Busulfan, Melphalan, and Thiotepa in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Hodgkin's or Non-Hodgkin's Lymphoma

Phase 2

Completed

Conditions: Lymphoma

Interventions: Biological: filgrastim
Drug: busulfan
Drug: melphalan
Drug: thiotepa
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation

Registration Number: NCT00238433

Lead Sponsor: OHSU Knight Cancer Institute

Brief Summary: RATIONALE: Chemotherapy, such as busulfan, melphalan, and thiotepa, may destroy cancerous blood-forming cells (stem cells) in the blood and bone marrow. Giving the patient their healthy stem cells will help their bone marrow make new stem cells that become red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well busulfan, melphalan, and thiotepa work in treating patients who are undergoing an autologous stem cell transplant for Hodgkin's or non-Hodgkin's lymphoma.

Detailed Description: OBJECTIVES:

* Determine the therapeutic efficacy of a myeloablative preparative regimen comprising busulfan, melphalan, and thiotepa followed by autologous peripheral blood stem cell (PBSC) transplantation in patients with Hodgkin's or non-Hodgkin's lymphoma.

* Determine the toxic effects of this preparative regimen in these patients.

OUTLINE:

* Myeloablative preparative regimen: Patients receive busulfan IV over 3 hours on days -8 to -6, melphalan IV over 15-30 minutes on days -5 and -4, and thiotepa IV over 2 hours on days -3 and -2.

* Peripheral blood stem cell (PBSC) transplantation: Patients undergo PBSC transplantation on day 0 followed by filgrastim (G-CSF) IV over 30 minutes beginning on day 5 and continuing until blood counts recover.

* Intrathecal chemotherapy: Patients with a history of treated Central Nervous System (CNS) disease or at high-risk for CNS relapse receive methotrexate and cytarabine intrathecally (IT) for 2 doses each within 10 days prior to transplantation and 4-6 doses each beginning on day 32 post-transplantation.

* Consolidation therapy: Patients with residual bulk disease at 80-100 days post-transplantation that is \> 2.5 cm by CT scan may undergo local radiotherapy to residual scar/disease provided it can be encompassed in a single radiation port and the volume of lung to be irradiated is ≤ 20%.

After completion of study treatment, patients are followed weekly for 1 month, monthly for 6 months, every 3 months for 6 months, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 37

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Filgrastim/Melphalan/Thiotepa	peripheral blood stem cell transplantation	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.
Filgrastim/Melphalan/Thiotepa	filgrastim	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.
Filgrastim/Melphalan/Thiotepa	bone marrow ablation with stem cell support	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.
Filgrastim/Melphalan/Thiotepa	busulfan	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.
Filgrastim/Melphalan/Thiotepa	melphalan	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.
Filgrastim/Melphalan/Thiotepa	thiotepa	Biological/Vaccine: filgrastim 5mcg/kg intravenous piggyback (IVPB) will be administered beginning on day +5 and continued until absolute neutrophil count (ANC) \> 1500 for 2 consecutive days. Drug: busulfan 3.2mg/kg/day for 3 days starting on day -8. Each dose of intravenous busulfan will be mixed in a concentration of 0.54 mg/ml of 0.9% saline and infused over 3 hours. Drug: melphalan 50mg/m2/day/iv, infused over 30 minutes on days -5 and -4. The reconstituted melphalan is diluted in 250cc normal saline to a concentration not greater than 0.4 mg/ml. Drug: thiotepa 250 mg/m2/day/iv on days -3 and -2 Procedure/Surgery: bone marrow ablation with stem cell support The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy. Procedure/Surgery: peripheral blood stem cell transplantation Performed 36-48 hours following last chemotherapy dose.

Primary Outcome Measures

Name	Time	Method
Disease-Free Survival	3, 6, 9, 12, 18, and 24 months post transplantation	The data presented below represents the total number of subjects (out of 36) that reached disease-free survival status during Months 3, 6, 9, 12, 18, and 24 time points.
Therapy-Related Toxicities	Through 24 months post transplantation	The table presented below reflects how many participants (out of 36 total) presented an adverse event related to the treatment regimen within each toxicity category. To review specific adverse events, both related and unrelated to study treatment, please refer to Adverse Events Section.

Secondary Outcome Measures