High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

Not Applicable

Completed

Conditions: Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Childhood Acute Lymphoblastic Leukemia in Remission

Interventions: Drug: cyclophosphamide
Drug: etoposide
Drug: melphalan
Drug: busulfan
Radiation: total-body irradiation
Drug: carboplatin
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Drug: carmustine
Drug: thiotepa
Procedure: autologous hematopoietic stem cell transplantation

Registration Number: NCT00536601

Lead Sponsor: Roswell Park Cancer Institute

Brief Summary: This pilot trial studies different high-dose chemotherapy regimens with or without total-body irradiation (TBI) to compare how well they work when given before autologous stem cell transplant (ASCT) in treating patients with hematologic cancer or solid tumors. Giving high-dose chemotherapy with or without TBI before ASCT stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood or bone marrow and stored. More chemotherapy may be given to prepare for the stem cell transplant. The stem cells are then returned to the patient to replace the blood forming cells that were destroyed by the chemotherapy.

Detailed Description: PRIMARY OBJECTIVES:

I. Estimate the progression free survival (PFS) distribution for Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) for each disease-specific high dose therapy regimen.

SECONDARY OBJECTIVES:

I. Estimate the PFS distribution for amyloidosis, acute leukemia and selected solid tumors for each disease-specific high dose therapy regimen.

II. Explore the role of risk factors in the outcome of all treated patients. III. Examine the high dose therapy regimen-related toxicity (RRT) and overall survival after bone marrow transplant (BMT).

OUTLINE:

Patients are assigned to conditioning regimens based on disease, age, and co-morbidities.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 174

Inclusion Criteria

Histologically confirmed diagnosis of malignant hematologic disorders, amyloidosis or solid tumor malignancy
Recurrent or refractory disease or disease at high risk for recurrence
Hodgkin Disease (HL): Relapsed or refractory disease after chemotherapy with a minimum of one standard regimen
Non-Hodgkin Lymphoma (NHL): (Low, Intermediate or High Grade) Relapsed or refractory disease after chemotherapy with at least one standard regimen or first complete remission (CR) lymphoblastic or small, non-cleaved cell lymphoma at high risk of relapse by high International Prognostic Index (IPI) Score
Acute Myeloid Leukemia (AML): Low or High Risk disease in first or second CR or greater in patients in whom the risks of an allogeneic transplant outweigh the benefits
Acute Lymphoblastic Leukemia (ALL): Low or high risk disease in first or second CR in whom the risks of an allogeneic transplant outweigh the benefits
Multiple Myeloma (MM): Low or high risk in first or greater response (stable disease or better) or for responding patients at first progression
Other Malignant Lymphoproliferative Disorders: (chronic lymphocytic lymphoma [CLL], Waldenstroms macroglobulinemia, relapsed or refractory disease after first-line chemotherapy
Amyloidosis: primary or previously treated
Solid Tumors: Testicular cancer patients who have relapsed disease or primary progressive disease which is responding to salvage therapy; relapsed or advanced-stage newly diagnosed neuroblastoma (NBL) or small round blue cell tumors (SRBCT) in patients 30 years of age; other patients with solid tumors who have recurred following conventional treatment or are at high risk for relapse, and demonstrate chemosensitivity
Patients with malignancies who would be treated with an autologous stem cell transplant but have a syngeneic donor; a syngeneic donor would be considered to have the same risk as an autologous stem cell transplant patient
Performance status 0-2 (Karnofsky performance status [KPS] >= 70%); patients with amyloidosis or MM with decreased KPS due to disease are eligible
Life expectancy > 2 months
Pulmonary function tests; diffusing capacity of the lung for carbon monoxide (DLCO) or diffusing volume of the alveolar volume (DLVA) >= 50% predicted; DLCO to be corrected for hemoglobin and/or alveolar ventilation
Cardiac ventricular ejection fraction >= 50% by radionuclide ventriculogram or echocardiogram
Bilirubin < 3 x normal
Alkaline phosphatase, serum glutamic oxaloacetic transaminase (SGOT) < 3 x normal
Calculated creatinine clearance < 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
Glomerular filtration rate by renal scan for neuroblastoma patients, to determine dosing parameters
Positive cytomegalovirus (CMV) immunoglobulin M (IgM) and/or positive hepatitis serologies demonstrating infection will require an Infectious Disease consult and subsequent clearance
Any active infection will require an Infectious Disease consult and subsequent clearance
Peripheral Blood Counts of polymorphonuclear neutrophil (PMN) > 1500/uL
Platelet (Plt) > 75,000/uL
Prior to stem cell storage:
- No radiation within three weeks before stem cell harvest
- Bone marrow may be used in conjunction with blood progenitor cells
Hematologic Malignancy patients with human immunodeficiency virus (HIV) positivity but on appropriate anti-retroviral therapy may go autotransplant with the following laboratory tests; (CD4+ cell count > 75 cells per microliter and HIV copy number < 100,000 per microliter and with Infectious Disease clearance
Acute Leukemia, HL, NHL, MM and Solid Tumor patients must have received 2 cycles of chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells; small round blue cell tumor patients must have received either standard therapy or surgical intervention; the disease status and response to therapy must be known prior to transplant to establish the disease status at transplant; amyloidosis patients may proceed to BMT without receiving chemotherapy
No serious organ dysfunction unless it is caused by the underlying disease, exclusion criteria include the following:
- Uncontrolled or severe cardiovascular disease, including recent (< 6 months) myocardial infarction, congestive heart failure, symptomatic angina, life-threatening arrhythmia or hypertension
- Active bacterial, viral, or fungal infection
- Active peptic ulcer disease
- Uncontrolled diabetes mellitus
No serious medical or psychiatric illness
Not pregnant
No psychiatric conditions which would prevent delivery of care; psychology clearance is necessary
Allogeneic BMT not possible, or not desirable
- Age > 65 years
- No compatible donor identified
- Estimated risk of graft vs. host disease complications greater than risk of recurrence after autologous BMT
Adequate bone marrow or blood stem cell dose obtained:
- For blood stem cells: total CD 34+ >= 2 x 10^6/kg or if unable to collect this dose, a total nucleated cell bone marrow dose of >= l x 10^8/kg

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Regimen CBV (patients with HL or NHL)	autologous hematopoietic stem cell transplantation	Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
Regimen M200/M120 (patients with MM or amyloidosis)	autologous hematopoietic stem cell transplantation	Patients receive 200 or 120 mg/m\^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)	busulfan	Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)	autologous hematopoietic stem cell transplantation	Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
Regimen CT6 (patients with ALL)	cyclophosphamide	Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
Regimen CT6 (patients with ALL)	total-body irradiation	Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
Regimen CT6 (patients with ALL)	autologous hematopoietic stem cell transplantation	Patients receive cyclophosphamide IV over 2 hours on days -5 to -4. Patients then undergo TBI twice daily on days -3 to -1. Patients undergo ASCT on day 0.
Regimen CTtCp (patients with other solid tumors)	autologous hematopoietic stem cell transplantation	Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
Regimen VCp (patients with testicular cancer)	autologous-autologous tandem hematopoietic stem cell transplantation	Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	autologous-autologous tandem hematopoietic stem cell transplantation	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
Regimen CBV (patients with HL or NHL)	cyclophosphamide	Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
Regimen CBV (patients with HL or NHL)	etoposide	Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
Regimen CBV (patients with HL or NHL)	carmustine	Patients receive etoposide intravenously (IV) continuously over 34 hours on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3. Patients undergo ASCT on day 0.
Regimen M200/M120 (patients with MM or amyloidosis)	melphalan	Patients receive 200 or 120 mg/m\^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
Regimen BuC2iv (patients with ALL, AML, HL, or NHL)	cyclophosphamide	Patients receive busulfan IV over 2 hours then every 6 hours on days -7 to -4 for 16 total doses and cyclophosphamide IV over 2 hours on days -3 and -2. Patients undergo ASCT on day 0.
Regimen CTtCp (patients with other solid tumors)	carboplatin	Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
Regimen CTtCp (patients with other solid tumors)	cyclophosphamide	Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
Regimen CTtCp (patients with other solid tumors)	thiotepa	Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously over 24 hours on days -7 to -4. Patients undergo ASCT on day 0.
Regimen VCp (patients with testicular cancer)	etoposide	Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
Regimen VCp (patients with testicular cancer)	carboplatin	Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients then undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	cyclophosphamide	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	etoposide	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	melphalan	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	carboplatin	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.
Regimen TtC1500/ECpM (patients with NBL or SRBCT)	thiotepa	Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 2 hours on days -5 to -2. Patients undergo ASCT on day 0. At least 4 weeks after the first transplant, patients receive carboplatin IV continuously over 24 hours on days -7 to -4, etoposide IV continuously over 24 hours on days -7 to -4, and melphalan IV over 30 minutes on days -7 to -5. Patients undergo a second ASCT on day 0.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)	From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years	Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed.

Secondary Outcome Measures

Name	Time	Method
Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)	Patients are followed up to maximum of 12 years	Assessed using the product-limit based Kaplan Meier method.
Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal))	Up to 100 days after transplantation	Toxicities will be reported using descriptive statistics.
Response Rate (Complete Remission)	At 100 days	Response rates will be reported using descriptive statistics.