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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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lymphoma |
Biological: filgrastim Drug: busulfan Drug: melphalan Drug: thiotepa Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Disease-free survival at 3, 6, 9, 12, 18, and 24 months post transplantation [ Time Frame: 3, 6, 9, 12, 18, and 24 months post transplantation ] [ Designated as safety issue: No ]
- Regimen-related toxicity through 24 months post transplantation [ Time Frame: Through 24 months post transplantation ] [ Designated as safety issue: Yes ]
| Enrollment: | 37 |
| Study Start Date: | March 2005 |
| Estimated Primary Completion Date: | January 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Filgrastim/Melphalan/Thiotepa
Biological/Vaccine: 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. 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. |
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.
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: 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: peripheral blood stem cell transplantation
Performed 36-48 hours following last chemotherapy dose.
|
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 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| Ages Eligible for Study: | up to 70 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
- ECOG 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 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)
- AST and ALT < 3 times ULN
Renal
- Creatinine ≤ 2.0 mg/dL
- Creatinine clearance ≥ 50 mL/min
Pulmonary
- No significant pulmonary dysfunction, defined as 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
Contacts and Locations| United States, Oregon | |
| Knight Cancer Institute at Oregon Health and Science University | |
| Portland, Oregon, United States, 97239-3098 | |
| Study Chair: | Richard Maziarz, MD | OHSU Knight Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | OHSU Knight Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00238433 History of Changes |
| Other Study ID Numbers: | CDR0000446086, P30CA069533, OHSU-HEM-04083-L, OHSU-IRB-248 |
| Study First Received: | October 12, 2005 |
| Last Updated: | May 10, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by OHSU Knight Cancer Institute:
|
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 |
Additional relevant MeSH terms:
|
Lymphoma Lymphoma, Non-Hodgkin Lymphoma, Large-Cell, Immunoblastic Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Busulfan Melphalan Thiotepa |
Lenograstim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Therapeutic Uses Myeloablative Agonists Adjuvants, Immunologic |
ClinicalTrials.gov processed this record on May 21, 2013