
Cancer Center of Kansas, PA - Parsons
🇺🇸Parsons, Kansas, United States
Cancer Center of Kansas, PA - Pratt
🇺🇸Pratt, Kansas, United States
Cancer Center of Kansas, PA - Salina
🇺🇸Salina, Kansas, United States
Cancer Center of Kansas, PA - Wellington
🇺🇸Wellington, Kansas, United States
Associates in Womens Health, PA - North Review
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Medical Arts Tower
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Wichita
🇺🇸Wichita, Kansas, United States
CCOP - Wichita
🇺🇸Wichita, Kansas, United States
Cancer Center of Kansas, PA - Winfield
🇺🇸Winfield, Kansas, United States
Via Christi Cancer Center at Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Battle Creek Health System Cancer Care Center
🇺🇸Battle Creek, Michigan, United States
Mecosta County Medical Center
🇺🇸Big Rapids, Michigan, United States
Green Bay Oncology, Limited - Escanaba
🇺🇸Escanaba, Michigan, United States
Butterworth Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
CCOP - Grand Rapids
🇺🇸Grand Rapids, Michigan, United States
Lacks Cancer Center at Saint Mary's Health Care
🇺🇸Grand Rapids, Michigan, United States
Dickinson County Healthcare System
🇺🇸Iron Mountain, Michigan, United States
Mercy General Health Partners
🇺🇸Muskegon, Michigan, United States
Michiana Hematology Oncology PC - Niles
🇺🇸Niles, Michigan, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸Saint Joseph, Michigan, United States
Lakeside Cancer Specialists, PLLC
🇺🇸Saint Joseph, Michigan, United States
Munson Medical Center
🇺🇸Traverse City, Michigan, United States
Metro Health Hospital
🇺🇸Wyoming, Michigan, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
CCOP - Metro-Minnesota
🇺🇸Saint Louis Park, Minnesota, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Ridgeview Medical Center
🇺🇸Waconia, Minnesota, United States
Lakeview Hospital
🇺🇸Stillwater, Minnesota, United States
United Hospital
🇺🇸Saint Paul, Minnesota, United States
Willmar Cancer Center at Rice Memorial Hospital
🇺🇸Willmar, Minnesota, United States
Minnesota Oncology Hematology, PA - Woodbury
🇺🇸Woodbury, Minnesota, United States
Hematology-Oncology Centers of the Northern Rockies - Billings
🇺🇸Billings, Montana, United States
Sletten Cancer Institute at Benefis Healthcare
🇺🇸Great Falls, Montana, United States
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
🇺🇸Missoula, Montana, United States
Green Bay Oncology, Limited - Oconto Falls
🇺🇸Oconto Falls, Wisconsin, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
St. Nicholas Hospital
🇺🇸Sheboygan, Wisconsin, United States
Medcenter One Hospital Cancer Care Center
🇺🇸Bismarck, North Dakota, United States
Michiana Hematology-Oncology, PC - Elkhart
🇺🇸Elkhart, Indiana, United States
Duluth Clinic Cancer Center - Duluth
🇺🇸Duluth, Minnesota, United States
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States