High-Dose Chemotherapy, Total-Body Irradiation, and Autologous Stem Cell Transplantation or Bone Marrow Transplantation in Treating Patients With Hematologic Cancer or Solid Tumors

Sponsor

Roswell Park Cancer Institute (Other)

Overall Status

Completed

CT.gov ID

NCT00060255

Collaborator

(none)

451

Enrollment

Location

254.1

Duration (Months)

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to damage cancer cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation or autologous bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well eight different high-dose chemotherapy regimens with or without total-body irradiation followed by autologous stem cell transplantation or autologous bone marrow transplantation works in treating patients with hematologic malignancies or solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Testicular Germ Cell Tumor Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific	Drug: busulfan Drug: carboplatin Drug: carmustine Drug: cyclophosphamide Drug: etoposide Drug: melphalan Drug: thiotepa Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 2

Detailed Description

OBJECTIVES:

Determine the morbidity, mortality, and overall outcome in patients with hematologic malignancies, breast cancer, or other chemosensitive solid tumors treated with disease-specific dose-intensive conditioning regimens and autologous peripheral blood or bone marrow transplantation.

OUTLINE: Patients are stratified according to risk group (standard vs high). Standard risk includes acute leukemia in first relapse or second remission; lymphoma in responding first relapse or second remission; or breast cancer at risk for recurrence. High risk includes all others. Patients receive specific conditioning regimens according to diagnosis as outlined below.

Conditioning

Regimen A (standard risk non-Hodgkin's lymphoma and under 60 years of age)-Etoposide, cyclophosphamide, and total body irradiation (TBI) (VCT): Patients receive etoposide IV continuously over 26 hours beginning on day -5 and cyclophosphamide IV over 2 hours on day -4. Patients undergo TBI on days -3 to -1.
Regimen B (any risk Hodgkin's lymphoma and under 60 years of age)-Cyclophosphamide, carmustine, and etoposide (CBV): Patients receive etoposide IV continuously over 34 hours beginning on day -8; cyclophosphamide IV over 2 hours on days -7 to -4; and carmustine IV over 2 hours on day -3.
Regimen C (any risk patient with prior exposure to high-dose etoposide and cyclophosphamide and under 60 years of age)-Melphalan and TBI (MEL/TBI): Patients receive melphalan IV over 30 minutes on day -4. Patients undergo TBI on days -3 to -1.
Regimen D (multiple myeloma or amyloidosis)-Melphalan only (MEL only): Patients receive melphalan IV over 30 minutes on day -2.
Regimen E (any patient unable to receive TBI)-Busulfan and cyclophosphamide: Patients receive oral busulfan (or busulfan IV over 2 hours) on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2.
Regimen F (any risk breast cancer)-Cyclophosphamide, carboplatin, and thiotepa (STAMP V): Patients receive cyclophosphamide IV over 24 hours, carboplatin IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.
Regimen G (solid tumors other than breast or testicular cancer)-Thiotepa and carboplatin (TT/CARBO): Patients receive thiotepa IV over 2 hours on days -6 and -5 and carboplatin IV continuously over 96 hours beginning on day -6.
Regimen H (recurrent or primary progressive testicular cancer)-Etoposide and carboplatin (VP/CARBO): Patients receive etoposide IV over 2 hours and carboplatin IV over 30 minutes on days -6 to -4.

Stem Cell Infusion

In all regimens, patients undergo autologous stem cell infusion on day 0. Treatment continues in the absence of unacceptable toxicity.

PROJECTED ACCRUAL: Approximately 450 patients (50 patients [25 per stratum] per regimen) will be accrued for this study within 10 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

451 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 1991

Actual Primary Completion Date :

Aug 1, 2006

Actual Study Completion Date :

Feb 1, 2013

Outcome Measures

Primary Outcome Measures

Morbidity [+day 100]
Mortality [+day 100, +day 360]
Overall outcome [every 6 months until death]
Response rate [+day 100, +day 360]
Toxicity [+day100, +day 360]
Disease-free survival [up to 15years]
Overall survival [every 6 months until death]

Eligibility Criteria

Criteria

Ages Eligible for Study:

4 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed hematologic or solid tumor malignancy, including any of the following:
Acute myeloid leukemia
First remission and not eligible for allogeneic transplantation; recurrent disease after combination chemotherapy with at least 1 standard regimen; or second remission
Not eligible for protocol CLB-9620 or CLB-9621
Acute lymphoblastic leukemia
First complete remission without appropriate allogeneic donor
Chronic myelogenous leukemia
Chronic, accelerated, or blast phase
Lymphoproliferative diseases*
Chronic lymphocytic leukemia
Multiple myeloma
Waldenstrom's macroglobulinemia
Low-grade non-Hodgkin's lymphoma (NHL) NOTE: *Recurrent or persistent, symptomatic disease after first-line chemotherapy, or subsequently
Amyloidosis
Primary or previously treated disease
NHL (intermediate- and high-grade)
Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen
First remission lymphoblastic or small, non-cleaved cell lymphoma at high risk of relapse
CNS disease OR bone marrow disease and lactic dehydrogenase greater than 300 IU/L
Hodgkin's lymphoma
Resistant or recurrent disease after combination chemotherapy with at least 1 standard regimen
Solid tumors
High-risk and metastatic breast cancer
Testicular cancer that has relapsed OR primary progressive disease that is responding to salvage therapy
Other solid tumors that have recurred after conventional therapy OR are at high risk for relapse, and demonstrate chemosensitivity
Less than 10% marrow tumor present histologically (maximum of 15% involvement allowed if purged)
Allogeneic marrow transplantation not possible or not desirable for any of the following reasons:
Over 60 years of age
No compatible donor identified
Estimated risk of graft-versus-host disease complications greater than risk of recurrence after autologous bone marrow transplantation
Patients with disease progression in a site of prior radiotherapy (4,000 cGy or more) are not eligible for total body irradiation (TBI) regimens
Hormone receptor status:
Not specified NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.

PATIENT CHARACTERISTICS:

Age

4 and over (patients 60 years of age and over are not eligible for TBI)

Sex

Male or female

Menopausal status

Not specified

Performance status

Karnofsky 70-100%

Life expectancy

More than 2 months

Hematopoietic

WBC greater than 3,000/mm^3*
Polymorphonuclear leukocyte count greater than 1,500/mm^3*
Platelet count greater than 75,000/mm^3*
Marrow cellularity greater than 20%*
No marrow fibrosis* NOTE: *Before marrow storage

Hepatic

Bilirubin less than 3 times normal
Alkaline phosphatase less than 3 times normal
AST less than 3 times normal
Hepatitis status known

Renal

Creatinine clearance at least 50 mL/min (not required for patients with amyloidosis or multiple myeloma)

Cardiovascular

Ventricular ejection fraction at least 50% by radionuclide ventriculogram or echocardiogram
No myocardial infarction within the past 6 months
No congestive heart failure
No symptomatic angina
No life-threatening arrhythmia or hypertension

Pulmonary

DLCO or DLVA at least 50% of predicted (DLCO must be corrected for hemoglobin and/or alveolar ventilation)

Other

Not pregnant
HIV negative
Cytomegalovirus status known
No active bacterial, viral, or fungal infection
No active peptic ulcer disease
No uncontrolled diabetes mellitus
No serious organ dysfunction unless it is caused by the underlying disease
No other serious medical or psychiatric illness that would preclude giving informed consent or complying with study requirements

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics
No prior cumulative nitrosourea dose greater than 600 mg/m^2
No prior cumulative bleomycin dose greater than 150 units/m^2
No prior cumulative doxorubicin dose greater than 450 mg/m^2
No prior cumulative daunorubicin dose greater than 600 mg/m^2
Patients with prior high-dose cyclophosphamide (greater than 150 mg/kg per cycle) and high-dose etoposide (greater than 2,400 mg/m^2 per cycle) are not eligible for the etoposide/cyclophosphamide/TBI conditioning regimen