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

Phase 2

Completed

Conditions: Recurrent Mantle Cell Lymphoma

Interventions: Biological: rituximab
Drug: temsirolimus

Registration Number: NCT00109967

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This phase II trial is studying how well giving CCI-779 together with rituximab works in treating patients with relapsed or refractory mantle cell lymphoma. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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. Giving CCI-779 together with rituximab may kill more cancer cells

Detailed Description: PRIMARY OBJECTIVES:

I. Determine the overall response rate in patients with relapsed or refractory mantle cell lymphoma treated with CCI-779 and rituximab.

II. Determine the tolerability of this regimen in these patients by assessing toxicity.

SECONDARY OBJECTIVES:

I. Determine the time to disease progression and overall survival of patients treated with this regimen.

II. Determine the duration of response in patients treated with this regimen.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

Inclusion Criteria

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
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 central nervous system involvement (e.g., parenchymal mass or leptomeningeal involvement)
Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
At least 3 months
No other concurrent treatment for MCL
Absolute neutrophil count ≥ 1,000/mm^3
Platelet count ≥ 75,000/mm^3
Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
Direct bilirubin < 1.5 times ULN
Aspartate aminotransferase (AST) ≤ 3 times ULN (5 times ULN if liver involvement by MCL is present)
Creatinine ≤ 2 times ULN
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
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
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
Prior chemotherapy allowed
No other concurrent chemotherapy
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
Prior radiotherapy allowed
No prior treatment with a mammalian target of rapamycin (mTOR) inhibitor
No other concurrent investigational or commercial agents or therapies for MCL
No other concurrent immunosuppressive therapy

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	rituximab	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.
Arm I	temsirolimus	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.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria	Up to 12, 28-day cycles.	Complete Response (CR) - Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms. Partial Response (PR) requires a \>=50% decrease in sum of the products of the greatest dimension (SPD) of the six largest dominant nodes or nodal masses. Overall Response Rate (ORR) - The number of patients who achieve a CR or PR divided by the total number of evaluable patients. We report the Overall Response Rate here.

Secondary Outcome Measures

Name	Time	Method
Time to Progression	Patients were followed up to five years after registration.	Time to progression was defined as the time from registration to the date of progression. Patients who died without disease progression were censored at the date of their last evaluation. Patients who were still receiving treatment at the time of these analyses were censored at the date of their last evaluation. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
Duration of Response	Response duration is followed up to 5 years from registration.	Duration of response was defined as the time from the date of documented response to the date of progression. Patients who went off treatment due to other reasons (eg, adverse reactions, refusal of further treatment) were censored at that time. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.
Toxicity	Assessed during treatment (up to 12, 28-day cycles)	As per the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) Version 3, toxicity was defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment by the treating physician. In this section, we report the number of participants that experienced at least one Grade 3 or higher adverse event.
Overall Survival	Patients were followed for survival status for up to 5 years.	Overall survival (OS) was defined as the time from registration to death resulting from any cause. The distribution of this time-to-event end point was estimated using the Kaplan-Meier method.

Trial Locations

Locations (193): Mobile Infirmary Medical Center
🇺🇸
Mobile, Alabama, United States
Saint Mary Corwin Medical Center
🇺🇸
Pueblo, Colorado, United States
Graham Hospital Association
🇺🇸
Canton, Illinois, United States
Mercy Hospital
🇺🇸
Coon Rapids, Minnesota, United States
Cancer Center of Kansas-Independence
🇺🇸
Independence, Kansas, United States
Fredericksburg Oncology Inc
🇺🇸
Fredericksburg, Virginia, United States
Hurley Medical Center
🇺🇸
Flint, Michigan, United States
Saint John Macomb-Oakland Hospital
🇺🇸
Warren, Michigan, United States
Kalispell Medical Oncology
🇺🇸
Kalispell, Montana, United States
Spartanburg Regional Medical Center
🇺🇸
Spartanburg, South Carolina, United States
Miller-Dwan Hospital
🇺🇸
Duluth, Minnesota, United States
Geisinger Wyoming Valley
🇺🇸
Wilkes-Barre, Pennsylvania, United States
Glacier Oncology PLLC
🇺🇸
Kalispell, Montana, United States
Swedish Medical Center
🇺🇸
Englewood, Colorado, United States
Saint James Community Hospital and Cancer Treatment Center
🇺🇸
Butte, Montana, United States
Hematology-Oncology Centers of the Northern Rockies PC
🇺🇸
Billings, Montana, United States
Bozeman Deaconess Hospital
🇺🇸
Bozeman, Montana, United States
Great Falls Clinic
🇺🇸
Great Falls, Montana, United States
Saint Peter's Community Hospital
🇺🇸
Helena, Montana, United States
Community Medical Hospital
🇺🇸
Missoula, Montana, United States
Montana Cancer Specialists
🇺🇸
Missoula, Montana, United States
Saint Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Carle Clinic-Urbana Main
🇺🇸
Urbana, Illinois, United States
North Suburban Medical Center
🇺🇸
Thornton, Colorado, United States
Community Cancer Center Foundation
🇺🇸
Normal, Illinois, United States
Saint Anthony Memorial Health Center
🇺🇸
Michigan City, Indiana, United States
Mercy Medical Center - North Iowa
🇺🇸
Mason City, Iowa, United States
Eureka Hospital
🇺🇸
Eureka, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Illinois Oncology Research Association CCOP
🇺🇸
Peoria, Illinois, United States
Boulder Community Hospital
🇺🇸
Boulder, Colorado, United States
Kewanee Hospital
🇺🇸
Kewanee, Illinois, United States
Bromenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Pekin Hospital
🇺🇸
Pekin, Illinois, United States
Wichita CCOP
🇺🇸
Wichita, Kansas, United States
Illinois CancerCare-Peoria
🇺🇸
Peoria, Illinois, United States
OSF Saint Francis Medical Center
🇺🇸
Peoria, Illinois, United States
Cancer Center of Kansas - Newton
🇺🇸
Newton, Kansas, United States
Cancer Center of Kansas - Pratt
🇺🇸
Pratt, Kansas, United States
Illinois CancerCare-Ottawa Clinic
🇺🇸
Ottawa, Illinois, United States
Medical Oncology and Hematology Associates-West Des Moines
🇺🇸
Clive, Iowa, United States
Allegiance Health
🇺🇸
Jackson, Michigan, United States
Cancer Center of Kansas-Kingman
🇺🇸
Kingman, Kansas, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Saint Luke's Hospital
🇺🇸
Maumee, Ohio, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
Community Cancer Center of Monroe
🇺🇸
Monroe, Michigan, United States
Fairview Ridges Hospital
🇺🇸
Burnsville, Minnesota, United States
Pekin Cancer Treatment Center
🇺🇸
Pekin, Illinois, United States
Cedar Rapids Oncology Association
🇺🇸
Cedar Rapids, Iowa, United States
Cancer Center of Kansas - Dodge City
🇺🇸
Dodge City, Kansas, United States
Oncology Associates
🇺🇸
Cedar Rapids, Iowa, United States
Lawrence Memorial Hospital
🇺🇸
Lawrence, Kansas, United States
Saint Joseph Mercy Port Huron
🇺🇸
Port Huron, Michigan, United States
Unity Hospital
🇺🇸
Fridley, Minnesota, United States
Duluth Clinic CCOP
🇺🇸
Duluth, Minnesota, United States
Saint Joseph Mercy Oakland
🇺🇸
Pontiac, Michigan, United States
Minnesota Oncology Hematology PA-Maplewood
🇺🇸
Maplewood, Minnesota, United States
Ridgeview Medical Center
🇺🇸
Waconia, Minnesota, United States
Cancer Center of Kansas - El Dorado
🇺🇸
El Dorado, Kansas, United States
Siouxland Hematology - Oncology Associates
🇺🇸
Sioux City, Iowa, United States
Mercy Medical Center-Sioux City
🇺🇸
Sioux City, Iowa, United States
Sparrow Hospital
🇺🇸
Lansing, Michigan, United States
Saint Mary's Medical Center
🇺🇸
Duluth, Minnesota, United States
Oakwood Hospital
🇺🇸
Dearborn, Michigan, United States
Cancer Center of Kansas - Fort Scott
🇺🇸
Fort Scott, Kansas, United States
Mercy Hospital of Tiffin
🇺🇸
Tiffin, Ohio, United States
Metro-Minnesota CCOP
🇺🇸
Saint Louis Park, Minnesota, United States
Geisinger Medical Center
🇺🇸
Danville, Pennsylvania, United States
Geisinger Medical Group
🇺🇸
State College, Pennsylvania, United States
Hickman Cancer Center
🇺🇸
Adrian, Michigan, United States
Merit Care Clinic Bemidji
🇺🇸
Bemidji, Minnesota, United States
Welch Cancer Center
🇺🇸
Sheridan, Wyoming, United States
Minnesota Oncology and Hematology PA-Woodbury
🇺🇸
Woodbury, Minnesota, United States
Medcenter One Health Systems
🇺🇸
Bismarck, North Dakota, United States
Samaritan North Health Center
🇺🇸
Dayton, Ohio, United States
Montana Cancer Consortium CCOP
🇺🇸
Billings, Montana, United States
Kalispell Regional Medical Center
🇺🇸
Kalispell, Montana, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Veteran Affairs Medical Center
🇺🇸
Dayton, Ohio, United States
Saint Francis Regional Medical Center
🇺🇸
Shakopee, Minnesota, United States
Northern Montana Hospital
🇺🇸
Havre, Montana, United States
Stark, Michael, Edward. M.D. (UIA Investigator)
🇺🇸
Toledo, Ohio, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
Billings Clinic
🇺🇸
Billings, Montana, United States
Bozeman Deaconess Cancer Center
🇺🇸
Bozeman, Montana, United States
Firelands Regional Medical Center
🇺🇸
Sandusky, Ohio, United States
Saint Charles Hospital
🇺🇸
Oregon, Ohio, United States
Saint Patrick Hospital - Community Hospital
🇺🇸
Missoula, Montana, United States
Bismarck Cancer Center
🇺🇸
Bismarck, North Dakota, United States
Clinton Memorial Hospital
🇺🇸
Wilmington, Ohio, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Lehigh Valley Hospital
🇺🇸
Allentown, Pennsylvania, United States
AnMed Health Hospital
🇺🇸
Anderson, South Carolina, United States
Upstate Carolina CCOP
🇺🇸
Spartanburg, South Carolina, United States
Avera Cancer Institute
🇺🇸
Sioux Falls, South Dakota, United States
Lima Memorial Hospital
🇺🇸
Lima, Ohio, United States
Greene Memorial Hospital
🇺🇸
Xenia, Ohio, United States
Abbott-Northwestern Hospital
🇺🇸
Minneapolis, Minnesota, United States
Saint John Hospital and Medical Center
🇺🇸
Detroit, Michigan, United States
Saint Anthony Central Hospital
🇺🇸
Denver, Colorado, United States
Porter Adventist Hospital
🇺🇸
Denver, Colorado, United States
Exempla Saint Joseph Hospital
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Rose Medical Center
🇺🇸
Denver, Colorado, United States
Colorado Cancer Research Program CCOP
🇺🇸
Denver, Colorado, United States
Cancer Center of Kansas - Salina
🇺🇸
Salina, Kansas, United States
Associates In Womens Health
🇺🇸
Wichita, Kansas, United States
North Colorado Medical Center
🇺🇸
Greeley, Colorado, United States
Sky Ridge Medical Center
🇺🇸
Lone Tree, Colorado, United States
Avera McKennan Hospital and University Health Center
🇺🇸
Sioux Falls, South Dakota, United States
Dayton CCOP
🇺🇸
Dayton, Ohio, United States
Cancer Center of Kansas-Wichita Medical Arts Tower
🇺🇸
Wichita, Kansas, United States
Saint Mary's of Michigan
🇺🇸
Saginaw, Michigan, United States
Genesys Regional Medical Center
🇺🇸
Flint, Michigan, United States
Mercy Memorial Hospital
🇺🇸
Monroe, Michigan, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
Saint Mary's Hospital and Regional Medical Center
🇺🇸
Grand Junction, Colorado, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Longmont United Hospital
🇺🇸
Longmont, Colorado, United States
Exempla Lutheran Medical Center
🇺🇸
Wheat Ridge, Colorado, United States
McKee Medical Center
🇺🇸
Loveland, Colorado, United States
Rush - Copley Medical Center
🇺🇸
Aurora, Illinois, United States
Galesburg Clinic
🇺🇸
Galesburg, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Joliet Oncology-Hematology Associates Limited
🇺🇸
Joliet, Illinois, United States
Hopedale Medical Complex - Hospital
🇺🇸
Hopedale, Illinois, United States
Mcdonough District Hospital
🇺🇸
Macomb, Illinois, United States
Ottawa Regional Hospital and Healthcare Center
🇺🇸
Ottawa, Illinois, United States
Illinois Valley Hospital
🇺🇸
Peru, Illinois, United States
Saint Margaret's Hospital
🇺🇸
Spring Valley, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
Carle Foundation dba Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Saint Francis Hospital and Health Centers
🇺🇸
Beech Grove, Indiana, United States
Reid Hospital and Health Care Services
🇺🇸
Richmond, Indiana, United States
McFarland Clinic
🇺🇸
Ames, Iowa, United States
Hospital District Sixth of Harper County
🇺🇸
Anthony, Kansas, United States
Siouxland Regional Cancer Center
🇺🇸
Sioux City, Iowa, United States
Cancer Center of Kansas - Chanute
🇺🇸
Chanute, Kansas, United States
Cancer Center of Kansas - Parsons
🇺🇸
Parsons, Kansas, United States
Cancer Center of Kansas - Wellington
🇺🇸
Wellington, Kansas, United States
Via Christi Regional Medical Center
🇺🇸
Wichita, Kansas, United States
Cancer Center of Kansas - Winfield
🇺🇸
Winfield, Kansas, United States
Cancer Center of Kansas - Main Office
🇺🇸
Wichita, Kansas, United States
Bixby Medical Center
🇺🇸
Adrian, Michigan, United States
Saint Mary Mercy Hospital
🇺🇸
Livonia, Michigan, United States
Fairview-Southdale Hospital
🇺🇸
Edina, Minnesota, United States
North Memorial Medical Health Center
🇺🇸
Robbinsdale, Minnesota, United States
Park Nicollet Clinic - Saint Louis Park
🇺🇸
Saint Louis Park, Minnesota, United States
United Hospital
🇺🇸
Saint Paul, Minnesota, United States
Northern Rockies Radiation Oncology Center
🇺🇸
Billings, Montana, United States
Deaconess Medical Center
🇺🇸
Billings, Montana, United States
Saint Vincent Healthcare
🇺🇸
Billings, Montana, United States
Berdeaux, Donald MD (UIA Investigator)
🇺🇸
Great Falls, Montana, United States
Guardian Oncology and Center for Wellness
🇺🇸
Missoula, Montana, United States
Rutherford Hospital
🇺🇸
Rutherfordton, North Carolina, United States
Saint Alexius Medical Center
🇺🇸
Bismarck, North Dakota, United States
Mid Dakota Clinic
🇺🇸
Bismarck, North Dakota, United States
Meritcare Hospital
🇺🇸
Fargo, North Dakota, United States
MeritCare Medical Group
🇺🇸
Fargo, North Dakota, United States
Wood County Oncology Center
🇺🇸
Bowling Green, Ohio, United States
Grandview Hospital
🇺🇸
Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Hematology Oncology Center Incorporated
🇺🇸
Elyria, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Fremont Memorial Hospital
🇺🇸
Fremont, Ohio, United States
Cole, Sharon, K. M.D. (UIA Investigator)
🇺🇸
Kenton, Ohio, United States
Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
🇺🇸
Maumee, Ohio, United States
Northwest Ohio Oncology Center
🇺🇸
Maumee, Ohio, United States
North Coast Cancer Care
🇺🇸
Sandusky, Ohio, United States
Bayview Oncology Associates
🇺🇸
Oregon, Ohio, United States
Flower Memorial Hospital
🇺🇸
Sylvania, Ohio, United States
The Toledo Hospital
🇺🇸
Toledo, Ohio, United States
Saint Vincent Mercy Medical Center
🇺🇸
Toledo, Ohio, United States
University of Toledo
🇺🇸
Toledo, Ohio, United States
Mercy Cancer Center at Saint Anne Mercy Hospital
🇺🇸
Toledo, Ohio, United States
Toledo Community Hospital Oncology Program CCOP
🇺🇸
Toledo, Ohio, United States
Toledo Clinic
🇺🇸
Toledo, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Fulton County Health Center
🇺🇸
Wauseon, Ohio, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Saint Joseph Mercy Hospital
🇺🇸
Ann Arbor, Michigan, United States
Michigan Cancer Research Consortium Community Clinical Oncology Program
🇺🇸
Ann Arbor, Michigan, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Mercy Capitol
🇺🇸
Des Moines, Iowa, United States
Iowa Methodist Medical Center
🇺🇸
Des Moines, Iowa, United States
Iowa Oncology Research Association CCOP
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates-Des Moines
🇺🇸
Des Moines, Iowa, United States
Medical Oncology and Hematology Associates
🇺🇸
Des Moines, Iowa, United States
Mercy Medical Center - Des Moines
🇺🇸
Des Moines, Iowa, United States
Iowa Lutheran Hospital
🇺🇸
Des Moines, Iowa, United States