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

Sponsor

Northwestern University (Other)

Overall Status

Completed

CT.gov ID

NCT00058292

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

107

Duration (Months)

14.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: Carmustine Drug: cytarabine Drug: etoposide Drug: melphalan Procedure: peripheral blood stem cell transplantation Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2000

Actual Primary Completion Date :

Jun 1, 2006

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm	Biological: filgrastim Given at a dose of 5 μg/kg, subcutaneously daily, beginning on Day 0 (stem cell transplant day) until white blood cells measure greater than 1500/ul. Other Names: G-CSF granulocyte colony stimulating factor Biological: rituximab Intravenous infusion of 250 mg/m2 on treatment days -22 and -14 (day 0 = stem cell transplant). Drug: Carmustine Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Carmustine is given at a dose of 300 mg/m2 intravenous infusion over a 2 hour period on treatment day -6 (Day 0 = stem cell transplant). Other Names: BCNU Drug: cytarabine Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Cytarabine is given at a dose of 100 mg/m2 intravenous infusion over a 1 hour period, every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant). Other Names: Cytosar-U Arabinosyl Ara-C cytosine arabinoside Drug: etoposide Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Etoposide is given at a dose of 100 mg/m2 intravenous infusion over a 2 hour period every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant). Other Names: VP-16 VP-16-213 Vepesid Epidophylotoxin Drug: melphalan Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Melphalan is given at a dose of 140 mg/m2 as an intravenous infusion over a 1 hour period on treatment day -1 (Day 0 = stem cell transplant). Procedure: peripheral blood stem cell transplantation On day 0, a minimum of 2.0 X 106 CD34+ cells/kg unselected peripheral blood progenitor cells (PBPC) will be reinfused following institutional guidelines for the reinfusion procedure. Radiation: yttrium Y 90 ibritumomab tiuxetan Patients will receive 90Y2B8 at a variable dose on treatment day -14 (Day 0 = stell cell transplant). The initial dose calculated to deliver no more than 100 cGy to critical organs (liver, lung). Doses will be escalated based on cohort of enrollment.

Arm

Intervention/Treatment

Experimental: Treatment Arm

Biological: filgrastim

Given at a dose of 5 μg/kg, subcutaneously daily, beginning on Day 0 (stem cell transplant day) until white blood cells measure greater than 1500/ul.

Other Names:

G-CSF

granulocyte colony stimulating factor

Biological: rituximab

Intravenous infusion of 250 mg/m2 on treatment days -22 and -14 (day 0 = stem cell transplant).

Drug: Carmustine

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Carmustine is given at a dose of 300 mg/m2 intravenous infusion over a 2 hour period on treatment day -6 (Day 0 = stem cell transplant).

Other Names:

BCNU

Drug: cytarabine

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Cytarabine is given at a dose of 100 mg/m2 intravenous infusion over a 1 hour period, every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant).

Other Names:

Cytosar-U

Arabinosyl

Ara-C

cytosine arabinoside

Drug: etoposide

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Etoposide is given at a dose of 100 mg/m2 intravenous infusion over a 2 hour period every 12 hours on treatment days -5, -4, -3, and -2, for a total of 8 doses (Day 0 = stem cell transplant).

Other Names:

VP-16

VP-16-213

Vepesid

Epidophylotoxin

Drug: melphalan

Part of high dose BEAM chemotherapy given on study (a combination of carmustine, etoposide, cytarabine, and melphalan). Melphalan is given at a dose of 140 mg/m2 as an intravenous infusion over a 1 hour period on treatment day -1 (Day 0 = stem cell transplant).

Procedure: peripheral blood stem cell transplantation

On day 0, a minimum of 2.0 X 106 CD34+ cells/kg unselected peripheral blood progenitor cells (PBPC) will be reinfused following institutional guidelines for the reinfusion procedure.

Radiation: yttrium Y 90 ibritumomab tiuxetan

Patients will receive 90Y2B8 at a variable dose on treatment day -14 (Day 0 = stell cell transplant). The initial dose calculated to deliver no more than 100 cGy to critical organs (liver, lung). Doses will be escalated based on cohort of enrollment.

Outcome Measures

Primary Outcome Measures

Determine the maximum tolerated dose of absorbed radiation to critical organs delivered with this combination of study treatments [From first study treatment until 30 days after last study treatment.]
Dose limiting toxicities observed during and up to 30 days after the last study treatment resulting in the determination of the maximum tolerated dose of absorbed radiation to critical organs delivered by Y2B8 in combination with high-dose BEAM chemotherapy with autologous mobilized peripheral blood progenitor cell transplant

Eligibility Criteria

Criteria

Ages Eligible for Study:

17 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hematology-Oncology Associates of Illinois	Chicago	Illinois	United States	60611-2998
2	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
3	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905