Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematological Cancer or Other Disease

NCT00719849 | Terminated Phase 2 Results

• 4 other identifiers: 2012.00FHCRC-2012.00CDR0000597623T32CA009515
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Giving low doses of chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer or abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well donor umbilical cord blood transplant with reduced intensity conditioning works in treating patients with advanced hematological cancer or other disease.

Conditions

Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Keywords

chronic myelogenous leukemia; acute lymphoblastic leukemia; acute myeloid leukemia; atypical chronic myeloid leukemia; chronic myelomonocytic leukemia; anaplastic large cell lymphoma; splenic marginal zone lymphoma; nodal marginal zone B-cell lymphoma; recurrent adult Hodgkin lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent childhood large cell lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; recurrent/refractory childhood Hodgkin lymphoma; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; refractory multiple myeloma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; myelodysplastic/myeloproliferative disease; childhood myelodysplastic syndromes; recurrent childhood anaplastic large cell lymphoma; refractory anemia; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage III childhood anaplastic large cell lymphoma; stage III childhood large cell lymphoma; stage IV childhood anaplastic large cell lymphoma; stage IV childhood large cell lymphoma; stage III adult Hodgkin lymphoma; stage III childhood Hodgkin lymphoma; stage IV adult Hodgkin lymphoma; stage IV childhood Hodgkin lymphoma; stage II multiple myeloma; stage III multiple myeloma; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III small lymphocytic lymphoma; stage IV small lymphocytic lymphoma; stage III marginal zone lymphoma; stage IV marginal zone lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; Waldenstrom macroglobulinemia; stage III mantle cell lymphoma; stage IV mantle cell lymphoma; stage III mycosis fungoides/Sezary syndrome; stage IV mycosis fungoides/Sezary syndrome; juvenile myelomonocytic leukemia; chronic eosinophilic leukemia; chronic idiopathic myelofibrosis; chronic neutrophilic leukemia; essential thrombocythemia; polycythemia vera

Outcome Measures

Primary Outcomes (1)

• Probability of Survival at 1 Year

  Kaplan-Meier estimate of the probability of survival at 1 year

  1 year post transplant

Secondary Outcomes (15)

• Probability of Survival at 2 Years

  2 years post transplant

• Incidence of Non-relapse Mortality at 6 Months

  6 months post transplant

• Chimerism

  7 days, 14 days, 21 days, 28 days, 56 days, and 80 days, 6 months, 1 and 2 years post transplant

• Incidence of Neutrophil Engraftment at Day 42

  Day 42 post transplant

• Incidence of Platelet Engraftment at 6 Months

  6 months post transplant

Study Arms (2)

Cyclophosphamide/Fludarabine/TBI

EXPERIMENTAL

Subjects with hematological malignancies with prior autologous transplant, \>2 cycles of multiagent chemotherapy, or severely immune suppressive therapy in last 3 months. Refractory leukemia and lymphoma in aplasia after induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy.

Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: umbilical cord blood transplantation; Radiation: total body irradiation

Cyclophosphamide/Fludarabine/TBI/ATG

EXPERIMENTAL

Subjects with hematological malignancies with prior autologous transplant \>12 mos or \<1 cycle of multiagent chemotherapy or NO immune suppressive chemotherapy in last 3 months

Biological: anti-thymocyte globulin; Drug: cyclophosphamide; Drug: cyclosporine; Drug: fludarabine phosphate; Drug: mycophenolate mofetil; Procedure: umbilical cord blood transplantation; Radiation: total body irradiation

Interventions

anti-thymocyte globulin BIOLOGICAL

30mg/Kg Days -6 to -4

Cyclophosphamide/Fludarabine/TBI/ATG

cyclophosphamide DRUG

50 mg/Kg Day -6

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

cyclosporine DRUG

Patients will receive cyclosporine A (CSA) therapy beginning on Day -3 maintaining a trough level between 250 and 500 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

fludarabine phosphate DRUG

40mg/m2 Days -6 to -2

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

mycophenolate mofetil DRUG

1 gram every 8 hours for patients who are ≥ 40 kg. Pediatric patients (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours. Stop MMF at Day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD.

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

umbilical cord blood transplantation PROCEDURE

Single or double unit umbilical cord blood transplant

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

total body irradiation RADIATION

200 cGy Day -1

Cyclophosphamide/Fludarabine/TBI; Cyclophosphamide/Fludarabine/TBI/ATG

Eligibility Criteria

• Age: Up to 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of advanced hematologic malignancy or other disease not curable by conventional chemotherapy, including any of the following: * Acute myeloid leukemia in complete remission (CR)\* (as defined by hematologic recovery, \< 5% blasts in the bone marrow by morphology, and a cellularity of \> 15%), meeting one of the following criteria: * In first complete remission (CR1) AND has high-risk disease as evidenced by any of the following: * Preceding myelodysplastic syndromes (MDS) * High-risk cytogenetics (e.g., monosomy 5 or 7, or as defined by referring institution treatment protocol) * Required \> 2 courses of therapy to obtain CR * Erythroblastic or megakaryocytic leukemia * In second CR (CR2) or beyond * Acute lymphoblastic leukemia in CR\* (as defined by hematologic recovery, \< 5% blasts in the bone marrow by morphology, and a cellularity of \> 15%), meeting one of the following criteria: * In CR1 AND has high-risk disease as evidenced by any of the following: * t(9;22), t(1;19), t(4;11), or other MLL rearrangements * Hyplodiploid * Required \> 1 course of therapy to obtain CR * Beyond CR2 * Chronic myelogenous leukemia (CML) * All types are allowed (except refractory blast crisis CML) * Patients in chronic phase CML must have failed or been intolerant to prior imatinib mesylate (Gleevec) or other tyrosine kinase inhibitors * MDS * Any subtype allowed (including refractory anemia \[RA\]) * Severe pancytopenia or complex cytogenetics * Blasts must be \< 5% (if blasts are ≥ 5%, pre-transplant induction therapy is required to reduce blast count to \< 5%) * Large cell lymphoma, Hodgkin lymphoma, or multiple myeloma, meeting one of the following criteria: * Chemotherapy-sensitive disease that has failed prior therapy * Patients with large cell lymphoma or Hodgkin lymphoma must not have progressive disease during salvage therapy (stable disease allowed provided it is non-bulky) * Ineligible for an autologous stem cell transplant * Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, or follicular lymphoma that has progressed after ≥ 2 prior therapies * Patients with bulky disease should be considered for debulking chemotherapy prior to transplant * Patients with refractory disease are eligible provided disease is non-bulky AND an estimated tumor doubling time is ≥ 1 month * Lymphoplasmacytic lymphoma, mantle cell lymphoma, or prolymphocytic leukemia * Chemotherapy-sensitive disease that was previously treated with initial therapy * Patients with mantle cell lymphoma must not have progressive disease during salvage therapy (stable disease allowed provided it is non-bulky) * Mycosis fungoides and Sezary syndrome * Bone marrow failure syndromes, except for Fanconi anemia * Myeloproliferative syndromes NOTE: \*Patients for whom adequate marrow/biopsy specimens can not be obtained to determine remission status by morphologic assessment must have fulfilled criteria of remission (\< 5% blasts by flow cytometry and recovery of peripheral blood counts with no circulating blasts) * Ineligible for autologous stem cell transplant due to any of the following: * Prior autologous stem cell transplant * Inadequate autologous stem cell harvest * Inability to withstand a myeloablative preparative regimen * Clinically aggressive/high-risk disease * No evidence of progressive disease by imaging modalities or biopsy (persistent PET scan activity allowed provided there are no CT scan changes indicating progression) * Acute leukemia that is refractory, persistent, or relapsed (defined as \> 5% blasts in normocellular bone marrow) allowed provided patient was rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy * Patients with stable disease are eligible provided the largest residual nodal mass is approximately \< 5 cm (largest residual mass must represent a 50% reduction and be approximately \< 7.5 cm for patients who have responded to prior therapy) * No active CNS malignancy * Umbilical cord blood (UCB) donor available * UCB graft matched at 4/6 HLA-A, -B, and -DRB1 antigens with the recipient * May include 0-2 antigen mismatches at the A, B, or DRB1 loci * Unit selection based on cryopreserved nucleated cell dose and HLA-A, -B, and -DRB1 using intermediate resolution A, B antigen and DRB1 allele typing * If 2 UCB units are required to reach the target cell dose, each unit must be a 3/6 HLA-A, -B, and -DRB1 antigen match to each other, as well as a 4/6 antigen match to the recipient * No 5-6/6 HLA-A, -B, and -DRB1 matched sibling donor available PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) 60-100% OR Lansky PS 50-100% * Creatinine ≤ 2.0 mg/dL (adults) OR creatinine clearance \> 40 mL/min (pediatrics) * Adult patients with a creatinine \> 1.2 mg/dL or a history of renal dysfunction must have an estimated creatinine clearance of \> 40 mL/min * Not pregnant or nursing * Negative pregnancy test * LVEF ≥ 35% * DLCO \> 30% predicted * No requirement for O\_2 * No decompensated congestive heart failure * No uncontrolled arrhythmia * None of the following liver diseases or conditions: * Fulminant liver failure * Cirrhosis with evidence of portal hypertension or bridging fibrosis * Alcoholic hepatitis * Esophageal varices * History of bleeding esophageal varices, hepatic encephalopathy, or correctable hepatic synthetic dysfunction as evidenced by prolongation of the prothrombin time * Ascites related to portal hypertension * Bacterial or fungal abscess * Biliary obstruction * Chronic viral hepatitis with total serum bilirubin \> 3 mg/dL * Symptomatic biliary disease * Recent mold infection (e.g., Aspergillus) allowed provided patient received ≥ 30 days of appropriate treatment AND infection is controlled and cleared by Infectious Disease * No evidence of HIV infection or known HIV-positive serology * No uncontrolled viral or bacterial infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics * At least 3 months since prior myeloablative stem cell transplantation

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Lymphoma, Large-Cell, Anaplastic; Lymphoma, B-Cell, Marginal Zone; Hodgkin Disease; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Dendritic Cell Sarcoma, Interdigitating; Mycosis Fungoides; Sezary Syndrome; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Recurrence; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Waldenstrom Macroglobulinemia; Leukemia, Myelomonocytic, Juvenile; Pdgfra-Associated Chronic Eosinophilic Leukemia; Primary Myelofibrosis; Leukemia, Neutrophilic, Chronic; Thrombocythemia, Essential; Polycythemia Vera

Interventions

Antilymphocyte Serum; Cyclophosphamide; Cyclosporine; fludarabine phosphate; Mycophenolic Acid; Cord Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Bone Marrow Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Lymphoid; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Histiocytic Disorders, Malignant; Histiocytosis; Lymphoma, T-Cell, Cutaneous; Leukemia, B-Cell; Anemia; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. Colleen Delaney
• Organization: Fred Hutchinson Cancer Research Center

cdelaney@fredhutch.org

2066671385

Study Officials

• Colleen Delaney, MD, MSC

  Fred Hutchinson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 19, 2008
• First Posted: July 22, 2008
• Study Start: November 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: December 1, 2009
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

US (1)