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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00536601
First received: September 27, 2007
Last updated: March 25, 2014
Last verified: March 2014
  Purpose

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.


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

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Progression-free survival distribution of patients with HL, NHL, and MM for each disease-specific high-dose therapy regimen [ Time Frame: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years ] [ Designated as safety issue: No ]
    Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed based on Greenwood's formula for the variance of the survival function.


Secondary Outcome Measures:
  • Progression-free survival distribution of patients with amyloidosis, acute leukemia, and selected solid tumors for each disease-specific high-dose therapy regimen [ Time Frame: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years ] [ Designated as safety issue: No ]
    Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed based on Greenwood's formula for the variance of the survival function.

  • Regimen-related toxicity [ Time Frame: At 100 days ] [ Designated as safety issue: Yes ]
    Toxicities will be reported using descriptive statistics.

  • Response rate [ Time Frame: At 100 days ] [ Designated as safety issue: No ]
    Response rates will be reported using descriptive statistics.

  • Overall survival [ Time Frame: Up to 12 years ] [ Designated as safety issue: No ]
    Assessed using the product-limit based Kaplan Meier method.


Enrollment: 174
Study Start Date: June 2006
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen CBV (patients with HL or NHL)
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.
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: carmustine
Given IV
Other Names:
  • BCNU
  • BiCNU
  • bis-chloronitrosourea
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT
Experimental: Regimen M200/M120 (patients with MM or amyloidosis)
Patients receive 200 or 120 mg/m^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT
Experimental: Regimen BuC2iv (patients with ALL, AML, HL, or NHL)
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT
Experimental: Regimen CT6 (patients with ALL)
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT
Experimental: Regimen CTtCp (patients with other solid tumors)
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.
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Procedure: autologous hematopoietic stem cell transplantation
Undergo ASCT
Experimental: Regimen VCp (patients with testicular cancer)
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.
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Undergo tandem ASCT
Experimental: Regimen TtC1500/ECpM (patients with NBL or SRBCT)
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.
Drug: etoposide
Given IV
Other Names:
  • EPEG
  • VP-16
  • VP-16-213
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Drug: carboplatin
Given IV
Other Names:
  • Carboplat
  • CBDCA
  • JM-8
  • Paraplat
  • Paraplatin
Drug: thiotepa
Given IV
Other Names:
  • Oncotiotepa
  • STEPA
  • TESPA
  • Tespamin
  • TSPA
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Undergo tandem ASCT

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

Ages Eligible for Study:   4 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00536601

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Principal Investigator: Philip McCarthy Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00536601     History of Changes
Other Study ID Numbers: I 72806, NCI-2011-00131, I 72806, P30CA016056
Study First Received: September 27, 2007
Last Updated: March 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Congenital Abnormalities
Amyloidosis
Burkitt Lymphoma
Neoplasms
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neuroblastoma
Testicular Neoplasms
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Neoplasms, Germ Cell and Embryonal
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive

ClinicalTrials.gov processed this record on July 24, 2014