Sargramostim Following Allogeneic Bone Marrow Transplantation in Treating Patients With Chronic Myelogenous Leukemia
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia |
Biological: sargramostim Biological: therapeutic allogeneic lymphocytes Procedure: allogeneic bone marrow transplantation Procedure: in vitro-treated bone marrow transplantation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| Official Title: | GRANULOCYTE-MACROPHAGE COLONY STIMULATING FACTOR (Rhu-GM-CSF) FOR REDUCTION OF LEUKEMIC RELAPSE AFTER T-LYMPHOCYTE DEPLETED ALLOGENEIC BMT FOR CHRONIC MYELOID LEUKEMIA |
| Estimated Enrollment: | 40 |
| Study Start Date: | February 1995 |
| Study Completion Date: | July 2010 |
| Primary Completion Date: | February 2005 (Final data collection date for primary outcome measure) |
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.
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| United States, Maryland | |
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | |
| Baltimore, Maryland, United States, 21231 | |
| Principal Investigator: | B. Douglas Smith, MD | Sidney Kimmel Comprehensive Cancer Center |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00002778 History of Changes |
| Other Study ID Numbers: | CDR0000064783, P01CA015396, P30CA006973, JHOC-J9449, BRLX-001.0649, JHOC-94110404, NCI-V96-0900 |
| Study First Received: | November 1, 1999 |
| Last Updated: | July 19, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
|
relapsing chronic myelogenous leukemia chronic phase chronic myelogenous leukemia accelerated phase chronic myelogenous leukemia |
Philadelphia chromosome positive chronic myelogenous leukemia Philadelphia chromosome negative chronic myelogenous leukemia atypical chronic myeloid leukemia |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Neoplasms by Histologic Type |
Neoplasms Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases |
ClinicalTrials.gov processed this record on May 22, 2013