Clinical trial NCT01093586: Donor Umbilical Cord Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official title: Umbilical Cord Blood (UCB) Allogeneic Stem Cell Transplant for Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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 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
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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2010-03-26
Enrollment: 14
Sex: ALL
Minimum age (years): 12
Maximum age (years): 64
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Overall Survival
timeFrame: On day +180
Secondary outcomes:
measure: Hematologic Engraftment
timeFrame: On day +42
measure: Overall Survival
timeFrame: At 1 year
measure: Overall Survival
timeFrame: At 2 years
measure: Disease Free
timeFrame: At 1 year
measure: Disease Free
timeFrame: At 2 years
measure: Recurrence or Relapse
timeFrame: one year in patients post UCBT
measure: Recurrence or Relapse
timeFrame: two years post transplant
measure: Transplant Related Mortality
timeFrame: On day 100 post transplant
measure: Transplant Related Mortality
timeFrame: On day 180 post transplant
measure: Occurrence of Serious Infections
timeFrame: 1 year
measure: Immune Reconstitution
timeFrame: Periodically for 2 years
measure: Toxicity Related to UCB Transplantation and Cytoreduction as Assessed by CTC v3.0
timeFrame: by day +42
measure: Incidence of Acute Graft-versus-host Disease (GVHD)
timeFrame: At 100 days
measure: Incidence of Chronic GVHD
timeFrame: At 1 year
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
name: Brenda Cooper, MD
role: PRINCIPAL_INVESTIGATOR
References: