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

NCT01093586 | Completed Phase 2 Results DMC

• 2 other identifiers: CASE3Z07NCI-2009-01319
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Number of participants alive at 180 days post engraftment.

  On day +180

Secondary Outcomes (14)

• Hematologic Engraftment

  On day +42

• Overall Survival

  At 1 year

• Overall Survival

  At 2 years

• Disease Free

  At 1 year

• Disease Free

  At 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Procedure: double-unit umbilical cord blood transplantation; Other: cytogenetic analysis; Procedure: bone marrow aspiration; Other: fluorescence in situ hybridization; Drug: busulfan; Drug: cyclophosphamide; Drug: anti-thymocyte globulin; Drug: methylprednisolone; Drug: cyclosporine; Drug: mycophenolate mofetil; Other: flow cytometry; Procedure: allogeneic hematopoietic stem cell transplantation

Interventions

double-unit umbilical cord blood transplantation PROCEDURE

Undergo transplantation

Arm I

cytogenetic analysis OTHER

Correlative studies

Arm I

bone marrow aspiration PROCEDURE

Correlative studies

Arm I

fluorescence in situ hybridization OTHER

Correlative studies

Also known as: fluorescence in situ hybridization (FISH)

Arm I

busulfan DRUG

Given orally

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon, Myelosan

Arm I

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana, Enduxan

Arm I

anti-thymocyte globulin DRUG

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Arm I

methylprednisolone DRUG

Given IV

Also known as: A-MethaPred, Depo-Medrol, Medrol, MePRDL, Solu-Medrol, Wyacort

Arm I

cyclosporine DRUG

Given IV

Also known as: 27-400, ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Arm I

mycophenolate mofetil DRUG

Given orally or IV

Also known as: Cellcept, MMF

Arm I

flow cytometry OTHER

Correlative studies

Arm I

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo transplantation

Arm I

Eligibility Criteria

• Age: 12 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

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

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Congenital Abnormalities; Leukemia, Erythroblastic, Acute; Lymphoma, Extranodal NK-T-Cell; Blast Crisis; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Leukemia, Myelomonocytic, Chronic; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myelomonocytic, Juvenile; Myeloproliferative Disorders; Lymphoma, B-Cell, Marginal Zone; Leukemia, Prolymphocytic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Large-Cell, Anaplastic; Dendritic Cell Sarcoma, Interdigitating; Lymphoma, T-Cell, Cutaneous; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Mycosis Fungoides; Sezary Syndrome; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Large Granular Lymphocytic; Waldenstrom Macroglobulinemia

Interventions

Cytogenetic Analysis; In Situ Hybridization, Fluorescence; Busulfan; Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate; Cyclosporine; Cyclosporins; Mycophenolic Acid; Flow Cytometry

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Bone Marrow Diseases; Lymphoma, T-Cell; Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Lymphoid; Histiocytic Disorders, Malignant; Histiocytosis; Leukemia, B-Cell; Leukemia, T-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; In Situ Hybridization; Staining and Labeling; Histocytological Preparation Techniques; Histological Techniques; Nucleic Acid Hybridization; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Peptides, Cyclic; Macrocyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Brenda Cooper MD
• Organization: Case Comprehensive Cancer Center

brenda.cooper@uhhospitals.org

216-844-3213

Study Officials

• Brenda Cooper, MD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2010
• First Posted: March 26, 2010
• Study Start: September 1, 2007
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 23, 2019
• Results First Posted: January 4, 2019

Record last verified: 2019-01

Locations

US (1)