Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer - Full Text View

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00054327

Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor peripheral stem cell transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from a related donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

PURPOSE: This phase II trial is studying how well giving chemotherapy with or without radiation therapy followed by donor stem cell transplant works in treating patients with hematologic cancer.

Condition	Intervention	Phase
Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: busulfan Drug: cyclophosphamide Drug: cytarabine Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Hematopoietic Stem Cell Transplantation Using Bone Marrow Or Peripheral Blood Stem Cells From Matched, Unrelated, Volunteer Donors

Resource links provided by NLM:

MedlinePlus related topics: Anemia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Cyclophosphamide Busulfan Cytarabine hydrochloride Cytarabine

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:

Engraftment as measured by bone marrow biopsy [ Time Frame: days 28-35 after transplant ] [ Designated as safety issue: No ]
Toxicity as measured by CTC v2.0 [ Time Frame: weekly ] [ Designated as safety issue: Yes ]
Relapse rate [ Time Frame: measured at day 90 after transplantation, and then 1 and 2 years ] [ Designated as safety issue: No ]
Survival [ Time Frame: measured at day 90 after transplantation, and then 1 and 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Graft-versus-host disease [ Time Frame: measured weekly ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	November 2000
Estimated Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen A: Experimental Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.	Drug: cyclophosphamide Given IV Drug: cytarabine Given IV Radiation: radiation therapy Patients undergo radiation therapy
Regimen B: Experimental Patients receive cyclophosphamide IV and TBI as in regimen A.	Drug: cyclophosphamide Given IV Radiation: radiation therapy Patients undergo radiation therapy
Regimen B2: Experimental Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.	Drug: cyclophosphamide Given IV Radiation: radiation therapy Patients undergo radiation therapy
Regimen C: Experimental Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.	Drug: busulfan Given orally Drug: cyclophosphamide Given IV

Detailed Description:

OBJECTIVES:

Determine a standard approach to hematopoietic stem cell transplantation with matched unrelated donors in patients with hematologic malignancies.
Determine the toxicity of this regimen in these patients.
Determine the relapse rate and survival rate in patients treated with this regimen.
Correlate incidence and severity of graft-versus-host disease with relapse and survival in patients treated with this regimen.

OUTLINE: Patients receive 1 of the following preparative regimens:

Regimen A: Patients receive cytarabine IV over 1 hour twice daily on days -9 to -7 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients also undergo total body irradiation (TBI) twice daily on days -4 to -1.
Regimen B: Patients receive cyclophosphamide IV and TBI as in regimen A.
Regimen B2: Patients receive cyclophosphamide IV over 2 hours on days -5 and -4. Patients also undergo TBI twice daily on days -3 to -1.
Regimen C: Patients receive oral busulfan 4 times daily on days -8 to -5 and cyclophosphamide IV over 2 hours on days -4 to -2.

All patients undergo stem cell transplantation from a matched, unrelated donor on day 0.

Patients are followed weekly for 100 days, at 6 months, and then every 6 months for 2.5 years.

PROJECTED ACCRUAL: 50

Eligibility

Ages Eligible for Study:	up to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

One of the following histologically confirmed diseases:
- Acute myeloid leukemia (AML)
  - In first, second, or greater remission
  - In early relapse (less than 30% marrow blasts)
- Acute lymphoblastic leukemia (ALL)
  - In second or greater complete remission
  - High-risk ALL in first complete remission, defined by 1 of the following factors:
    - t(4;11), t(9;22), or t(8;14) translocation
    - Extreme hyperleukocytosis (WBC greater than 500,000/mL) at presentation
    - Failure to achieve a complete remission after standard induction therapy
- Chronic myelogenous leukemia
- Myelodysplastic syndromes
  - Evolution to AML included
    - Refractory anemia with excess blasts (RAEB)
    - RAEB in transformation
- Intermediate or high-grade lymphoma
  - Complete response (CR) or partial response (PR) after first or greater relapse OR
  - PR only after first-line therapy 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

55 and under

Performance status

ECOG 0-2 OR
Lansky 80-100%

Life expectancy

At least 3 months

Hematopoietic

See Disease Characteristics

Hepatic

Bilirubin less than 2.5 mg/dL
AST less than 4 times upper limit of normal
No chronic active hepatitis

Renal

Creatinine no greater than 2.0 mg/dL
Creatinine clearance at least 50 mL/min by 24-hour urine collection

Cardiovascular

Resting ejection fraction at least 50%
Shortening fraction greater than 28% (for small children)
No angina requiring treatment
No congestive heart failure requiring treatment
No myocardial infarction within the past year

Pulmonary

FEV_1 at least 50% of predicted
Arterial partial pressure of oxygen at least 80 mm Hg by pulmonary function testing
Diffusion capacity at least 50% of predicted

Other

Not pregnant or nursing
Negative pregnancy test
HIV negative
No uncontrolled diabetes mellitus
No active infection, including any of the following:
- Soft tissue infection
- Sinus infection
- Dental infection
- Fungal infection
No significant psychiatric illness that would preclude study participation
No medical complication that makes the risk of death during transplantation from nonmalignant causes greater than the risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy

At least 1 year since prior stem cell transplantation

Chemotherapy

See Disease Characteristics

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00054327

Locations

United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Geauga Regional Hospital
Cleveland, Ohio, United States, 44024
Lake/University Ireland Cancer Center
Cleveland, Ohio, United States, 44060
Mercy Cancer Center at Mercy Medical Center
Cleveland, Ohio, United States, 44708
Southwest General Health Center
Cleveland, Ohio, United States, 44130
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, United States, 44122
UHHS Westlake Medical Center
Cleveland, Ohio, United States, 44145
University Suburban Health Center
Cleveland, Ohio, United States, 44121

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Kenneth Cooke, MD

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center ( Kenneth Cooke, MD )
Study ID Numbers:	CWRU1Y00, P30CA043703, CASE-CWRU-1Y00
Study First Received:	February 5, 2003
Last Updated:	March 9, 2010
ClinicalTrials.gov Identifier:	NCT00054327 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:

adult acute myeloid leukemia in remission
childhood acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
childhood acute lymphoblastic leukemia in remission
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult Burkitt lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 3 follicular lymphoma

secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
recurrent childhood large cell lymphoma
recurrent childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
recurrent mantle cell lymphoma
refractory anemia with ringed sideroblasts
refractory anemia
chronic myelomonocytic leukemia
refractory cytopenia with multilineage dysplasia
previously treated myelodysplastic syndromes
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Leukemia
Preleukemia
Therapeutic Uses
Lymphoma
Alkylating Agents
Cytarabine

Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Hematologic Diseases
Myelodysplastic Syndromes
Myeloproliferative Disorders
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Bone Marrow Diseases
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on March 16, 2010