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

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.

• etoposide (Drug), also known as EPEG, VP-16, VP-16-213: Given IV
• cyclophosphamide (Drug), also known as CPM, CTX, Cytoxan, Endoxan, Endoxana: Given IV
• carmustine (Drug), also known as BCNU, BiCNU, bis-chloronitrosourea: Given IV
• melphalan (Drug), also known as Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin: Given IV
• busulfan (Drug), also known as BSF, BU, Misulfan, Mitosan, Myeloleukon: Given IV
• carboplatin (Drug), also known as Carboplat, CBDCA, JM-8, Paraplat, Paraplatin: Given IV
• thiotepa (Drug), also known as Oncotiotepa, STEPA, TESPA, Tespamin, TSPA: Given IV
• total-body irradiation (Radiation), also known as TBI: Undergo TBI
• autologous hematopoietic stem cell transplantation (Procedure): Undergo ASCT
• autologous-autologous tandem hematopoietic stem cell transplantation (Procedure): Undergo tandem ASCT

Primary outcomes

• 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) [From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years]: Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed.

Secondary outcomes

• Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal)) [Up to 100 days after transplantation]: Toxicities will be reported using descriptive statistics.
• Response Rate (Complete Remission) [At 100 days]: Response rates will be reported using descriptive statistics.
• Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors) [Patients are followed up to maximum of 12 years]: Assessed using the product-limit based Kaplan Meier method.

Sex: All, ages: 4 Years to any

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

Participant flow

Outcome results

• 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) (Primary), Number, Proportion of participants: Acute Leukemia 33 (0 to 71); Hodgkin Lymphoma 14 (0 to 40); Non-Hodgkin Lymphoma 22 (7 to 38); MM/Amyloid ; Solid Tumors
• Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal)) (Secondary), Count of participants, Participants: Acute Leukemia 1; Hodgkin Lymphoma 9; Non-Hodgkin Lymphoma 19; MM/Amyloid 31; Solid Tumors 3
• Response Rate (Complete Remission) (Secondary), Count of participants, Participants: Acute Leukemia 5; Hodgkin Lymphoma 17; Non-Hodgkin Lymphoma 54; MM/Amyloid 17; Solid Tumors 7
• Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors) (Secondary), Number, Proportion of participants: Acute Leukemia 33 (0 to 71); Hodgkin Lymphoma 61 (40 to 82); Non-Hodgkin Lymphoma 45 (33 to 57); MM/Amyloid 39 (27 to 51); Solid Tumors 46 (16 to 75)

Adverse events

Time frame: SAE= 100 days after transplantation All cause mortality = 12 years

Serious adverse events by term

• Study Protocol and Statistical Analysis Plan (PDF, 2018-02-06)

• Philip McCarthy, Principal investigator, Roswell Park Cancer Institute

NIH grants: P30CA016056