Clinical trial NCT00005804: Bone Marrow Transplantation in Treating Patients With Hematologic Cancer
Official title: Treatment of Patients With Hematological Malignancies Using Marrow Transplantation From Unrelated Donors Incompatible for One HLA Locus Antigen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Myeloproliferative Disorders
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Precancerous/Nonmalignant Condition
Small Intestine Cancer
Keywords: 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
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-08-28
Sex: ALL
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Claudio Anasetti, MD
role: STUDY_CHAIR
References: