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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00060255
• Other study ID #: CDR0000301587
• Secondary ID: RPCI-DS-9115
• Status: Completed
• Phase: Phase 2
• First received: May 6, 2003
• Last updated: May 7, 2013
• Start date: December 1991
• Est. completion date: February 2013

Study information

• Verified date: May 2013
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 451
• Est. completion date: February 2013
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 4 Years and older

Eligibility

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

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics

• More than 3 weeks since prior radiotherapy (before blood stem cell harvest)

• Prior cumulative doses of radiotherapy must not exceed the following:

• Spine/spinal cord: 4,000 cGy

• Mediastinum: 4,000 cGy

• Heart: 4,000 cGy

• Kidney (whole): 1,500 cGy

• Small bowel: 4,000 cGy

• Brain: 4,000 cGy

• Liver (whole): 2,000 cGy

• Lungs (whole): 1,500 cGy

• Bone: 5,000 cGy

Surgery

• Not specified

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Neoplasms
• Neoplasms, Germ Cell and Embryonal
• Neoplasms, Plasma Cell
• Plasmacytoma
• Testicular Germ Cell Tumor
• Testicular Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Drug:
• busulfan
iv
• carboplatin
iv
• carmustine
iv
• cyclophosphamide
iv
• etoposide
iv
• melphalan
oral
• thiotepa
iv

Procedure:
• autologous bone marrow transplantation
iv
• bone marrow ablation with stem cell support
iv
• peripheral blood stem cell transplantation
iv

Radiation:
• radiation therapy
body x-ray

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (1)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Morbidity		+day 100	No
Primary	Mortality		+day 100, +day 360	No
Primary	Overall outcome		every 6 months until death	No
Primary	Response rate		+day 100, +day 360	No
Primary	Toxicity		+day100, +day 360	Yes
Primary	Disease-free survival		up to 15years	No
Primary	Overall survival		every 6 months until death	No