Clinical trial NCT00058292: Radiolabeled Monoclonal Antibody Therapy and High-Dose Chemotherapy Followed By Autologous Peripheral Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase I Trial Combining IDEC-Y2B8 And High-Dose Beam Chemotherapy With Hematopoietic Progenitor Cell Transplant In Patients With Relapsed Or Refractory B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Keywords: recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent mantle cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-04-09
Enrollment: 44
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiolabeled monoclonal antibodies such as yttrium Y90 ibritumomab tiuxetan can locate cancer cells and deliver radioactive cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining yttrium Y90 ibritumomab tiuxetan and chemotherapy with autologous stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase I trial is studying how well giving yttrium Y90 ibritumomab tiuxetan with high-dose chemotherapy followed by autologous stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of yttrium Y 90 ibritumomab tiuxetan, in terms of absorbed radiation to critical organs, when administered with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.
* Determine whether the residual radioactivity detected at the time of stem cell reinfusion affects the reinfused cells and delays engraftment in patients treated with this regimen.
* Determine the duration of response and survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of yttrium Y 90 ibritumomab tiuxetan (IDEC-Y2B8).

* Radioimmunotherapy: Patients receive rituximab IV followed by indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -22. Patients then receive rituximab IV and IDEC-Y2B8 IV over 10 minutes on day -14.

Cohorts of 3-6 patients receive escalating doses of IDEC-Y2B8 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose-limiting toxicity.

* High-dose conditioning regimen: Patients receive BEAM chemotherapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 2 hours twice daily and cytarabine IV over 1 hour twice daily on days -5 to -2, and melphalan IV over 1 hour on day -1.
* Autologous stem cell transplantation: Autologous peripheral blood stem cells are reinfused on day 0. Patients receive filgrastim (G-CSF) subcutaneously daily beginning on day 0 and continuing until blood counts recover.

Patients are followed at 30 days, 3 and 6 months, and then annually for 5 years.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed B-cell non-Hodgkin's lymphoma

  * Relapsed or refractory disease
  * CD20-positive disease
* Must have received at least 1 prior treatment regimen
* Complete remission with prior conventional salvage chemotherapy is allowed
* No more than 25% lymphoma in bone marrow
* No circulating malignant cells on blood smear
* No CNS involvement by lymphoma
* No HIV- or AIDS-related lymphoma

PATIENT CHARACTERISTICS:

Age

* Over 17

Performance status

* ECOG 0-2

Life expectancy

* At least 3 months

Hematopoietic

* Platelet count at least 100,000/mm\^3
* Absolute neutrophil count at least 1,500/mm\^3

Hepatic

* Transaminases less than 2 times normal

Renal

* Creatinine clearance greater than 50 mL/min

Cardiovascular

* LVEF at least 45%

Pulmonary

* Corrected DLCO at least 70% of predicted
* FEV_1 or FVC greater than 60%

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No active infection
* No serious nonmalignant disease or other condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

* More than 4 weeks since prior rituximab and recovered
* No other prior murine antibodies
* No prior stem cell transplantation
* No prior radioimmunoconjugate therapy

Chemotherapy

* See Disease Characteristics
* More than 6 weeks since prior nitrosoureas or mitomycin and recovered

Endocrine therapy

* No concurrent systemic corticosteroids

Radiotherapy

* Recovered from prior radiotherapy
* No prior external beam irradiation to more than 25% of the active bone marrow

Surgery

* More than 4 weeks since prior major surgery and recovered

Other

* More than 3 weeks since prior anticancer therapy

Primary outcomes:
measure: Determine the maximum tolerated dose of absorbed radiation to critical organs delivered with this combination of study treatments
timeFrame: From first study treatment until 30 days after last study treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Hematology-Oncology Associates of Illinois
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Jane N. Winter, MD
role: STUDY_CHAIR
References:
citation: Winter J, Inwards D, Spies S, et al.: Zevalin® (90YZ) doses >.5 mCi/kg may be combined with high-dose beam and autotransplant (ASCT). [Abstract] Ann Oncol 16 (Suppl 5): A-215, v100, 2005.