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

NCT ID: NCT00536601

Last Updated: 2021-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 174 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-06-29
• Study Completion Date: 2018-07-09

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

etoposide

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

carmustine

Intervention Type: DRUG

Given IV

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo ASCT

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.

Group Type: EXPERIMENTAL

melphalan

Intervention Type: DRUG

Given IV

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo ASCT

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

busulfan

Intervention Type: DRUG

Given IV

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo ASCT

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

total-body irradiation

Intervention Type: RADIATION

Undergo TBI

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo ASCT

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

thiotepa

Intervention Type: DRUG

Given IV

autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo ASCT

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.

Group Type: EXPERIMENTAL

etoposide

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

autologous-autologous tandem hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo tandem ASCT

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.

Group Type: EXPERIMENTAL

etoposide

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

melphalan

Intervention Type: DRUG

Given IV

carboplatin

Intervention Type: DRUG

Given IV

thiotepa

Intervention Type: DRUG

Given IV

autologous-autologous tandem hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo tandem ASCT

Interventions

etoposide

Given IV

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

carmustine

Given IV

Intervention Type: DRUG

melphalan

Given IV

Intervention Type: DRUG

busulfan

Given IV

Intervention Type: DRUG

carboplatin

Given IV

Intervention Type: DRUG

thiotepa

Given IV

Intervention Type: DRUG

total-body irradiation

Undergo TBI

Intervention Type: RADIATION

autologous hematopoietic stem cell transplantation

Undergo ASCT

Intervention Type: PROCEDURE

autologous-autologous tandem hematopoietic stem cell transplantation

Undergo tandem ASCT

Intervention Type: PROCEDURE

Other Intervention Names

EPEG; VP-16; VP-16-213; CPM; CTX; Cytoxan; Endoxan; Endoxana; BCNU; BiCNU; bis-chloronitrosourea; Alkeran; CB-3025; L-PAM; L-phenylalanine mustard; L-Sarcolysin; BSF; BU; Misulfan; Mitosan; Myeloleukon; Carboplat; CBDCA; JM-8; Paraplat; Paraplatin; Oncotiotepa; STEPA; TESPA; Tespamin; TSPA; TBI

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 4 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip McCarthy

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

Roswell Park Cancer Institute

Buffalo, New York, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2011-00131

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 72806

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016056

Identifier Type: NIH

Identifier Source: secondary_id

View Link

I 72806

Identifier Type: -

Identifier Source: org_study_id