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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536601
• Other study ID #: I 72806
• Secondary ID: NCI-2011-00131I
• Status: Completed
• Phase: N/A
• Start date: June 29, 2006
• Est. completion date: July 9, 2018

Study information

• Verified date: March 2021
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: July 9, 2018
• Est. primary completion date: July 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Years and older

Eligibility

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

Related Conditions & MeSH terms

• 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
• Amyloidosis
• Burkitt 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
• Hodgkin Disease
• Immunoglobulin Light-chain Amyloidosis
• Intraocular Lymphoma
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Anaplastic
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Lymphomatoid Granulomatosis
• Multiple Myeloma
• Neoplasms
• Neoplasms, Plasma Cell
• Neuroblastoma
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Neuroectodermal Tumors, Primitive, Peripheral
• Nodal Marginal Zone B-cell Lymphoma
• Peripheral T-cell Lymphoma
• Plasma Cell Neoplasm
• Plasmablastic Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• 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
• Sarcoma
• Sarcoma, Ewing
• Splenic Marginal Zone Lymphoma
• Testicular Lymphoma
• Testicular Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific
• Unspecified Childhood Solid Tumor, Protocol Specific
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Drug:
• etoposide
Given IV
• cyclophosphamide
Given IV
• carmustine
Given IV
• melphalan
Given IV
• busulfan
Given IV
• carboplatin
Given IV
• thiotepa
Given IV

Radiation:
• total-body irradiation
Undergo TBI

Procedure:
• autologous hematopoietic stem cell transplantation
Undergo ASCT
• autologous-autologous tandem hematopoietic stem cell transplantation
Undergo tandem ASCT

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed.	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	Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal))	Toxicities will be reported using descriptive statistics.	Up to 100 days after transplantation
Secondary	Response Rate (Complete Remission)	Response rates will be reported using descriptive statistics.	At 100 days
Secondary	Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)	Assessed using the product-limit based Kaplan Meier method.	Patients are followed up to maximum of 12 years