Lymphoma
Conditions
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
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.
Interventions
BIOLOGICALfilgrastim
5mcg/kg IVPB will be administered beginning on day +5 and continued until ANC\> 1500 for 2 consecutive days.
DRUGbusulfan
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.
DRUGmelphalan
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.
DRUGthiotepa
250 mg/m2/day/iv on days -3 and -2
PROCEDUREbone 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.
PROCEDUREperipheral blood stem cell transplantation
Performed 36-48 hours following last chemotherapy dose.
Sponsors
National Cancer Institute (NCI)
OHSU Knight Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival | 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. |
| Therapy-Related Toxicities | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Busulfan/Melphalan/Thiotepa Treatment Plan:
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: Peripheral blood stem cell transplantation. Performed 36-48 hours following last chemotherapy dose.
The transplant therapy should begin within 2 weeks of registration, but no sooner then 30 days after the last dose of chemotherapy.
Administration Growth Factor: Filgrastim 5mcg/kg IVPB will be administered beginning on day +5 and continued until ANC\> 1500 for 2 consecutive days. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Screen failure | 1 |
Baseline characteristics
| Characteristic | Busulfan/Melphalan/Thiotepa |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Region of Enrollment United States | 36 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 36 / 36 |
| serious Total, serious adverse events | 36 / 36 |
Outcome results
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.
Time frame: 3, 6, 9, 12, 18, and 24 months post transplantation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 3 months | 34 Participants |
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 6 months | 30 Participants |
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 9 months | 28 Participants |
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 12 months | 25 Participants |
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 18 months | 24 Participants |
| Busulfan/Melphalan/Thiotepa | Disease-Free Survival | 24 months | 22 Participants |
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.
Time frame: Through 24 months post transplantation
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Dermatological Toxicities | 3 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Gastrointestinal Toxicities | 26 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Immune System Toxicites | 1 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Infections | 33 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Metabolic Toxicities | 3 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Respiratory Toxicities | 2 Participants |
| Busulfan/Melphalan/Thiotepa | Therapy-Related Toxicities | Vascular Toxicities | 1 Participants |