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


Phase 2
N/A
50 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Precancerous/Nonmalignant Condition, Small Intestine Cancer

Thank you

Trial Information

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


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.

Inclusion 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 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Claudio Anasetti, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1467.00

NCT ID:

NCT00005804

Start Date:

October 1999

Completion Date:

August 2002

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • Precancerous/Nonmalignant Condition
  • Small Intestine Cancer
  • monoclonal gammopathy of undetermined significance
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent adult Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • Burkitt lymphoma
  • isolated plasmacytoma of bone
  • extramedullary plasmacytoma
  • refractory multiple myeloma
  • Waldenstrom macroglobulinemia
  • stage III multiple myeloma
  • stage II childhood lymphoblastic lymphoma
  • stage III childhood lymphoblastic lymphoma
  • stage IV childhood lymphoblastic lymphoma
  • recurrent childhood lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent adult acute lymphoblastic leukemia
  • small intestine lymphoma
  • childhood immunoblastic large cell lymphoma
  • chronic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • untreated adult acute lymphoblastic leukemia
  • untreated adult acute myeloid leukemia
  • untreated childhood acute myeloid leukemia and other myeloid malignancies
  • untreated childhood acute lymphoblastic leukemia
  • adult acute myeloid leukemia in remission
  • adult acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • polycythemia vera
  • chronic idiopathic myelofibrosis
  • essential thrombocythemia
  • progressive hairy cell leukemia, initial treatment
  • refractory hairy cell leukemia
  • recurrent/refractory childhood Hodgkin lymphoma
  • chronic myelomonocytic leukemia
  • T-cell large granular lymphocyte leukemia
  • acute undifferentiated leukemia
  • stage III adult lymphoblastic lymphoma
  • stage IV adult lymphoblastic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent adult Burkitt lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • secondary acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • prolymphocytic leukemia
  • primary systemic amyloidosis
  • intraocular lymphoma
  • recurrent childhood small noncleaved cell lymphoma
  • recurrent childhood large cell lymphoma
  • contiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • recurrent mantle cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • anaplastic large cell lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • 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
  • childhood myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Precancerous Conditions
  • Lymphoma, Large-Cell, Immunoblastic
  • Duodenal Neoplasms
  • Ileal Neoplasms
  • Jejunal Neoplasms
  • Intestinal Neoplasms

Name

Location
Fred Hutchinson Cancer Research Center Seattle, Washington  98109