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

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
filgrastim
busulfan
melphalan
thiotepa
bone marrow ablation with stem cell support
peripheral blood stem cell transplantation
Sponsored by
OHSU Knight Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent adult Hodgkin lymphoma, recurrent adult diffuse small cleaved cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, recurrent adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent childhood anaplastic large cell lymphoma, stage III childhood anaplastic large cell lymphoma, stage IV childhood anaplastic large cell lymphoma, childhood grade III lymphomatoid granulomatosis, recurrent childhood large cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma

Eligibility Criteria

undefined - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Intermediate- or high-grade non-Hodgkin's lymphoma (NHL), meeting 1 of the following criteria: In first complete remission (CR) AND at high-risk for relapse, as defined by all of the following criteria: High age-adjusted International Prognostic Index category AND meets the following criteria at diagnosis: Stage III or IV disease Lactic dehydrogenase abnormal Eastern Cooperative Oncology Group (ECOG) score 0-2 Mantle cell histology Primary refractory disease Beyond first CR Low-grade NHL Beyond second relapse Hodgkin's lymphoma Primary refractory disease OR beyond first CR Must have an adequate number of stored autologous peripheral blood stem cells (PBSCs) (i.e., 2.0 x 10^6 hematopoietic progenitor cell antigen (CD34)-positive cells/kg) Patients who are not able to mobilize a sufficient number of PBSCs may use bone marrow instead No active CNS disease NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 0 to 70 Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin < 2 times upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN Renal Creatinine ≤ 2.0 mg/dL Creatinine clearance ≥ 50 mL/min Pulmonary No significant pulmonary dysfunction, defined as Diffusing Capacity the Lung for Carbon monoxide (DLCO) < 60% of predicted Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for ≥ 2 months before and during study participation HIV negative No significant active infection that would preclude PBSC transplantation PRIOR CONCURRENT THERAPY: Biologic therapy No prior transplantation No other concurrent blood products during PBSC transplantation Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy More than 60 days since prior local or regional radiotherapy Surgery Not specified Other More than 30 days since prior investigational drugs No concurrent amphotericin

Sites / Locations

  • Knight Cancer Institute at Oregon Health and Science University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Filgrastim/Melphalan/Thiotepa

Arm Description

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.

Outcomes

Primary Outcome Measures

Disease-Free Survival
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
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

Full Information

First Posted
October 12, 2005
Last Updated
September 25, 2017
Sponsor
OHSU Knight Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00238433
Brief Title
Busulfan, Melphalan, and Thiotepa in Treating Patients Who Are Undergoing an Autologous Stem Cell Transplant for Hodgkin's or Non-Hodgkin's Lymphoma
Official Title
A Phase II Study to Evaluate the Safety and Efficacy of IV Busulfan, Melphalan, and Thiotepa (BuMelTT) Followed By Autologous PBSC Infusion for Patients With Hodgkin's Disease and Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
March 2005 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
OHSU Knight Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
recurrent adult Hodgkin lymphoma, recurrent adult diffuse small cleaved cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, recurrent grade 3 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 3 follicular lymphoma, recurrent adult diffuse mixed cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage IV adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, stage III adult lymphoblastic lymphoma, stage IV adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage III adult Burkitt lymphoma, stage IV adult Burkitt lymphoma, recurrent mantle cell lymphoma, stage III mantle cell lymphoma, stage IV mantle cell lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, recurrent marginal zone lymphoma, splenic marginal zone lymphoma, recurrent small lymphocytic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent/refractory childhood Hodgkin lymphoma, stage III childhood Hodgkin lymphoma, stage IV childhood Hodgkin lymphoma, recurrent childhood anaplastic large cell lymphoma, stage III childhood anaplastic large cell lymphoma, stage IV childhood anaplastic large cell lymphoma, childhood grade III lymphomatoid granulomatosis, recurrent childhood large cell lymphoma, stage III childhood large cell lymphoma, stage IV childhood large cell lymphoma, recurrent childhood lymphoblastic lymphoma, stage III childhood lymphoblastic lymphoma, stage IV childhood lymphoblastic lymphoma, recurrent childhood small noncleaved cell lymphoma, stage III childhood small noncleaved cell lymphoma, stage IV childhood small noncleaved cell lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Filgrastim/Melphalan/Thiotepa
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
5mcg/kg IVPB will be administered beginning on day +5 and continued until ANC> 1500 for 2 consecutive days.
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
thiotepa
Intervention Description
250 mg/m2/day/iv on days -3 and -2
Intervention Type
Procedure
Intervention Name(s)
bone marrow ablation with stem cell support
Intervention Description
The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy.
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Description
Performed 36-48 hours following last chemotherapy dose.
Primary Outcome Measure Information:
Title
Disease-Free Survival
Description
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.
Time Frame
3, 6, 9, 12, 18, and 24 months post transplantation
Title
Therapy-Related Toxicities
Description
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.
Time Frame
Through 24 months post transplantation

10. Eligibility

Sex
All
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Intermediate- or high-grade non-Hodgkin's lymphoma (NHL), meeting 1 of the following criteria: In first complete remission (CR) AND at high-risk for relapse, as defined by all of the following criteria: High age-adjusted International Prognostic Index category AND meets the following criteria at diagnosis: Stage III or IV disease Lactic dehydrogenase abnormal Eastern Cooperative Oncology Group (ECOG) score 0-2 Mantle cell histology Primary refractory disease Beyond first CR Low-grade NHL Beyond second relapse Hodgkin's lymphoma Primary refractory disease OR beyond first CR Must have an adequate number of stored autologous peripheral blood stem cells (PBSCs) (i.e., 2.0 x 10^6 hematopoietic progenitor cell antigen (CD34)-positive cells/kg) Patients who are not able to mobilize a sufficient number of PBSCs may use bone marrow instead No active CNS disease NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 0 to 70 Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin < 2 times upper limit of normal (ULN) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times ULN Renal Creatinine ≤ 2.0 mg/dL Creatinine clearance ≥ 50 mL/min Pulmonary No significant pulmonary dysfunction, defined as Diffusing Capacity the Lung for Carbon monoxide (DLCO) < 60% of predicted Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception for ≥ 2 months before and during study participation HIV negative No significant active infection that would preclude PBSC transplantation PRIOR CONCURRENT THERAPY: Biologic therapy No prior transplantation No other concurrent blood products during PBSC transplantation Chemotherapy Not specified Endocrine therapy Not specified Radiotherapy More than 60 days since prior local or regional radiotherapy Surgery Not specified Other More than 30 days since prior investigational drugs No concurrent amphotericin
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Maziarz, MD
Organizational Affiliation
OHSU Knight Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Knight Cancer Institute at Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239-3098
Country
United States

12. IPD Sharing Statement

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

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