Bone Marrow Transplantation in Treating Patients With Hematologic Cancer

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00005804

Collaborator

National Cancer Institute (NCI) (NIH)

Location

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Precancerous/Nonmalignant Condition Small Intestine Cancer	Drug: cyclophosphamide Procedure: allogeneic bone marrow transplantation Radiation: radiation therapy	Phase 2

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 Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

Treatment of Patients With Hematological Malignancies Using Marrow Transplantation From Unrelated Donors Incompatible for One HLA Locus Antigen

Study Start Date :

Oct 1, 1999

Actual Primary Completion Date :

Aug 1, 2002

Actual Study Completion Date :

Aug 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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