Clinical trial NCT00109967: CCI-779 and Rituximab in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase II Study of CCI-779 in Combination With Rituximab in Patients With Relapsed or Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Mantle Cell Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2005-05-04
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall Response Rate (Complete and Partial Responses) as Defined by the International Workshop Criteria
timeFrame: Up to 12, 28-day cycles.
Secondary outcomes:
measure: Time to Progression
timeFrame: Patients were followed up to five years after registration.
measure: Duration of Response
timeFrame: Response duration is followed up to 5 years from registration.
measure: Toxicity
timeFrame: Assessed during treatment (up to 12, 28-day cycles)
measure: Overall Survival
timeFrame: Patients were followed for survival status for up to 5 years.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Aurora
country: United States
facility: The Medical Center of Aurora
state: Colorado
city: Boulder
country: United States
facility: Boulder Community Hospital
state: Colorado
city: Colorado Springs
country: United States
facility: Penrose-Saint Francis Healthcare
state: Colorado
city: Denver
country: United States
facility: Saint Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Exempla Saint Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - Saint Lukes Medical Center - Health One
state: Colorado
city: Denver
country: United States
facility: Rose Medical Center
state: Colorado
city: Denver
country: United States
facility: Colorado Cancer Research Program CCOP
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Grand Junction
country: United States
facility: Saint Mary's Hospital and Regional Medical Center
state: Colorado
city: Greeley
country: United States
facility: North Colorado Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Longmont
country: United States
facility: Longmont United Hospital
state: Colorado
city: Loveland
country: United States
facility: McKee Medical Center
state: Colorado
city: Pueblo
country: United States
facility: Saint Mary Corwin Medical Center
state: Colorado
city: Thornton
country: United States
facility: North Suburban Medical Center
state: Colorado
city: Wheat Ridge
country: United States
facility: Exempla Lutheran Medical Center
state: Colorado
city: Aurora
country: United States
facility: Rush - Copley Medical Center
state: Illinois
city: Bloomington
country: United States
facility: Saint Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital Association
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Eureka
country: United States
facility: Eureka Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex - Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: Mcdonough District Hospital
state: Illinois
city: Normal
country: United States
facility: Bromenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center Foundation
state: Illinois
city: Ottawa
country: United States
facility: Illinois CancerCare-Ottawa Clinic
state: Illinois
city: Ottawa
country: United States
facility: Ottawa Regional Hospital and Healthcare Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Cancer Treatment Center
state: Illinois
city: Pekin
country: United States
facility: Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Peoria
country: United States
facility: Illinois Oncology Research Association CCOP
state: Illinois
city: Peoria
country: United States
facility: OSF Saint Francis Medical Center
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: Saint Margaret's Hospital
state: Illinois
city: Urbana
country: United States
facility: Carle Clinic-Urbana Main
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation dba Carle Cancer Center
state: Illinois
city: Beech Grove
country: United States
facility: Saint Francis Hospital and Health Centers
state: Indiana
city: Michigan City
country: United States
facility: Saint Anthony Memorial Health Center
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital and Health Care Services
state: Indiana
city: Ames
country: United States
facility: McFarland Clinic
state: Iowa
city: Cedar Rapids
country: United States
facility: Saint Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Cedar Rapids Oncology Association
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Oncology Associates
state: Iowa
city: Clive
country: United States
facility: Medical Oncology and Hematology Associates-West Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Mercy Capitol
state: Iowa
city: Des Moines
country: United States
facility: Iowa Methodist Medical Center
state: Iowa
city: Des Moines
country: United States
facility: Iowa Oncology Research Association CCOP
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates-Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Medical Oncology and Hematology Associates
state: Iowa
city: Des Moines
country: United States
facility: Mercy Medical Center - Des Moines
state: Iowa
city: Des Moines
country: United States
facility: Iowa Lutheran Hospital
state: Iowa
city: Mason City
country: United States
facility: Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Regional Cancer Center
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology - Oncology Associates
state: Iowa
city: Sioux City
country: United States
facility: Mercy Medical Center-Sioux City
state: Iowa
city: Sioux City
country: United States
facility: Saint Luke's Regional Medical Center
state: Iowa
city: Anthony
country: United States
facility: Hospital District Sixth of Harper County
state: Kansas
city: Chanute
country: United States
facility: Cancer Center of Kansas - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas-Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas - Newton
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas - Salina
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates In Womens Health
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas-Wichita Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas - Main Office
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wichita CCOP
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas - Winfield
state: Kansas
city: Adrian
country: United States
facility: Bixby Medical Center
state: Michigan
city: Adrian
country: United States
facility: Hickman Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Hospital
state: Michigan
city: Ann Arbor
country: United States
facility: Michigan Cancer Research Consortium Community Clinical Oncology Program
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Hospital
state: Michigan
city: Detroit
country: United States
facility: Saint John Hospital and Medical Center
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Flint
country: United States
facility: Genesys Regional Medical Center
state: Michigan
city: Jackson
country: United States
facility: Allegiance Health
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Livonia
country: United States
facility: Saint Mary Mercy Hospital
state: Michigan
city: Monroe
country: United States
facility: Community Cancer Center of Monroe
state: Michigan
city: Monroe
country: United States
facility: Mercy Memorial Hospital
state: Michigan
city: Pontiac
country: United States
facility: Saint Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Saint Joseph Mercy Port Huron
state: Michigan
city: Saginaw
country: United States
facility: Saint Mary's of Michigan
state: Michigan
city: Warren
country: United States
facility: Saint John Macomb-Oakland Hospital
state: Michigan
city: Bemidji
country: United States
facility: Merit Care Clinic Bemidji
state: Minnesota
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: Duluth Clinic CCOP
state: Minnesota
city: Duluth
country: United States
facility: Miller-Dwan Hospital
state: Minnesota
city: Duluth
country: United States
facility: Saint Mary's Medical Center
state: Minnesota
city: Edina
country: United States
facility: Fairview-Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Unity Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology Hematology PA-Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Abbott-Northwestern Hospital
state: Minnesota
city: Robbinsdale
country: United States
facility: North Memorial Medical Health Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro-Minnesota CCOP
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Saint Louis Park
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: Saint Francis Regional Medical Center
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology and Hematology PA-Woodbury
state: Minnesota
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies PC
state: Montana
city: Billings
country: United States
facility: Montana Cancer Consortium CCOP
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: Saint Vincent Healthcare
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Billings
country: United States
facility: Deaconess Medical Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Hospital
state: Montana
city: Butte
country: United States
facility: Saint James Community Hospital and Cancer Treatment Center
state: Montana
city: Great Falls
country: United States
facility: Berdeaux, Donald MD (UIA Investigator)
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: Saint Peter's Community Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Hospital
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists
state: Montana
city: Missoula
country: United States
facility: Saint Patrick Hospital - Community Hospital
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Rutherfordton
country: United States
facility: Rutherford Hospital
state: North Carolina
city: Bismarck
country: United States
facility: Bismarck Cancer Center
state: North Dakota
city: Bismarck
country: United States
facility: Medcenter One Health Systems
state: North Dakota
city: Bismarck
country: United States
facility: Mid Dakota Clinic
state: North Dakota
city: Bismarck
country: United States
facility: Saint Alexius Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Meritcare Hospital
state: North Dakota
city: Fargo
country: United States
facility: MeritCare Medical Group
state: North Dakota
city: Bowling Green
country: United States
facility: Wood County Oncology Center
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital - Dayton
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Health Center
state: Ohio
city: Dayton
country: United States
facility: Veteran Affairs Medical Center
state: Ohio
city: Dayton
country: United States
facility: Dayton CCOP
state: Ohio
city: Elyria
country: United States
facility: Hematology Oncology Center Incorporated
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Hospital
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Fremont
country: United States
facility: Fremont Memorial Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kenton
country: United States
facility: Cole, Sharon, K. M.D. (UIA Investigator)
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Lima
country: United States
facility: Lima Memorial Hospital
state: Ohio
city: Maumee
country: United States
facility: Northwest Ohio Oncology Center
state: Ohio
city: Maumee
country: United States
facility: Saint Luke's Hospital
state: Ohio
city: Maumee
country: United States
facility: Toledo Radiation Oncology at Northwest Ohio Onocolgy Center
state: Ohio
city: Oregon
country: United States
facility: Bayview Oncology Associates
state: Ohio
city: Oregon
country: United States
facility: Saint Charles Hospital
state: Ohio
city: Sandusky
country: United States
facility: Firelands Regional Medical Center
state: Ohio
city: Sandusky
country: United States
facility: North Coast Cancer Care
state: Ohio
city: Sylvania
country: United States
facility: Flower Memorial Hospital
state: Ohio
city: Tiffin
country: United States
facility: Mercy Hospital of Tiffin
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Toledo
country: United States
facility: Saint Vincent Mercy Medical Center
state: Ohio
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Toledo
country: United States
facility: Toledo Community Hospital Oncology Program CCOP
state: Ohio
city: Toledo
country: United States
facility: Mercy Cancer Center at Saint Anne Mercy Hospital
state: Ohio
city: Toledo
country: United States
facility: Stark, Michael, Edward. M.D. (UIA Investigator)
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: Wauseon
country: United States
facility: Fulton County Health Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Greene Memorial Hospital
state: Ohio
city: Allentown
country: United States
facility: Lehigh Valley Hospital
state: Pennsylvania
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: State College
country: United States
facility: Geisinger Medical Group
state: Pennsylvania
city: Wilkes-Barre
country: United States
facility: Geisinger Wyoming Valley
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health Hospital
state: South Carolina
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Upstate Carolina CCOP
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Sioux Falls
country: United States
facility: Avera McKennan Hospital and University Health Center
state: South Dakota
city: Fredericksburg
country: United States
facility: Fredericksburg Oncology Inc
state: Virginia
city: Sheridan
country: United States
facility: Welch Cancer Center
state: Wyoming
Study officials:
affiliation: North Central Cancer Treatment Group
name: Stephen Ansell
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ansell SM, Tang H, Kurtin PJ, Koenig PA, Inwards DJ, Shah K, Ziesmer SC, Feldman AL, Rao R, Gupta M, Erlichman C, Witzig TE. Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study. Lancet Oncol. 2011 Apr;12(4):361-8. doi: 10.1016/S1470-2045(11)70062-6.