Sargramostim Following Allogeneic Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia

NCT ID: NCT00002778

Last Updated: 2011-07-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-02-28
• Study Completion Date: 2010-07-31

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with allogeneic bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Colony-stimulating factors such as sargramostim may increase the number of immune cells found in bone marrow or peripheral blood, and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to study the effectiveness of allogeneic bone marrow transplantation followed by sargramostim in treating patients who have chronic myelogenous leukemia.

Detailed Description

OBJECTIVES:

• Determine whether the use of sargramostim (GM-CSF) after T-cell depleted, CD34-positive cell-supplemented allogeneic bone marrow transplantation can reduce leukemic relapse in patients with chronic myelogenous leukemia.

OUTLINE: Patients receive myeloablation with busulfan and cyclophosphamide on an approved protocol. Allogeneic bone marrow is harvested and treated in vitro with anti-CD34 antibody. T-cell depleted, CD34-positive cell-supplemented bone marrow is infused on day 0. Patients receive high-dose sargramostim (GM-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover and then low-dose GM-CSF SC continuing until day 60.

Donor lymphocyte infusions or second unmodified allogeneic bone marrow transplantation without GM-CSF is considered in case of primary or secondary engraftment failure.

Patients are followed every month for 3 months, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within approximately 6-10 years.

Conditions

Leukemia

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

sargramostim

Intervention Type: BIOLOGICAL

therapeutic allogeneic lymphocytes

Intervention Type: BIOLOGICAL

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

in vitro-treated bone marrow transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of chronic myelogenous leukemia (CML) documented by cytogenetic and molecular analyses at Johns Hopkins

• Philadelphia chromosome (Ph)-positive or -negative CML

• Ph-negative CML allowed with presence of either:

• BCR-ABL rearrangement (on molecular, fluorescent in situ hybridization, or polymerase chain reaction analyses)
• p210 protein
• One of the following:

• Patient age 18 to 65
• Disease duration longer than 3 years
• Accelerated phase CML
• Accelerated phase diagnosis based on any of the following:

• More than 10% to less than 30% blasts in blood or bone marrow
• No hematologic response to prior conventional therapy (hydroxyurea or interferon)
• Extramedullary disease (e.g., progressive splenomegaly or lymphadenopathy)
• Basophilia greater than 10% in blood or bone marrow
• Other cytogenetic abnormalities in addition to a single Ph chromosome
• Second chronic phase
• Failure on interferon suggested of patients over age 18 with chronic phase CML, with failure defined as:

• No detectable Ph-negative metaphases in marrow after 6 months
• No progressive increase in Ph-negative metaphases in marrow after 6-12 months
• Less than 50% Ph-negative metaphases after 1 year
• No complete cytogenetic remission after 2 years
• Intolerance to interferon therapy
• No blast crisis CML, chronic myelomonocytic leukemia, or juvenile CML
• The following conditions are allowed:

• Leukocyte count abnormalities
• Fibrosis
• Anemia
• Fever or bone pain
• Thrombocytopenia
• Bone marrow reticulin
• Availability of an HLA-identical sibling donor

• At least 3 years of age (priority given to donors over age 10)
• Priority given to CMV-negative donor if patient CMV-negative
• No medical or psychiatric condition that precludes transplant procedure

PATIENT CHARACTERISTICS:

Age

• 18 to 65

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Not specified

Renal

• Not specified

Other

• No history of intolerance to sargramostim (GM-CSF)

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Principal Investigators

B. Douglas Smith, MD

Role: PRINCIPAL_INVESTIGATOR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

P01CA015396

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA006973

Identifier Type: NIH

Identifier Source: secondary_id

View Link

JHOC-J9449

Identifier Type: -

Identifier Source: secondary_id

BRLX-001.0649

Identifier Type: -

Identifier Source: secondary_id

JHOC-94110404

Identifier Type: -

Identifier Source: secondary_id

NCI-V96-0900

Identifier Type: -

Identifier Source: secondary_id

CDR0000064783

Identifier Type: -

Identifier Source: org_study_id