Clinical trial NCT00536601: High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors
Official title: Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
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
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Diffuse Large Cell Lymphoma
Childhood Immunoblastic Large Cell Lymphoma
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET)
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Peripheral T-cell Lymphoma
Plasma Cell Neoplasm
Primary Systemic Amyloidosis
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Childhood Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Myeloid Leukemia
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Malignant Testicular Germ Cell Tumor
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Neuroblastoma
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Multiple Myeloma
Regional Neuroblastoma
Splenic Marginal Zone Lymphoma
Testicular Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Unspecified Childhood Solid Tumor, Protocol Specific
Waldenström Macroglobulinemia
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-09-28
Enrollment: 174
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years
Secondary outcomes:
measure: Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal))
timeFrame: Up to 100 days after transplantation
measure: Response Rate (Complete Remission)
timeFrame: At 100 days
measure: Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)
timeFrame: Patients are followed up to maximum of 12 years
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
Study officials:
affiliation: Roswell Park Cancer Institute
name: Philip McCarthy
role: PRINCIPAL_INVESTIGATOR
References: