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

NCT ID: NCT01093586

Last Updated: 2019-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2015-12-31

Brief Summary

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.

Detailed Description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

1. 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.

2. 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).

3. To determine the probability of overall survival and disease free survival at one and two years.

4. To describe the incidence of disease recurrence at one and two years in patients post UCBT.

5. To describe the incidence of acute GVHD and chronic GVHD at 100 days and at one year, respectively.

6. To determine the incidence of day 100 and 180 treatment related mortality.

7. To determine the incidence of serious infectious complications in the first year after transplant.

8. To determine the incidence of donor-derived neutrophil and platelet recovery.

9. 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.

Conditions

Recurrent Childhood Lymphoblastic Lymphoma; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Juvenile Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; 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 Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell 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; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Splenic Marginal Zone Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; Waldenstrom Macroglobulinemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

double-unit umbilical cord blood transplantation

Intervention Type: PROCEDURE

Undergo transplantation

cytogenetic analysis

Intervention Type: OTHER

Correlative studies

bone marrow aspiration

Intervention Type: PROCEDURE

Correlative studies

fluorescence in situ hybridization

Intervention Type: OTHER

Correlative studies

busulfan

Intervention Type: DRUG

Given orally

cyclophosphamide

Intervention Type: DRUG

Given IV

anti-thymocyte globulin

Intervention Type: DRUG

Given IV

methylprednisolone

Intervention Type: DRUG

Given IV

cyclosporine

Intervention Type: DRUG

Given IV

mycophenolate mofetil

Intervention Type: DRUG

Given orally or IV

flow cytometry

Intervention Type: OTHER

Correlative studies

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo transplantation

Interventions

double-unit umbilical cord blood transplantation

Undergo transplantation

Intervention Type: PROCEDURE

cytogenetic analysis

Correlative studies

Intervention Type: OTHER

bone marrow aspiration

Correlative studies

Intervention Type: PROCEDURE

fluorescence in situ hybridization

Correlative studies

Intervention Type: OTHER

busulfan

Given orally

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

anti-thymocyte globulin

Given IV

Intervention Type: DRUG

methylprednisolone

Given IV

Intervention Type: DRUG

cyclosporine

Given IV

Intervention Type: DRUG

mycophenolate mofetil

Given orally or IV

Intervention Type: DRUG

flow cytometry

Correlative studies

Intervention Type: OTHER

allogeneic hematopoietic stem cell transplantation

Undergo transplantation

Intervention Type: PROCEDURE

Other Intervention Names

fluorescence in situ hybridization (FISH); BSF; BU; Misulfan; Mitosan; Myeloleukon; Myelosan; CPM; CTX; Cytoxan; Endoxan; Endoxana; Enduxan; ATG; ATGAM; lymphocyte immune globulin; Thymoglobulin; A-MethaPred; Depo-Medrol; Medrol; MePRDL; Solu-Medrol; Wyacort; 27-400; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Cellcept; MMF

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 64 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Case Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Brenda Cooper, MD

Role: PRINCIPAL_INVESTIGATOR

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Locations

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

Other Identifiers

NCI-2009-01319

Identifier Type: OTHER

Identifier Source: secondary_id

CASE3Z07

Identifier Type: OTHER

Identifier Source: secondary_id

CASE3Z07

Identifier Type: -

Identifier Source: org_study_id