Clinical trial NCT00049504: Haploidentical Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer
Official title: Nonmyeloablative Hematopoietic Stem Cell Transplantation for Patients With High-Risk Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Combined Immunosuppression Before and After Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Accelerated Phase Chronic Myelogenous Leukemia
Adult Acute Lymphoblastic Leukemia in Remission
Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Childhood Acute Lymphoblastic Leukemia in Remission
Childhood Acute Myeloid Leukemia in Remission
Childhood Burkitt Lymphoma
Childhood Chronic Myelogenous Leukemia
Childhood Myelodysplastic Syndromes
Childhood Nasal Type Extranodal NK/T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
de Novo Myelodysplastic Syndromes
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hematopoietic/Lymphoid Cancer
Hepatosplenic T-cell Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Peripheral T-cell Lymphoma
Post-transplant Lymphoproliferative Disorder
Previously Treated Myelodysplastic Syndromes
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Childhood Anaplastic Large Cell Lymphoma
Recurrent Childhood Grade III Lymphomatoid Granulomatosis
Recurrent Childhood Large Cell Lymphoma
Recurrent Childhood Lymphoblastic Lymphoma
Recurrent Childhood Small Noncleaved Cell Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Recurrent/Refractory Childhood Hodgkin Lymphoma
Refractory Chronic Lymphocytic Leukemia
Refractory Multiple Myeloma
Relapsing Chronic Myelogenous Leukemia
Secondary Myelodysplastic Syndromes
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage II Multiple Myeloma
Stage III Adult Burkitt Lymphoma
Stage III Adult Diffuse Large Cell Lymphoma
Stage III Adult Diffuse Mixed Cell Lymphoma
Stage III Adult Diffuse Small Cleaved Cell Lymphoma
Stage III Adult Hodgkin Lymphoma
Stage III Adult Immunoblastic Large Cell Lymphoma
Stage III Adult Lymphoblastic Lymphoma
Stage III Adult T-cell Leukemia/Lymphoma
Stage III Childhood Hodgkin Lymphoma
Stage III Chronic Lymphocytic Leukemia
Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
Stage III Grade 1 Follicular Lymphoma
Stage III Grade 2 Follicular Lymphoma
Stage III Grade 3 Follicular Lymphoma
Stage III Mantle Cell Lymphoma
Stage III Marginal Zone Lymphoma
Stage III Multiple Myeloma
Stage III Mycosis Fungoides/Sezary Syndrome
Stage III Small Lymphocytic Lymphoma
Stage IV Adult Burkitt Lymphoma
Stage IV Adult Diffuse Large Cell Lymphoma
Stage IV Adult Diffuse Mixed Cell Lymphoma
Stage IV Adult Diffuse Small Cleaved Cell Lymphoma
Stage IV Adult Hodgkin Lymphoma
Stage IV Adult Immunoblastic Large Cell Lymphoma
Stage IV Adult Lymphoblastic Lymphoma
Stage IV Adult T-cell Leukemia/Lymphoma
Stage IV Childhood Hodgkin Lymphoma
Stage IV Chronic Lymphocytic Leukemia
Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
Stage IV Grade 1 Follicular Lymphoma
Stage IV Grade 2 Follicular Lymphoma
Stage IV Grade 3 Follicular Lymphoma
Stage IV Mantle Cell Lymphoma
Stage IV Marginal Zone Lymphoma
Stage IV Mycosis Fungoides/Sezary Syndrome
Stage IV Small Lymphocytic Lymphoma
Testicular Lymphoma
Waldenström Macroglobulinemia
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 53
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II trial studies how well giving fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil and total-body irradiation together with a donor bone marrow transplant works in treating patients with high-risk hematologic cancer. Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells by stopping them from dividing or killing them. Giving cyclophosphamide after transplant may also stop the patient's immune system from rejecting the donor's bone marrow stem cells. The donated stem cells may replace the patient's immune system cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and mycophenolate mofetil after the transplant may stop this from happening

Detailed description: OBJECTIVES:

I. To determine if engraftment can be achieved safely in patients with high-risk hematologic malignancies who undergo non-myeloablative bone marrow transplantation (BMT) from human leukocyte antigen (HLA)-haploidentical donors.

OUTLINE:

NONMYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 1 hour on days -6 and -5. Patients undergo total body irradiation on day -1.

TRANSPLANTATION: Patients undergo BMT, from an HLA-haploidentical donor, on day 0.

POST-TRANSPLANT IMMUNOSUPPRESSION: Patients receive cyclophosphamide IV over 1 hour on day 3.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive tacrolimus IV over 1-2 hours and then tacrolimus orally (PO), once tolerated, on days 4-180, with taper on day 86 in the absence of graft-versus-host disease. Patients also receive mycophenolate mofetil PO three times daily on days 4-35.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

* Chronic myeloid leukemia (CML) in accelerated phase (AP)
* Acute myeloid leukemia (AML) with high-risk cytogenetics \[del(5q)/-5, del(7q)/-7, abnormal 3q, 9q, 11q, 20q, 21q, 17p, t(6:9), t(9;22), complex karyotypes (\>= 3 abnormalities)\] in complete remission (CR)1
* AML \>= CR2; patients should have \< 5% marrow blasts at the time of transplant
* High-risk ALL defined as: CR1 with high-risk cytogenetics; t(9;22), t(4;11), or hypodiploid (\< 45 chromosomes) for pediatric patients; t(9;22), t(8;14), t(4;11), t(1;19) for adult patients; \> 4 wk to achieve CR1; \>= CR2 (patients should have \< 5% marrow blasts at the time of transplant)
* Myelodysplastic syndromes (MDS) (\>int-1 per IPSS) after \>= 1 prior cycle of induction chemotherapy; should have \< 5% marrow blasts at the time of transplant
* Multiple myeloma (MM) Stage II or III patients who have progressed after an initial response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) or MM patients with refractory disease who may benefit from tandem autologous-nonmyeloablative allogeneic transplant
* Chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) or Hodgkin's Disease (HD) who are ineligible for autologous HSCT or who have resistant/refractory disease and who may benefit from tandem autologous nonmyeloablative allogeneic transplant
* Patients who have received a prior allogeneic HSCT and who have either rejected their grafts or who have become tolerant of their grafts with no active graft-versus-host disease (GvHD) requiring immunosuppressive therapy
* DONOR: Related donors who are identical for one HLA haplotype and mismatched at the HLA-A, -B, -C or DRB1 loci of the unshared haplotype with the exception of single HLA-A, -B or -C allele mismatches

Exclusion Criteria:

* Cross-match positive with donor
* Patients with suitably matched related or unrelated donors
* Patients with conventional transplant options (a conventional transplant should be the priority for eligible patients =\< 50 yr of age who have a related donor mismatched for a single HLA-A, -B or DRB1 antigen)
* Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
* Presence of active, serious infection (e.g., mucormycosis, uncontrolled aspergillosis, tuberculosis)
* Karnofsky Performance Status \< 60 for adult patients
* Lansky-Play Performance Score \< 60 for pediatric patients
* Left ventricular ejection fraction \< 35%
* Diffusing capacity of the lung for carbon monoxide (DLCO) \< 35% and/or receiving supplemental continuous oxygen
* Liver abnormalities: fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin \> 3 mg/dL or symptomatic biliary disease
* Human immunodeficiency virus (HIV)-positive patients
* Women of childbearing potential who are pregnant (beta-HCG+) or breast feeding
* Fertile men and women unwilling to use contraceptives during and for 12 months post-transplant
* Life expectancy severely limited by diseases other than malignancy
* DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the HVG direction
* DONOR: Cross-match positive with recipient

Primary outcomes:
measure: Donor Engraftment (Chimerism)
timeFrame: At day +84 after transplantation
measure: Incidence of Grades III-IV Acute GVHD
timeFrame: At any time within 200 days after transplantation
measure: Non-relapse-related Mortality
timeFrame: Up to 200 days after transplantation
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Paul O'Donnell
role: PRINCIPAL_INVESTIGATOR
References: