Clinical trial NCT00244985: Rituximab and Liposomal Doxorubicin in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase I/II Pilot Study of the Safety and Efficacy of Rituxan (Chimeric Anti-CD20 Antibody) in Combination With Doxil (Liposomal Doxorubicin) Chemotherapy in Patients With Relapsing or Refractory Indolent or Aggressive B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent small lymphocytic lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Ortho Biotech, Inc.
First posted: 2005-10-27
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: 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. Drugs used in chemotherapy, such as liposomal doxorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with liposomal doxorubicin may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects of giving rituximab together with liposomal doxorubicin and to see how well they work in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

Primary

* Determine the safety, including qualitative and quantitative toxic effects and their duration and reversibility, of rituximab and doxorubicin HCl liposome in patients with relapsed or refractory, indolent or aggressive CD20-positive B-cell non-Hodgkin's lymphoma.

Secondary

* Determine the efficacy, including overall response rate and durability of objective response, of this regimen in these patients.
* Correlate pretreatment functional, phenotypic, and genotypic characteristics of host immune effector cells with response in patients treated with this regimen.

OUTLINE: This is an open-label, pilot study.

Patients receive rituximab IV over 3-8 hours on day 1 and doxorubicin HCl liposome IV over 1-3 hours on day 3. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 4 years.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following indolent or aggressive B-cell non-Hodgkin's lymphoma (NHL) subtypes:

  * Grade 1-3 follicular lymphoma
  * Mantle cell lymphoma
  * Small lymphocytic lymphoma
  * Diffuse large B-cell lymphoma
  * Diffuse mixed cell lymphoma
  * Marginal zone lymphoma
* Relapsed or refractory CD20-positive disease
* Measurable disease
* Must have received ≥ 1 but \< 4 prior standard chemotherapy regimens
* No Burkitt's lymphoma or precursor B-lymphoblastic lymphoma
* No CNS lymphoma

PATIENT CHARACTERISTICS:

Performance status

* Karnofsky 60-100%

Life expectancy

* At least 6 months

Hematopoietic

* Absolute neutrophil count ≥ 1,500/mm\^3
* Platelet count ≥ 75,000/mm\^3
* Hemoglobin \> 7 g/dL

Hepatic

* AST or ALT \< 2 times upper limit of normal (unless due to primary disease)
* Bilirubin ≤ 2 mg/dL

Renal

* Creatinine ≤ 2.0 mg/dL

Cardiovascular

* LVEF ≥ 50% by MUGA and/or 2-D echocardiogram
* No history of New York Heart Association class II-IV cardiac disease
* No congestive heart failure

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No known HIV positivity
* No uncontrolled active bacterial, viral, or fungal infection
* No other serious disease that would preclude study participation
* No other primary malignancy within the past 5 years except squamous cell or basal cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Recovered from prior immunotherapy
* Prior immunotherapy, including rituximab or other monoclonal antibody, allowed

Chemotherapy

* See Disease Characteristics
* More than 4 weeks since prior chemotherapy and recovered
* No prior doxorubicin (or equivalent anthracycline) at a cumulative dose \> 400 mg/m\^2
* No other concurrent chemotherapy

Endocrine therapy

* Nonsteroidal hormones for nonlymphoma-related conditions (e.g., insulin for diabetes) allowed
* No concurrent corticosteroids except for a transient inflammatory reaction (i.e., skin rash or hives)

Radiotherapy

* Recovered from prior radiotherapy
* No concurrent radiotherapy

Surgery

* More than 4 weeks since prior major surgery (other than diagnostic surgery) and recovered

Other

* No other concurrent antitumor agents
* No other concurrent investigational agents

Primary outcomes:
measure: Complete Response Rate at 20 Weeks
timeFrame: 20 weeks
Secondary outcomes:
measure: Partial Response Rate at 20 Weeks
timeFrame: 20 weeks
measure: Overall Response Rate (Complete and Partial Responses) at 20 Weeks
timeFrame: 20 weeks
measure: Progression Free Survival (PFS) Rate at 2 Years
timeFrame: 2 years
measure: Overall Survival (OS) Rate at 2 Years
timeFrame: 2 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Myron S. Czuczman, MD
role: PRINCIPAL_INVESTIGATOR
References: