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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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ClinicalTrials.gov Identifier: NCT00238433
Recruitment Status : Completed
First Posted : October 13, 2005
Results First Posted : May 11, 2017
Last Update Posted : September 27, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Richard Maziarz, OHSU Knight Cancer Institute

Study Description
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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.


Condition or disease Intervention/treatment 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

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : March 2005
Actual Primary Completion Date : August 2015
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.

 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.


Outcome Measures
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Primary Outcome Measures :
  1. Disease-Free Survival [ Time Frame: 3, 6, 9, 12, 18, and 24 months post transplantation ]
    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.

  2. Therapy-Related Toxicities [ Time Frame: Through 24 months post transplantation ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   up to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00238433


Locations
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United States, Oregon
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States, 97239-3098
Sponsors and Collaborators
OHSU Knight Cancer Institute
National Cancer Institute (NCI)
Investigators
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Study Chair: Richard Maziarz, MD OHSU Knight Cancer Institute
More Information
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Responsible Party: Richard Maziarz, Principal Investigator, OHSU Knight Cancer Institute
ClinicalTrials.gov Identifier: NCT00238433    
Other Study ID Numbers: IRB00000248
P30CA069533 ( U.S. NIH Grant/Contract )
OHSU-HEM-04083-L
OHSU-IRB-248
First Posted: October 13, 2005    Key Record Dates
Results First Posted: May 11, 2017
Last Update Posted: September 27, 2017
Last Verified: September 2017
Keywords provided by Richard Maziarz, 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:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Melphalan
Busulfan
 Thiotepa
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Immunosuppressive Agents