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Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)


OBJECTIVES:

Primary

- 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)

Secondary

- 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.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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

PRIOR CONCURRENT THERAPY:

- 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of temsirolimus (Phase I)

Safety Issue:

Yes

Principal Investigator

David J. Inwards, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Mayo Clinic

Authority:

United States: Federal Government

Study ID:

CDR0000619329

NCT ID:

NCT00787969

Start Date:

April 2009

Completion Date:

Related Keywords:

  • Lymphoma
  • 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
  • Lymphoma
  • Lymphoma, Mantle-Cell

Name

Location

Mayo Clinic ScottsdaleScottsdale, Arizona  85259
Mayo Clinic Cancer CenterRochester, Minnesota  55905
CCOP - WichitaWichita, Kansas  67214-3882
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
CCOP - Iowa Oncology Research AssociationDes Moines, Iowa  50309-1016
CCOP - Metro-MinnesotaSaint Louis Park, Minnesota  55416
Cedar Rapids Oncology AssociatesCedar Rapids, Iowa  52403
Mercy Medical Center - Sioux CitySioux City, Iowa  51104
Siouxland Hematology-Oncology Associates, LLPSioux City, Iowa  51101
St. Luke's Regional Medical CenterSioux City, Iowa  51104
Fairview Ridges HospitalBurnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy HospitalCoon Rapids, Minnesota  55433
Duluth Clinic Cancer Center - DuluthDuluth, Minnesota  55805-1983
CCOP - DuluthDuluth, Minnesota  55805
Miller - Dwan Medical CenterDuluth, Minnesota  55805
Fairview Southdale HospitalEdina, Minnesota  55435
Mercy and Unity Cancer Center at Unity HospitalFridley, Minnesota  55432
Hutchinson Area Health CareHutchinson, Minnesota  55350
Minnesota Oncology Hematology, PA - MaplewoodMaplewood, Minnesota  55109
HealthEast Cancer Care at St. John's HospitalMaplewood, Minnesota  55109
Hennepin County Medical Center - MinneapolisMinneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern HospitalMinneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical CenterShakopee, Minnesota  55379
Park Nicollet Cancer CenterSt. Louis Park, Minnesota  55416
Regions Hospital Cancer Care CenterSt. Paul, Minnesota  55101
United HospitalSt. Paul, Minnesota  55102
Ridgeview Medical CenterWaconia, Minnesota  55387
Minnesota Oncology Hematology, PA - WoodburyWoodbury, Minnesota  55125
Rapid City Regional HospitalRapid City, South Dakota  57709
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Montana Cancer ConsortiumBillings, Montana  59101
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Saint Joseph Regional Medical CenterSouth Bend, Indiana  46617
CCOP - Grand RapidsGrand Rapids, Michigan  49503
John Stoddard Cancer Center at Iowa Methodist Medical CenterDes Moines, Iowa  50309
Via Christi Cancer Center at Via Christi Regional Medical CenterWichita, Kansas  67214
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
Green Bay Oncology, Limited - EscanabaEscanaba, Michigan  49431
Dickinson County Healthcare SystemIron Mountain, Michigan  49801
St. Mary's Hospital Medical Center - Green BayGreen Bay, Wisconsin  54303
Green Bay Oncology, Limited at St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54301-3526
Green Bay Oncology, Limited at St. Mary's HospitalGreen Bay, Wisconsin  54303
Bay Area Cancer Care Center at Bay Area Medical CenterMarinette, Wisconsin  54143
Green Bay Oncology, Limited - Oconto FallsOconto Falls, Wisconsin  54154
Green Bay Oncology, Limited - Sturgeon BaySturgeon Bay, Wisconsin  54235
Battle Creek Health System Cancer Care CenterBattle Creek, Michigan  49017
Munson Medical CenterTraverse City, Michigan  49684
Hematology-Oncology Centers of the Northern Rockies - BillingsBillings, Montana  59101
St. Peter's HospitalHelena, Montana  59601
Kalispell Regional Medical CenterKalispell, Montana  59901
Glacier Oncology, PLLCKalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences CenterMissoula, Montana  59802
Butterworth Hospital at Spectrum HealthGrand Rapids, Michigan  49503-2560
Elkhart General HospitalElkhart, Indiana  46515
Howard Community HospitalKokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
St. Joseph Medical CenterBloomington, Illinois  61701
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
OSF St. Francis Medical CenterPeoria, Illinois  61637
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
Center for Cancer Therapy at LaPorte Hospital and Health ServicesLa Porte, Indiana  46350
Mercy Regional Cancer Center at Mercy Medical CenterCedar Rapids, Iowa  52403
John Stoddard Cancer Center at Iowa Lutheran HospitalDes Moines, Iowa  50316-2301
Medical Oncology and Hematology Associates at John Stoddard Cancer CenterDes Moines, Iowa  50309
Medical Oncology and Hematology Associates at Mercy Cancer CenterDes Moines, Iowa  50314
Mercy Cancer Center at Mercy Medical Center - Des MoinesDes Moines, Iowa  50314
Medical Oncology and Hematology Associates - West Des MoinesWest Des Moines, Iowa  50266
Cancer Center of Kansas, PA - Dodge CityDodge City, Kansas  67801
Mecosta County Medical CenterBig Rapids, Michigan  49307
Bismarck Cancer CenterBismarck, North Dakota  58501
Holy Family Memorial Medical Center Cancer Care CenterManitowoc, Wisconsin  54221-1450
Welch Cancer Center at Sheridan Memorial HospitalSheridan, Wyoming  82801
Mercy Cancer Center at Mercy Medical Center - North IowaMason City, Iowa  50401
Michiana Hematology-Oncology, PC - ElkhartElkhart, Indiana  46514
Elkhart Clinic, LLCElkhart, Indiana  46514-2098
Michiana Hematology Oncology PC - La PorteLa Porte, Indiana  46350
Michiana Hematology-Oncology, PC - South BendMishawaka, Indiana  46545-1470
Michiana Hematology Oncology PC - PlymouthPlymouth, Indiana  46563
McFarland Clinic, PCAmes, Iowa  50010
Cancer Center of Kansas, PA - ChanuteChanute, Kansas  66720
Cancer Center of Kansas, PA - El DoradoEl Dorado, Kansas  67042
Cancer Center of Kansas - Fort ScottFort Scott, Kansas  66701
Cancer Center of Kansas-IndependenceIndependence, Kansas  67301
Cancer Center of Kansas, PA - KingmanKingman, Kansas  67068
Lawrence Memorial HospitalLawrence, Kansas  66044
Cancer Center of Kansas, PA - LiberalLiberal, Kansas  67905
Cancer Center of Kansas, PA - NewtonNewton, Kansas  67114
Cancer Center of Kansas, PA - ParsonsParsons, Kansas  67357
Cancer Center of Kansas, PA - PrattPratt, Kansas  67124
Cancer Center of Kansas, PA - SalinaSalina, Kansas  67401
Cancer Center of Kansas, PA - WellingtonWellington, Kansas  67152
Cancer Center of Kansas, PA - WichitaWichita, Kansas  67214
Associates in Womens Health, PA - North ReviewWichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts TowerWichita, Kansas  67208
Cancer Center of Kansas, PA - WinfieldWinfield, Kansas  67156
Michiana Hematology Oncology PC - NilesNiles, Michigan  49120
Lakeside Cancer Specialists, PLLCSaint Joseph, Michigan  49085
Willmar Cancer Center at Rice Memorial HospitalWillmar, Minnesota  56201
Billings Clinic - DowntownBillings, Montana  59107-7000
Bozeman Deaconess Cancer CenterBozeman, Montana  59715
St. James Healthcare Cancer CareButte, Montana  59701
Great Falls Clinic - Main FacilityGreat Falls, Montana  59405
Sletten Cancer Institute at Benefis HealthcareGreat Falls, Montana  59405
Northern Montana HospitalHavre, Montana  59501
Kalispell Medical Oncology at KRMCKalispell, Montana  59901
Mid Dakota Clinic, PCBismarck, North Dakota  58501
Lacks Cancer Center at Saint Mary's Health CareGrand Rapids, Michigan  49503
Metro Health HospitalGrand Rapids, Michigan  49506
Galesburg Clinic, PCGalesburg, Illinois  61401
St. Vincent Healthcare Cancer Care ServicesBillings, Montana  59101
Illinois CancerCare - BloomingtonBloomington%, Illinois  61701
Illinois CancerCare - CantonCanton, Illinois  61520
Illinois CancerCare - CarthageCarthage, Illinois  62321
Illinois CancerCare - EurekaEureka, Illinois  61530
Illinois CancerCare - GalesburgGalesburg, Illinois  61401
Illinois CancerCare - HavanaHavana, Illinois  62644
Illinois CancerCare - Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare - MacombMacomb, Illinois  61455
OSF Holy Family Medical CenterMonmouth, Illinois  61462
Illinois CancerCare - MonmouthMonmouth, Illinois  61462
Illinois CancerCare - Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare - PekinPekin, Illinois  61603
Illinois CancerCare - PeruPeru, Illinois  61354
Illinois CancerCare - PrincetonPrinceton, Illinois  61356
Illinois CancerCare - Spring ValleySpring Valley, Illinois  61362
Mercy General Health PartnersMuskegon, Michigan  49443
Medcenter One Hospital Cancer Care CenterBismarck, North Dakota  58501
St. Alexius Medical Center Cancer CenterBismarck, North Dakota  58502
Humphrey Cancer Center at North Memorial Outpatient CenterRobbinsdale, Minnesota  55422-2900
Lakeview HospitalStillwater, Minnesota  55082
St. Nicholas HospitalSheboygan, Wisconsin  53081