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

Roswell Park Comprehensive Cancer Center

Status

Completed

Conditions

Recurrent Neuroblastoma

Childhood Burkitt Lymphoma

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Splenic Marginal Zone Lymphoma

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Adult Acute Myeloid Leukemia in Remission

Recurrent Grade 3 Follicular Lymphoma

Recurrent Marginal Zone Lymphoma

Recurrent Adult Grade III Lymphomatoid Granulomatosis

Recurrent Grade 1 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Plasma Cell Neoplasm

Recurrent/Refractory Childhood Hodgkin Lymphoma

Primary Systemic Amyloidosis

Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)

Waldenström Macroglobulinemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Recurrent Small Lymphocytic Lymphoma

Recurrent Grade 2 Follicular Lymphoma

Recurrent Malignant Testicular Germ Cell Tumor

Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Nodal Marginal Zone B-cell Lymphoma

Recurrent Adult Burkitt Lymphoma

Recurrent Childhood Anaplastic Large Cell Lymphoma

Hepatosplenic T-cell Lymphoma

Adult Nasal Type Extranodal NK/T-cell Lymphoma

Recurrent Childhood Small Noncleaved Cell Lymphoma

Recurrent Childhood Grade III Lymphomatoid Granulomatosis

Childhood Immunoblastic Large Cell Lymphoma

Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor (PNET)

Regional Neuroblastoma

Recurrent Adult Hodgkin Lymphoma

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)

Refractory Multiple Myeloma

Recurrent Childhood Acute Lymphoblastic Leukemia

Recurrent Adult Diffuse Mixed Cell Lymphoma

Testicular Lymphoma

Recurrent Childhood Acute Myeloid Leukemia

Refractory Chronic Lymphocytic Leukemia

Recurrent Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Recurrent Adult Lymphoblastic Lymphoma

Intraocular Lymphoma

Adult Acute Myeloid Leukemia With Del(5q)

Childhood Nasal Type Extranodal NK/T-cell Lymphoma

Unspecified Adult Solid Tumor, Protocol Specific

Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)

Childhood Acute Myeloid Leukemia in Remission

Recurrent Adult Diffuse Large Cell Lymphoma

Adult Acute Lymphoblastic Leukemia in Remission

Childhood Acute Lymphoblastic Leukemia in Remission

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Recurrent Childhood Lymphoblastic Lymphoma

Childhood Diffuse Large Cell Lymphoma

Recurrent Childhood Large Cell Lymphoma

Recurrent Adult Acute Myeloid Leukemia

Unspecified Childhood Solid Tumor, Protocol Specific

Peripheral T-cell Lymphoma

Treatments

Drug: melphalan

Drug: etoposide

Radiation: total-body irradiation

Procedure: autologous hematopoietic stem cell transplantation

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Drug: busulfan

Drug: carmustine

Drug: thiotepa

Drug: carboplatin

Drug: cyclophosphamide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00536601

P30CA016056 (U.S. NIH Grant/Contract)

NCI-2011-00131 (Registry Identifier)

I 72806 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

174 patients

Sex

All

Ages

4+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

174 participants in 7 patient groups

Regimen CBV (patients with HL or NHL)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Drug: carmustine

Procedure: autologous hematopoietic stem cell transplantation

Drug: etoposide

Regimen M200/M120 (patients with MM or amyloidosis)

Experimental group

Description:

Patients receive 200 or 120 mg/m\^2 of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.

Treatment:

Procedure: autologous hematopoietic stem cell transplantation

Drug: melphalan

Regimen BuC2iv (patients with ALL, AML, HL, or NHL)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Procedure: autologous hematopoietic stem cell transplantation

Drug: busulfan

Regimen CT6 (patients with ALL)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Procedure: autologous hematopoietic stem cell transplantation

Radiation: total-body irradiation

Regimen CTtCp (patients with other solid tumors)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Drug: thiotepa

Drug: carboplatin

Procedure: autologous hematopoietic stem cell transplantation

Regimen VCp (patients with testicular cancer)

Experimental group

Description:

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.

Treatment:

Drug: carboplatin

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Drug: etoposide

Regimen TtC1500/ECpM (patients with NBL or SRBCT)

Experimental group

Description:

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.

Treatment:

Drug: cyclophosphamide

Drug: thiotepa

Drug: carboplatin

Procedure: autologous-autologous tandem hematopoietic stem cell transplantation

Drug: etoposide

Drug: melphalan

Trial documents