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	Treatment or Intervention	Phase
Leukemia Lymphoma Multiple Myeloma Eye Cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: radiation therapy  Procedure: allogeneic bone marrow transplantation  Procedure: bone marrow transplantation  Drug: bone marrow ablation with stem cell support  Drug: cyclophosphamide	Phase II

Further Study Details: 

OBJECTIVES: I. 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. II. 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. III. Determine the relevance of HLA-DRB1 or DQB1 allele mismatching in BMT using donors matched for HLA-A, B, and C.

PROTOCOL 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.

Ages Eligible for Study:  up to  50 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--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 donor An 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

--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

--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

Washington
      Fred Hutchinson Cancer Research Center, Seattle,  Washington,  98109-1024,  United States

Study chairs or principal investigators

Claudio Anasetti,  Study Chair,  Fred Hutchinson Cancer Research Center   

Study ID Numbers:  CDR0000067780; FHCRC-1467.00; NCI-H00-0054
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  June 2, 2000
ClinicalTrials.gov Identifier:  NCT00005804
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08