Lymphoma
Conditions
Keywords
recurrent adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma
Brief summary
RATIONALE: Giving two autologous stem cell transplants (one after the other) may be an effective treatment for Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving two autologous stem cell transplants works in treating patients with progressive or recurrent Hodgkin's lymphoma.
Detailed description
OBJECTIVES: Primary * Determine the 3-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue). * Determine the response rate in patients treated with this regimen. * Determine the toxic effects of this regimen in these patients. OUTLINE: This is a pilot study. Patients are stratified according to risk (poor risk \[primary progressive, recurrent, or resistant relapse\] vs good risk \[first recurrence\]). * Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. * Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study. * First preparative regimen: Patients receive high-dose melphalan IV continuously over 16 hours on day -1. * First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. They also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. At least 4-8 weeks later, patients proceed to second preparative regimen. * Second preparative regimen: Patients receive high-dose carmustine IV over 1-2 hours on days -6, -5, and -4, etoposide IV over 4 hours on day -3, and cyclophosphamide IV over 2 hours on day -2. Beginning 36-48 hours later, patients proceed to the second autologous SCT (day 0). * Second autologous SCT: Patients undergo second autologous SCT on day 0. Patients also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.
Interventions
BIOLOGICALfilgrastim
480 mcg beginning day +5
DRUGbusulfan
11.2 mg/kg; 0.8 mg/kg IV q6h X 14 doses
DRUGcyclophosphamide
60 mg/kg IV over 2 hours x 2 days
DRUGetoposide
60 mg/kg, IV
DRUGmelphalan
150mg/m2 in NS at a concentration of 0.4mg/cc infused over 60 minutes.
autologous-autologous tandem hematopoietic stem cell transplantation
RADIATIONradiation therapy
radiation therapy
Sponsors
National Cancer Institute (NCI)
Case Comprehensive Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically\* confirmed Hodgkin's lymphoma meeting ≥ 1 of the following criteria: * Disease progression during initial first line chemotherapy * Complete response lasting ≤ 90 days after induction * Partial response lasting ≤ 90 days after induction * First recurrence/progression with the duration of initial response ≤ 12 months after completion of chemotherapy NOTE: \*There must be unequivocal radiological evidence of recurrent or progressive disease if biopsy was not obtained at time of disease recurrence/progression * No clonal abnormalities in marrow collection * Must have bilateral or unilateral bone marrow aspirates and biopsy within 42 days prior to stem cell collection * Must have adequate sections of original diagnostic specimen available for review * Needle aspirations or cytologies are not adequate * No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free ≥ 5 years) * No CNS involvement PATIENT CHARACTERISTICS: Performance status * Karnofsky 50-100% Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Bilirubin ≤ 1.5 times upper limit of normal\* (ULN) NOTE: \*Unless due to Hodgkin's lymphoma Renal * Creatinine clearance ≥ 60 mL/min * Creatinine ≤ 2.0 times ULN Cardiovascular * Ejection fraction ≥ 45% by 2-D echocardiogram * No significant active cardiac disease Pulmonary * Adequate pulmonary function * DLCO ≥ 45% Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer * No known HIV or AIDS infection * No active bacterial, fungal, or viral infection * No medical condition that would preclude study treatment PRIOR CONCURRENT THERAPY: Chemotherapy * See Disease Characteristics Surgery * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | one year after second transplant | Outcome is based on the number of patients who were alive without progression or relapse within 1 year. Progression is defined as a 50% increase in the sum of products of all measurable lesions. |
| Response Rate | One year after second transplant | Number of patients that receive a Complete Response (CR), Partial Response (PR)or Progression. CR defined as complete disappearance of all measurable and evaluable disease and no new lesions. PR is defined as \>/= 50% decrease in the sum of products of all measurable lesions. Progression is defined as a 50% increase in the sum of products of all measurable lesions. |
| Number of Patients That Experience Pulmonary Toxicity | One year after second transplant | Pulmonary toxicity are due to side effects that medicinal drugs cause to the lungs. |
Countries
United States
Participant flow
Recruitment details
Patients recruited from medical clinic from August 2002 thru October 2010.
Pre-assignment details
Only Poor Risk Patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Poor Risk Patients Poor Risk (primary progressive, recurrent, or resistant relapse) | 37 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Insurance denied the request | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | Poor Risk Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 35 Participants |
| Region of Enrollment United States | 37 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 23 / 37 |
| serious Total, serious adverse events | 1 / 37 |
Outcome results
Primary
Number of Patients That Experience Pulmonary Toxicity
Pulmonary toxicity are due to side effects that medicinal drugs cause to the lungs.
Time frame: One year after second transplant
Population: Analysis is per protocol, so includes patients who received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poor Risk Patients | Number of Patients That Experience Pulmonary Toxicity | 9 participants |
Primary
Progression-free Survival
Outcome is based on the number of patients who were alive without progression or relapse within 1 year. Progression is defined as a 50% increase in the sum of products of all measurable lesions.
Time frame: one year after second transplant
Population: Analysis is per protocol, so includes patients who received both transplants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Poor Risk Patients | Progression-free Survival | 18 participants |
Primary
Response Rate
Number of patients that receive a Complete Response (CR), Partial Response (PR)or Progression. CR defined as complete disappearance of all measurable and evaluable disease and no new lesions. PR is defined as \>/= 50% decrease in the sum of products of all measurable lesions. Progression is defined as a 50% increase in the sum of products of all measurable lesions.
Time frame: One year after second transplant
Population: Analysis is per protocol, so includes patients who received both transplants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Poor Risk Patients | Response Rate | Partial Response | 0 participants |
| Poor Risk Patients | Response Rate | Complete Response | 18 participants |
| Poor Risk Patients | Response Rate | Progression | 14 participants |
| Poor Risk Patients | Response Rate | Unknown | 2 participants |
| Poor Risk Patients | Response Rate | Expired | 3 participants |