Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies

Case Comprehensive Cancer Center (Case CCC)

Status and phase

Completed

Phase 2

Conditions

Cutaneous B-cell Non-Hodgkin Lymphoma

T-cell Large Granular Lymphocyte Leukemia

Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue

Splenic Marginal Zone Lymphoma

Recurrent Adult Diffuse Small Cleaved Cell Lymphoma

Adult Acute Myeloid Leukemia in Remission

Recurrent Grade 3 Follicular Lymphoma

B-cell Childhood Acute Lymphoblastic Leukemia

Recurrent Marginal Zone Lymphoma

Childhood Myelodysplastic Syndromes

Recurrent Adult Grade III Lymphomatoid Granulomatosis

Recurrent Grade 1 Follicular Lymphoma

Recurrent Mantle Cell Lymphoma

Childhood Acute Minimally Differentiated Myeloid Leukemia (M0)

Blastic Phase Chronic Myelogenous Leukemia

Stage III Chronic Lymphocytic Leukemia

Adult Acute Minimally Differentiated Myeloid Leukemia (M0)

Adult Acute Monocytic Leukemia (M5b)

T-cell Adult Acute Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Childhood Chronic Myelogenous Leukemia

Adult Acute Megakaryoblastic Leukemia (M7)

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities

Recurrent Small Lymphocytic Lymphoma

Childhood Acute Monocytic Leukemia (M5b)

Recurrent Grade 2 Follicular Lymphoma

Juvenile Myelomonocytic Leukemia

Childhood Acute Monoblastic Leukemia (M5a)

Nodal Marginal Zone B-cell Lymphoma

Recurrent Adult Burkitt Lymphoma

Secondary Myelofibrosis

Recurrent Childhood Anaplastic Large Cell Lymphoma

Recurrent Mycosis Fungoides/Sezary Syndrome

Chronic Phase Chronic Myelogenous Leukemia

Adult Nasal Type Extranodal NK/T-cell Lymphoma

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome

Recurrent Childhood Small Noncleaved Cell Lymphoma

Recurrent Childhood Grade III Lymphomatoid Granulomatosis

Childhood Immunoblastic Large Cell Lymphoma

Childhood Acute Erythroleukemia (M6)

Waldenstrom Macroglobulinemia

Stage I Chronic Lymphocytic Leukemia

Adult Pure Erythroid Leukemia (M6b)

Recurrent Childhood Acute Lymphoblastic Leukemia

Previously Treated Myelodysplastic Syndromes

Relapsing Chronic Myelogenous Leukemia

Adult Acute Monoblastic Leukemia (M5a)

Recurrent Adult Diffuse Mixed Cell Lymphoma

Recurrent Childhood Acute Myeloid Leukemia

Refractory Chronic Lymphocytic Leukemia

Recurrent Adult Immunoblastic Large Cell Lymphoma

Recurrent Adult Acute Lymphoblastic Leukemia

Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma

Recurrent Adult Lymphoblastic Lymphoma

Burkitt Lymphoma

Prolymphocytic Leukemia

Childhood Nasal Type Extranodal NK/T-cell Lymphoma

Adult Erythroleukemia (M6a)

de Novo Myelodysplastic Syndromes

Childhood Acute Myeloid Leukemia in Remission

Recurrent Adult Diffuse Large Cell Lymphoma

Adult Acute Lymphoblastic Leukemia in Remission

Stage II Chronic Lymphocytic Leukemia

Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable

Secondary Myelodysplastic Syndromes

Childhood Acute Lymphoblastic Leukemia in Remission

B-cell Adult Acute Lymphoblastic Leukemia

Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)

Childhood Acute Megakaryocytic Leukemia (M7)

Recurrent Childhood Lymphoblastic Lymphoma

Childhood Diffuse Large Cell Lymphoma

Stage IV Chronic Lymphocytic Leukemia

Secondary Acute Myeloid Leukemia

Recurrent Childhood Large Cell Lymphoma

Recurrent Adult Acute Myeloid Leukemia

T-cell Childhood Acute Lymphoblastic Leukemia

Treatments

Drug: cyclophosphamide

Other: flow cytometry

Procedure: allogeneic hematopoietic stem cell transplantation

Procedure: bone marrow aspiration

Other: cytogenetic analysis

Drug: methylprednisolone

Drug: cyclosporine

Drug: mycophenolate mofetil

Other: fluorescence in situ hybridization

Procedure: double-unit umbilical cord blood transplantation

Drug: anti-thymocyte globulin

Drug: busulfan

Study type

Interventional

Funder types

Other

Identifiers

NCT01093586

NCI-2009-01319 (Other Identifier)

CASE3Z07 (Other Identifier)

Details and patient eligibility

About

RATIONALE: Giving chemotherapy before a donor umbilical cord blood transplant (UCBT) helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the stem cells from an unrelated donor, that do not exactly match the patient's blood, are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before transplant and cyclosporine and mycophenolate mofetil after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor umbilical cord blood stem cell transplant works in treating patients with hematologic malignancies.

Full description

PRIMARY OBJECTIVES:

To establish the day +180 overall survival after a myeloablative unrelated double unit UCBT in a single institution setting.

SECONDARY OBJECTIVES:

To determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies, who are undergoing myeloablative chemotherapy followed by infusion of double unit UCBT.
To determine the contribution of each umbilical cord unit to immune reconstitution with a focus on both initial (day +21 BM, and +28 PB) and sustained engraftment (day +100 BM; PB at +14, +21, +28, +35, +42, +60, +100, +180, +1 and 2 years).
To determine the probability of overall survival and disease free survival at one and two years.
To describe the incidence of disease recurrence at one and two years in patients post UCBT.
To describe the incidence of acute GVHD and chronic GVHD at 100 days and at one year, respectively.
To determine the incidence of day 100 and 180 treatment related mortality.
To determine the incidence of serious infectious complications in the first year after transplant.
To determine the incidence of donor-derived neutrophil and platelet recovery.
To determine the incidence of secondary lymphoproliferative diseases following transplantation with umbilical cord blood.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive oral busulfan every 6 hours on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1.

TRANSPLANTATION: Patients undergo double-unit umbilical cord blood allogeneic stem cell transplantation on day 0.

GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally every 8 hours on days -3 to 45. After completion of study treatment, patients are followed periodically.

Enrollment

14 patients

Sex

All

Ages

12 to 64 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients will be diagnosed with one of the following hematological malignancies: acute myelogenous leukemia (AML), acute lymphoblastic leukemia, non-Hodgkin's lymphoma, myelodysplastic syndrome (MDS), chronic myelogenous leukemia (CML), and myeloproliferative and lymphoproliferative disorders
AML--First remission (CR1) with high risk features including a known prior diagnosis of myelodysplasia (MDS); therapy related AML; white cell count at presentation > 100,000; presence of extramedullary leukemia at diagnosis; unfavorable AML subtype (M0, M5-M7); poor cytogenetic markers (abnormalities of chromosome 5, 7 or 8, 11q23, Philadelphia chromosome, complex karyotype)
AML--Second remission (CR2) or subsequent remission
AML--Relapse/Persistent Disease with < 20% bone marrow blasts
ALL--First remission (CR1) at high risk for relapse as defined by: B cell ALL white blood cell count (WBC) at presentation > 30,000 (T cell ALL WBC > 100,000); presence of high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23), t(8;14)
ALL--Second remission (CR2) or subsequent remission
ALL--Relapse/Persistent Disease with < 20% bone marrow blasts
Non-Hodgkin Lymphoma--Induction failure or relapse and sensitive to most recent chemotherapy
MDS--Low or Intermediate-1 International Prognostic Scoring System (IPSS) score with: life-threatening cytopenia(s); and/or red cell or platelet transfusion dependence
MDS--ANC < 500, recurrent infections, PRBC transfusions > 2 units/month, poor risk cytogenetics, platelet transfusion dependence
MDS--Intermediate-2 or High IPSS score
CML--Chronic phase I (CP1) and resistant to or intolerant of tyrosine kinase inhibitors (i.e. imatinib, dasatinib, etc.)
CML--CP2 or subsequent chronic phase, including chronic phase achieved after induction therapy for blast crisis
Myeloproliferative and lymphoproliferative disorders--eligibility to be determined by a consensus of the physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee
Myeloproliferative and lymphoproliferative disorders--must have evidence of disease acceleration to be a candidate for umbilical cord blood transplant; myeloproliferative disorders eligible for transplant include chronic myelomonocytic leukemia (CMML) with high IPSS score and myelofibrosis
Myeloproliferative and lymphoproliferative disorders--potential lymphoproliferative disorders eligible for transplant include chronic lymphocytic leukemia, prolymphocytic leukemia, and large granular lymphocytic leukemia
Good performance status: Karnofsky >= 70 % or ECOG 0-1
Calculated creatinine clearance >= 60 mL/min, or measured creatinine clearance >= 60 mL/min (by 24-hour urine collection) if creatinine >= 1.5 or history of renal dysfunction
Hepatic Transaminases < 4 x upper limit normal (ULN); total bilirubin < 2.5 mg/dL, unless the patient has a history of benign congenital hyperbilirubinemia (Gilbert's syndrome)
Normal cardiac function by echocardiogram or radionuclide scan, (left ventricular ejection fraction > 45%); if the left ventricular ejection fraction is between 40-50%, clearance by an adult cardiologist is required
Pulmonary function tests demonstrating FEV1 > 60% of predicted for age
Adults must have a DLCOva > 60% normal
For patients unable to complete pulmonary function tests clearance by an adult pulmonologist is required
Patients will be eligible for the clinical trial under the following conditions: they do NOT have an HLA-A/B/DR B1 identical RELATED bone marrow donor; they do NOT have a 6/6 HLA-identical matched unrelated adult donor; OR a matched related donor transplant is not in the best interest of the patient (i.e., patient's condition precludes waiting on the donor, too much time to prepare the donor, the donor is ineligible due to medical reasons, or in the case of high risk disease a related donor is not appropriated (syngeneic transplant); the decision must be agreed upon by the consensus of physicians on the Case Comprehensive Cancer Center Leukemia/Lymphoma Multidisciplinary Committee; OR their condition precludes waiting to search and find a donor in the National Marrow Donor Registry

Exclusion criteria

Female patients who are pregnant or breast-feeding
HIV or HTLV-1 positivity
Any leukemia with a morphologic relapse or persistent disease in the BM with >= 20% blasts (cytogenetic relapse without morphologic evidence of relapse, or cytogenetic persistent disease is acceptable)
Active extramedullary leukemia, including CNS disease
Prior hematopoietic stem cell transplant (autologous or allogeneic)
Uncontrolled infection
Patient has an identical related bone marrow donor or a 6/6 HLA-identical matched unrelated donor
Any patient who is unable to provide informed consent or comply with the requirements of the protocol

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

14 participants in 1 patient group

Arm I

Experimental group

Description:

PREPARATIVE REGIMEN: Patients receive oral busulfan on days -8 to -5, cyclophosphamide IV on days -4 to -3, and anti-thymocyte globulin or methylprednisolone IV on days -3 to -1. TRANSPLANTATION: Patients undergo a double-unit umbilical cord blood allogeneic stem cell transplantation on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -2, patients receive cyclosporine IV and taper beginning on day 100. Patients also receive mycophenolate mofetil IV or orally on days -3 to 45.

Treatment: