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Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source


Phase 2
N/A
N/A
Open (Enrolling)
Both
Acute Undifferentiated Leukemia, Adult Acute Lymphoblastic Leukemia in Remission, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Myeloid Leukemia in Remission, Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Erythroleukemia (M6a), Adult Pure Erythroid Leukemia (M6b), Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Refractory Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source


PRIMARY OBJECTIVES:

I. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem
cells for nonmyeloablative transplants from related, haploidentical donors will not result
in unacceptable rates of high-grade acute or chronic GvHD, nonrelapse mortality (NRM) or
relapse compared to historical data on nonmyeloablative transplants from unrelated donors.

SECONDARY OBJECTIVES:

I. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell
(RBC) and platelet transfusions, incidences of graft failure, transplant-related toxicities,
disease-free survival and overall survival.

OUTLINE:

Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through
-2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo
total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell
transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice
daily on days 5-180 (may be continued if active GvHD is present), mycophenolate mofetil IV
or PO thrice daily (TID) on days 5-35 (may be continued if GvHD present), and filgrastim IV
or subcutaneously (SC) beginning on day 5 until the absolute neutrophil count (ANC) is >=
1,000/mm^3 for three consecutive days.

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


Inclusion Criteria:



- Molecular based human leukocyte antigens (HLA) typing will be performed for the
HLA-A, -B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish
haplo-identity; a minimum match of 5/10 is required

- An unrelated donor search is not required for a patient to be eligible for this
protocol if the clinical situation dictates an urgent transplant; clinical urgency is
defined as 6-8 weeks from referral or low-likelihood of finding a matched, unrelated
donor

- Acute leukemias (includes T lymphoblastic lymphoma) in remission

- Remission is defined as < 5% blasts with no morphological characteristics of acute
leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity, peripheral blood
counts showing ANC > 1000/ul, including patients in complete remission with
incomplete platelet recovery (CRp)

- Acute Lymphoblastic Leukemia in high risk first complete remission (CR1) as defined
by at least one of the following:

- Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), mixed lineage leukemia
(MLL) rearrangements

- White blood cell counts > 30,000/mcL

- Patients over 30 years of age

- Time to complete remission > 4 weeks

- Presence of extramedullary disease

- Acute Myelogenous Leukemia in high risk CR1 as defined by at least one of the
following:

- Greater than 1 cycle of induction therapy required to achieve remission

- Preceding myelodysplastic syndrome (MDS)

- Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities; or
French-American-British (FAB) M6 or M7 leukemia

- OR adverse cytogenetics for overall survival such as:

- Those associated with MDS

- Complex karyotype (>= 3 abnormalities); or

- Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with
other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)],
t(11;19)(q23;p13.1)

- Acute Leukemias in 2nd or subsequent remission

- Biphenotypic/Undifferentiated Leukemias in 1st or subsequent CR

- High-risk MDS status-post cytotoxic chemotherapy

- Burkitt's lymphoma: second or subsequent CR

- Chemotherapy-sensitive (complete or partial response) large cell, Mantle Cell or
Hodgkin's lymphomas that have failed at least 1 prior regimen of multi-agent
chemotherapy and are ineligible for an autologous transplant

- Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at
least two prior therapies (excluding single agent Rituxan)

- 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

- Left ventricular ejection fraction at rest must be >= 35%

- Bilirubin =< 2.5 mg/dL

- Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)

- Aspartate aminotransferase (AST) < 5 x ULN

- Alkaline phosphatase < 5 x ULN

- Serum creatinine within normal range for age, or if serum creatinine outside normal
range for age, then renal function (creatinine clearance or glomerular filtration
rate [GFR]) > 40 mL/min/1.73m^2

- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion
capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected
for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2)
saturation > 92% on room air

- Karnofsky/Lansky score >= 60%

- 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 GVHD requiring
immunosuppressive therapy

- DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient;
eligible donors include biological parents, siblings, or children, or half-siblings

- DONOR: Age >= 12 years

- DONOR: Weight >= 40 kg

- DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a
vascular access device; vein check must be performed and verified by an apheresis
nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)

- DONOR: Donors must meet the selection criteria as defined by the Foundation for the
Accreditation of Cell Therapy (FACT) and will be screened per the American
Association of Blood Banks (AABB) guidelines

Exclusion Criteria:

- HLA-matched or single allele-mismatched donor able to donate

- Pregnancy or breast-feeding

- Current uncontrolled bacterial, viral or fungal infection (currently taking
medication with evidence of progression of clinical symptoms or radiologic findings)

- Patients with primary idiopathic myelofibrosis

- DONOR: Positive anti-donor HLA antibody

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Incidence of grades III/IV acute GvHD

Outcome Description:

Grading determined by organ system stages. Grade III/IV acute GVHD is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.

Outcome Time Frame:

At day 84

Safety Issue:

No

Principal Investigator

Paul O'Donnell

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

2372.00

NCT ID:

NCT01028716

Start Date:

February 2010

Completion Date:

Related Keywords:

  • Acute Undifferentiated Leukemia
  • Adult Acute Lymphoblastic Leukemia in Remission
  • Adult Acute Megakaryoblastic Leukemia (M7)
  • Adult Acute Myeloid Leukemia in Remission
  • Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
  • Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
  • Adult Erythroleukemia (M6a)
  • Adult Pure Erythroid Leukemia (M6b)
  • Recurrent Adult Burkitt Lymphoma
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Adult Lymphoblastic Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Refractory Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Congenital Abnormalities
  • Burkitt Lymphoma
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Erythroblastic, Acute
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Megakaryoblastic, Acute
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Large B-Cell, Diffuse
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Lymphoma, Large-Cell, Immunoblastic
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Hematologic Neoplasms

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109