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

NCT ID: NCT00238433

Last Updated: 2017-09-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-03-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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.

Conditions

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Lymphoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Filgrastim/Melphalan/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.

Group Type EXPERIMENTAL

filgrastim

Intervention Type BIOLOGICAL

5mcg/kg IVPB will be administered beginning on day +5 and continued until ANC\> 1500 for 2 consecutive days.

busulfan

Intervention Type DRUG

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.

melphalan

Intervention Type DRUG

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.

thiotepa

Intervention Type DRUG

250 mg/m2/day/iv on days -3 and -2

bone marrow ablation with stem cell support

Intervention Type PROCEDURE

The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy.

peripheral blood stem cell transplantation

Intervention Type PROCEDURE

Performed 36-48 hours following last chemotherapy dose.

Interventions

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filgrastim

5mcg/kg IVPB will be administered beginning on day +5 and continued until ANC\> 1500 for 2 consecutive days.

Intervention Type BIOLOGICAL

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.

Intervention Type 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.

Intervention Type DRUG

thiotepa

250 mg/m2/day/iv on days -3 and -2

Intervention Type DRUG

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.

Intervention Type PROCEDURE

peripheral blood stem cell transplantation

Performed 36-48 hours following last chemotherapy dose.

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion 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
Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Richard Maziarz

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Richard Maziarz, MD

Role: STUDY_CHAIR

OHSU Knight Cancer Institute

Locations

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Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, United States

Site Status

Countries

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United States

Other Identifiers

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P30CA069533

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OHSU-HEM-04083-L

Identifier Type: -

Identifier Source: secondary_id

OHSU-IRB-248

Identifier Type: -

Identifier Source: secondary_id

IRB00000248

Identifier Type: -

Identifier Source: org_study_id