Know Cancer

or
forgot password

A Phase II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)


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

Thank you

Trial Information

A Phase II Study of the Novel Proteasome Inhibitor Bortezomib in Combination With Rituximab, Cyclophosphamide and Prednisone in Patients With Relapsed/Refractory Indolent B-Cell Lymphoproliferative Disorders and Mantle Cell Lymphoma (MCL)


OBJECTIVES:

Primary

- Determine the maximum tolerated dose of bortezomib when given in combination with
rituximab, cyclophosphamide, and prednisone (R-CP) in patients with relapsed or
refractory indolent B-cell lymphoproliferative disorders or mantle cell lymphoma.
(phase I)

- Determine the frequency and duration of complete and partial responses in patients
treated with two different treatment regimes. (phase II)

Secondary

- Evaluate the progression-free survival, event-free survival, and overall survival of
patients treated with this regimen. (phase II)

- Evaluate the toxicity profile of this regimen.

OUTLINE: This is a phase I dose-escalation study of bortezomib followed by a phase II
randomized, multicenter study. Patients in phase II are stratified according to disease
(mantle cell lymphoma vs indolent B-cell lymphoproliferative disorder vs transformed
lymphoma).

- Phase I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral
prednisone on days 2-6, and bortezomib IV on days 2 and 7. Treatment repeats every 21
days for 8 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 1 of 3 or 2
of 6 patients experience dose-limiting toxicity.

- Phase II: Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral
prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on
days 2, 5, 9, and 12. Treatment repeats every 21 days for up to 8 courses in the
absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive cyclophosphamide IV and rituximab IV on day 1, oral
prednisone on days 2-6, and bortezomib IV (at the MTD determined in phase I) on
days 2 and 8. Treatment repeats every 21 days for up to 8 courses in the absence
of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 1 month, every 4 months for 2
years, and then every 6 months thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed diagnosis of 1 of the following:

- Chronic lymphocytic leukemia (CLL)

- B-cell small lymphocytic leukemia (SLL)

- Any marginal zone lymphoma

- Grade 1-3A follicular lymphoma

- Waldenstrom's macroglobulinemia

- Mantle cell lymphoma

- No transformed indolent lymphoma

- Assessable disease (phase I)

- Measurable disease (phase I and II), defined as ≥ one lesion that can be accurately
measured in ≥ 1 dimension as ≥ 2 cm by conventional techniques OR ≥ 1 cm by spiral CT
scan

- Lymph nodes measuring ≤ 1 cm in the short axis are considered normal

- Relapsed or refractory disease

- Must have received at least 1 prior therapeutic regimen but no more than 3 prior
conventional cytotoxic therapy regimens

- No known brain metastases or meningeal disease

PATIENT CHARACTERISTICS:

- Karnofsky performance status > 50%

- Absolute neutrophil count > 1,000/mcl (more than 500/mcl if known lymphomatous
involvement)

- Platelet count ≥ 50,000/mcl

- Total bilirubin < 1.5 times upper limit of normal (ULN) (less than 5 mg/dL if known
history of Gilbert's disease)

- AST and ALT ≤ 2.5 times ULN (4 times ULN if liver involvement)

- Creatinine < 1.5 times ULN OR creatinine clearance > 50 mL/min

- Patients may have febrile episodes up to 38.5ºC without evidence of active infection

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No New York Heart Association class III or IV congestive heart failure

- No uncontrolled intercurrent illness, including any of the following:

- Ongoing or active infection

- Cerebrovascular accident or transient ischemic attack within 6 months of study
entry

- Unstable angina pectoris

- Cardiac arrhythmia

- EKG evidence of acute ischemia

- Psychiatric illness/social situations that would limit compliance with study
requirements

- No uncontrolled hypertension requiring active manipulation of antihypertensive
medications

- No known or active HIV infection

- No history of hypersensitivity to bortezomib, boron, or mannitol

- No peripheral neuropathy > grade 2

- No other malignancy within the past 5 years except curatively treated non
life-threatening malignancies, such as cutaneous basal cell or squamous cell
carcinoma or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Recovered from prior therapy

- Prior stem cell transplantation allowed

- Preparative cytoreductive and high-dose therapies considered 1 prior therapy

- At least 4 weeks since prior cytotoxic chemotherapy (6 weeks since prior nitrosoureas
or mitomycin C)

- At least 12 weeks since prior radioimmunotherapy

- One prior course comprising tositumomab or ibritumomab tiuxetan allowed

- At least 1 week since prior palliative steroids for NHL

- No therapeutic monoclonal antibodies (e.g., rituximab, tositumomab, ibritumomab,
alemtuzumab, etc.) within 3 months of study entry

- Patients treated with monoclonal antibodies within 3 months allowed provided
disease progressed on this therapy AND no treatment received 7 days prior to
study entry

- Seven days since prior rituximab (for patients enrolled in phase I portion)

- No major surgery within 4 weeks of study entry

- No other concurrent investigational agents

- No other concurrent anticancer therapy

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

John F. Gerecitano, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

05-103

NCT ID:

NCT00295932

Start Date:

December 2005

Completion Date:

September 2014

Related Keywords:

  • Leukemia
  • Lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent small lymphocytic lymphoma
  • recurrent marginal zone lymphoma
  • Waldenstrom macroglobulinemia
  • recurrent mantle cell lymphoma
  • refractory chronic lymphocytic leukemia
  • B-cell chronic lymphocytic leukemia
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoproliferative Disorders
  • Lymphoma, Mantle-Cell

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Herbert Irving Comprehensive Cancer Center at Columbia University Medical CenterNew York, New York  10032
Memorial Sloan-Kettering at Basking RidgeBasking Ridge, New Jersey  07920
Memorial Sloan-Kettering Cancer Center @ SuffolkCommack, New York  11725
Memorial Sloan-Kettering at Mercy Medical CenterRockville Centre, New York  
Memoral Sloan Kettering Cancer Center@PhelpsSleepy Hollow, New York