S0410 Tandem Stem Cell Transplantation in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

SWOG Cancer Research Network98 enrolled

Overview

RATIONALE: Radiation therapy uses high-energy x-rays to kill cancer cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Tandem (two) autologous stem cell transplants may be an effective treatment for Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well tandem stem cell transplantation works in treating patients with progressive or recurrent Hodgkin's lymphoma.

OBJECTIVES: * Determine the 2-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 multicenter study. * Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. No more than 6 weeks later, patients proceed to autologous hematopoietic stem cell collection. * 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. * Pre-transplant salvage radiation: Patients with residual tumor greater than 5 cm after initial salvage therapy undergo involved-field radiotherapy. All patients then proceed to the first preparative regimen. * First preparative regimen: Patients receive high-dose melphalan IV on day -1. * First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. At least 28 days later, patients proceed to second preparative regimen. * Second preparative regimen: Patients receive 1 of the following preparative regimens: * Total-body irradiation (TBI)-based regimen: Patients undergo TBI twice daily on days -8 to -5. Patients also receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 1 hour on day -2. * Carmustine-based regimen: Patients receive carmustine IV over 2 hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2. * Second autologous SCT: Patients undergo second autologous SCT on day 0. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 7 years. PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study over 2 years.

Study Type

Interventions

carmustineDRUG

150 mg/m\^2 IV over 2 hours 4, 5, and 6 days before transplant.

cyclophosphamideDRUG

100 mg/kg IV 2 days before transplant.

etoposideDRUG

60 mg/kg IV over 4 hours 4 days before transplant.

melphalanDRUG

150 mg/m\^2 IV 1 day before transplant.

autologous-autologous tandem hematopoietic stem cell transplantationPROCEDURE

2.0 x 10\^6 CD34+ cells, beginning at least 24 hours after melphalan infusion.

radiation therapyRADIATION

150 centigray (cGy) total body irradiation given b.i.d on days 5-8 before transplant.

Eligibility

Sex: ALLMin age: 15 YearsMax age: 70 Years

Medical Language ↔ Plain English

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed Hodgkin's lymphoma * Relapsed or refractory disease * Biopsy or radiological evidence of disease at time of recurrence/progression required * Has received ≥ 1 prior systemic chemotherapy regimen * No clonal abnormalities in marrow collection * Must undergo involved-field radiotherapy if bulky disease \> 5 cm * 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) * Patients who relapse after achieving a complete remission must complete a minimum of 2 courses of salvage chemotherapy or radiation therapy to determine if sensitive or resistant recurrent disease is present * No central nervous system (CNS) involvement PATIENT CHARACTERISTICS: Age * 15 to 70 Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 Hepatic * Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Hodgkin's disease) Renal * Creatinine clearance ≥ 60 mL/min * Creatinine ≤ 2 times upper limit of normal Cardiovascular * None of the following conditions requiring therapy: * Coronary artery disease * Cardiomyopathy * Congestive heart failure * Arrhythmias * Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram Pulmonary * Adequate pulmonary function * Corrected diffusing capacity of lung for carbon monoxide (DLCO) ≥ 60% OR * Forced Expiratory Volume in One Side (FEV\_1) ≥ 60% of predicted Other * Not pregnant or nursing * 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: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics Surgery * Not specified

Locations (53)

University of California Davis Cancer Center

Sacramento, California, United States

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

Cancer Center of Kansas, PA - Chanute

Chanute, Kansas, United States

Cancer Center of Kansas, PA - Dodge City

Dodge City, Kansas, United States

Outcomes

Primary Outcomes

2-year Progression-free Survival

Measured from date of randomization to date of first observation of progressive disease, or death due to any cause

Time frame: At day 60, then every 6 months for 2 years

Secondary Outcomes

Response Rate

Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

Time frame: At day 60, then every 6 months for 2 years

Overall Survival

Measured from date of registration to date of death due to any cause or last contact

Time frame: At day 60, then every 6 months for 2 years, then annually for a total of 7 years

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Time frame: Assessed after cycle 1 high dose therapy, after cycle 2 high dose therapy, and at 1 month and 2 months after the second stem cell infusion