Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
Treatment of Patients With Hematological Malignancies Using Marrow Transplantation From Unrelated Donors Incompatible for One HLA Locus Antigen
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 bone marrow transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation in treating patients who have hematologic cancer.
Study Overview
Status
Status
Conditions
Conditions
Intervention / Treatment
Intervention / Treatment
Detailed Description
OBJECTIVES:
- Compare the incidence of graft-versus-host disease (GVHD) grades III and IV in patients with hematologic malignancies treated with bone marrow transplantation (BMT) using donors with 1 HLA-A or B non-cross-reactive group mismatch vs control patients previously treated with BMT using donors with 1 HLA-A or B cross-reactive group (CREG) mismatch.
- Compare the incidence of GVHD grades III and IV in patients with hematologic malignancies treated with BMT using donors with 1 HLA-A or B CREG mismatch vs control patients previously treated with BMT using matched donors.
- Determine the relevance of HLA-DRB1 or DQB1 allele mismatching in BMT using donors matched for HLA-A, B, and C.
OUTLINE: Beginning at least 3 weeks after completion of cytoreductive combination chemotherapy, patients under age 18 undergo total body irradiation (TBI) twice a day on days -7 to -4. Patients age 18 and over undergo TBI twice a day on days -6 to -4. All patients then receive cyclophosphamide IV daily on days -3 and -2. Males with acute lymphocytic leukemia, high-grade lymphoma, intermediate-grade lymphoma, or marrow or CNS involvement receive radiotherapy boost to the testes. On day 0, patients receive infusion of bone marrow from unrelated donors with 1 of the following: 1 HLA-A or B non-cross-reactive group mismatch; 1 HLA-A or B cross-reactive group mismatch; or an HLA-A, B, and C match with an HLA-DRB1 or DQB1 mismatch.
Patients are followed every 6 months for 2 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study within 5 years.
Study Type
Study Type
Phase
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Washington
-
Seattle, Washington, United States, 98109-1024
- Fred Hutchinson Cancer Research Center
-
-
Participation Criteria
Eligibility Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
Histologically proven hematologic malignancy of 1 of the following types:
- Chronic myelogenous leukemia (CML) in chronic, accelerated, or blast* phase
Acute leukemia with high-risk features at diagnosis such as:
- Philadelphia chromosome-positive acute lymphocytic leukemia**
- Acute myeloid leukemia with high-risk cytogenetics such as inv (3), t(3;3) del(5q), -5, del(7q), -7, +8, +11, abnormal 12p, del(20q), -20, or complex abnormalities**
- Acute leukemia with failure after one course of induction chemotherapy
- Acute leukemia in first relapse* or second remission
- High-risk lymphoblastic lymphoma in first remission
- Non-Hodgkin's lymphoma, Hodgkin's disease, or other malignant lymphoproliferative disease after first remission, if an autologous transplantation is not indicated
- Myelodysplastic or myeloproliferative syndromes ineligible for Protocol FHCRC-179 NOTE: * For patients with acute leukemia in relapse or CML in blast crisis, the search for an unrelated donor begins only if: High probability that the patient's medical condition will remain stable for the 3 to 6-month period needed to find a donorAn attempt at remission induction has been undertaken Referring physician and patient accept possibility that search for donor will be canceled if patient's condition worsens
NOTE: ** For newly diagnosed patients with high-risk acute leukemia, early referral is encouraged so that an unrelated donor search may begin immediately
Availability of an unrelated donor with:
- 1 HLA-A or B non-cross-reactive group (non-CREG) mismatch (except in CML in chronic phase or myelodysplastic syndrome) OR
- 1 HLA-A or B CREG mismatch OR
An HLA-A, B, and C match with an HLA-DRB1 or DQB1 mismatch (no double mismatch) if 1 of the above 2 donor types unavailable
- No more than 1 HLA-A, B, and C mismatch
No availability of an HLA-identical sibling or haploidentical relative incompatible for 0 or 1 HLA-A or B locus of the nonshared haplotypes
- For patients with diagnosis other than CML in chronic phase, 1 HLA-DR locus-incompatible related donor has priority over an HLA compatible or class IA or B CREG locus antigen-incompatible unrelated donor
- No severe aplastic anemia
- No leukoencephalopathy
PATIENT CHARACTERISTICS:
Age:
- Under 51
- Eligible for transplantation until age 52 if the donor is identified prior to patient's 51st birthday
Performance status:
- Not specified
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- No severe hepatic disease, including acute hepatitis
Renal:
- Creatinine less than 2 times normal
Cardiovascular:
- No cardiac insufficiency requiring treatment
- No symptomatic coronary artery disease
Pulmonary:
- No severe hypoxemia (i.e., PO2 less than 70 mm Hg) with decreased DLCO (i.e., DLCO less than 70% predicted) OR
- No mild hypoxemia (i.e., PO2 less than 80 mm Hg) with severely decreased DLCO (i.e., DLCO less than 60% predicted)
- No pulmonary fibrosis
Other:
- No other nonmalignant disease that would severely limit life expectancy
- HIV negative
- No contraindication to total body irradiation (TBI)
- Patients excluded from this study because of contraindication to TBI may be treated on protocol FHCRC-739
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- Not specified
Radiotherapy:
- No prior radiotherapy greater than 3,000 cGy to whole brain
- At least 6 months since prior involved-field radiotherapy greater than 1,500 cGy to chest or abdomen
Surgery:
- Not specified
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
Collaborators and Investigators
Sponsor
Sponsor
Collaborators
Collaborators
Investigators
Investigators
- Study Chair: Claudio Anasetti, MD, Fred Hutchinson Cancer Center
Study record dates
Study Major Dates
Study Start
Study Start
Primary Completion (Actual)
Primary Completion
Study Completion (Actual)
Study Completion
Study Registration Dates
First Submitted
First Submitted
First Submitted That Met QC Criteria
First Submitted That Met QC Criteria
First Posted (Estimate)
First Posted
Study Record Updates
Last Update Posted (Estimate)
Last Update Posted
Last Update Submitted That Met QC Criteria
Last Update Submitted That Met QC Criteria
Last Verified
Last Verified
More Information
Terms related to this study
Keywords
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult Burkitt lymphoma
- recurrent childhood small noncleaved cell lymphoma
- recurrent childhood large cell lymphoma
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- chronic phase chronic myelogenous leukemia
- childhood myelodysplastic syndromes
- primary systemic amyloidosis
- recurrent adult acute myeloid leukemia
- untreated adult acute myeloid leukemia
- untreated childhood acute lymphoblastic leukemia
- adult acute myeloid leukemia in remission
- recurrent adult Hodgkin lymphoma
- childhood immunoblastic large cell lymphoma
- recurrent/refractory childhood Hodgkin lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- blastic phase chronic myelogenous leukemia
- Waldenstrom macroglobulinemia
- stage III multiple myeloma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent mantle cell lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- small intestine lymphoma
- stage III adult lymphoblastic lymphoma
- stage IV adult lymphoblastic lymphoma
- recurrent adult T-cell leukemia/lymphoma
- intraocular lymphoma
- angioimmunoblastic T-cell lymphoma
- anaplastic large cell lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- refractory multiple myeloma
- recurrent adult acute lymphoblastic leukemia
- polycythemia vera
- essential thrombocythemia
- refractory hairy cell leukemia
- prolymphocytic leukemia
- monoclonal gammopathy of undetermined significance
- recurrent childhood acute lymphoblastic leukemia
- stage II childhood lymphoblastic lymphoma
- stage III childhood lymphoblastic lymphoma
- stage IV childhood lymphoblastic lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- accelerated phase chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- recurrent childhood acute myeloid leukemia
- recurrent childhood lymphoblastic lymphoma
- isolated plasmacytoma of bone
- extramedullary plasmacytoma
- chronic idiopathic myelofibrosis
- acute undifferentiated leukemia
- untreated adult acute lymphoblastic leukemia
- progressive hairy cell leukemia, initial treatment
- T-cell large granular lymphocyte leukemia
- untreated childhood acute myeloid leukemia and other myeloid malignancies
- contiguous stage II adult lymphoblastic lymphoma
- Burkitt lymphoma
Additional Relevant MeSH Terms
- Digestive System Diseases
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Hemorrhagic Disorders
- Intestinal Diseases
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Lymphoma
- Syndrome
- Myelodysplastic Syndromes
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Leukemia
- Preleukemia
- Plasmacytoma
- Intestinal Neoplasms
- Myeloproliferative Disorders
- Precancerous Conditions
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
Other Study ID Numbers
Other Study ID Numbers
- 1467.00
- FHCRC-1467.00
- NCI-H00-0054
- CDR0000067780 (Registry Identifier: PDQ)
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