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Phase II Study of High-Dose Chemotherapy, Total Body Irradiation, and Autologous Peripheral Blood or Bone Marrow Transplantation in Patients With Hematologic Malignancies or Selected Chemosensitive Solid Tumors

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
Phase II Treatment Closed 4 and over (4 to 59 if receiving TBI) NCI RPCI-DS-9115
NCT00060255

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.

Entry Criteria

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.]

Prior/Concurrent Therapy:

Biologic therapy

See Disease Characteristics

Chemotherapy

See Disease Characteristics
No prior cumulative nitrosourea dose greater than 600 mg/m²
No prior cumulative bleomycin dose greater than 150 units/m²
No prior cumulative doxorubicin dose greater than 450 mg/m²
No prior cumulative daunorubicin dose greater than 600 mg/m²
Patients with prior high-dose cyclophosphamide (greater than 150 mg/kg per cycle) and high-dose etoposide (greater than 2,400 mg/m² 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

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/mm³*
Polymorphonuclear leukocyte count greater than 1,500/mm³*
Platelet count greater than 75,000/mm³*
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

Expected Enrollment

450

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

Outcomes

Primary Outcome(s)

Morbidity
Mortality
Overall outcome
Response rate
Toxicity
Disease-free survival
Overall survival

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.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Philip McCarthy, MD, Protocol chair
Ph: 716-845-4074; 800-685-6825
Email: philip.mccarthy@roswellpark.org

Registry Information

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

Trial Start Date		1991-07-30

Registered in ClinicalTrials.gov		NCT00060255

Date Submitted to PDQ		2003-03-26

Information Last Verified		2006-10-13

NCI Grant/Contract Number		CA16056

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.