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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00238433
• Other study ID #: IRB00000248
• Secondary ID: P30CA069533OHSU-
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2005
• Last updated: September 25, 2017
• Start date: March 2005
• Est. completion date: December 2016

Study information

• Verified date: September 2017
• Source: OHSU Knight Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: December 2016
• Est. primary completion date: August 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• filgrastim
5mcg/kg IVPB will be administered beginning on day +5 and continued until 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.
• 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.
• thiotepa
250 mg/m2/day/iv on days -3 and -2

Procedure:
• 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.
• peripheral blood stem cell transplantation
Performed 36-48 hours following last chemotherapy dose.

Locations

Country	Name	City	State
United States	Knight Cancer Institute at Oregon Health and Science University	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
OHSU Knight Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	3, 6, 9, 12, 18, and 24 months post transplantation
Primary	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.	Through 24 months post transplantation