Clinical trial NCT00238433: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: OHSU Knight Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-10-13
Enrollment: 37
Sex: ALL
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Disease-Free Survival
timeFrame: 3, 6, 9, 12, 18, and 24 months post transplantation
measure: Therapy-Related Toxicities
timeFrame: Through 24 months post transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Portland
country: United States
facility: Knight Cancer Institute at Oregon Health and Science University
state: Oregon
Study officials:
affiliation: OHSU Knight Cancer Institute
name: Richard Maziarz, MD
role: STUDY_CHAIR
References: