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Antineoplastic Agents

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Cyclophosphamide

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Fludarabine phosphate

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CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients undergo a lower dose of TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Allogeneic Hematopoietic Stem Cell Transplantation

Fludarabine Phosphate

Laboratory Biomarker Analysis

Mycophenolate Mofetil

Total-Body Irradiation

Umbilical Cord Blood Transplantation

Rachel Salit

This phase II trial is studying how well umbilical cord blood transplant from a donor works in treating patients with hematological cancer. Giving chemotherapy and total-body irradiation (TBI) before a donor umbilical cord blood transplant 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 healthy 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 (called graft-versus-host disease). Giving cyclosporine and mycophenolate mofetil before and after transplant may stop this from happening.

PRIMARY OBJECTIVES:

I. Estimate probability of one year survival.

II. Demonstrate equivalent or improved engraftment rates with a non-anti-thymocyte globulin (ATG) based conditioning regimen. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below:

* Absence of 3 consecutive days with neutrophils \>= 500/ul combined with host cluster of differentiation (CD)3 peripheral blood chimerism \>= 50% at day 42
* Absence of 3 consecutive days with neutrophils \>= 500/ul under any circumstances at day 55
* Death after day 28 with neutrophil count \< 100/ul without any evidence of engraftment (\< 5% donor CD3)
* Primary autologous count recovery with \< 5% donor CD3 peripheral blood chimerism at count recovery and without relapse

SECONDARY OBJECTIVES:

I. Six month non-relapse mortality.

II. Overall incidence of graft failure/rejection. Patients will be considered graft failure/rejections provided they meet any of the criteria listed below:

* Absence of 3 consecutive days with neutrophils \>= 500/ul combined with host CD3 peripheral blood chimerism \>= 50% at day 42
* Absence of 3 consecutive days with neutrophils \>= 500/ul under any circumstances at day 55
* Death after day 28 with neutrophil count \< 100/ul without any evidence of engraftment (\< 5% donor CD3)
* Primary autologous count recovery with \< 5% donor CD3 peripheral blood chimerism at count recovery and without relapse

III. Kinetics of chimeric reconstitution.

IV. Incidence of neutrophil engraftment by day 42.

V. Incidence of platelet engraftment by six months.

VI. Incidence of grade II-IV and III-IV acute graft-versus-host disease (GvHD) at day 100.

VII. Incidence of one year chronic GvHD.

VIII. Incidence of clinically significant infections at 6 months, 1 year, 2 years.

IX. Probability of one and two year survival.

X. Incidence of one and two year relapse or disease progression.

XI. Fred Hutchinson Cancer Research Center (FHCRC) patients: Kinetics of immune reconstitution, with both functional and quantitative assays.

XII. FHCRC patients: Examination of possible immunologic factors leading to emergence of a dominant unit.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients undergo a lower dose of total-body irradiation (TBI) on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days -3 to +180 and mycophenolate mofetil IV or orally (PO) every 8 hours on days 0 to +96.

After completion of study treatment, patients are followed periodically for up to 2 years.

Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

Transplantation of Umbilical Cord Blood in Patients With Hematological Malignancies Using a Reduced-Intensity Preparative Regimen (A Multi-Center Trial Coordinated by the FHCRC)

Kaplan-Meier and cumulative incidence estimates will be used.

Chi-square test was used to determine percent of grade II-IV GVHD using Glucksberg criteria

Fischer's exact test was used to determined percent of patients with acute grade III-IV GVHD by Glucksberg criteria

Kaplan-Meier and cumulative incidence estimates will be used to measure percent of patients with chronic GVHD by NIH consensus criteria.

Kaplan-Meier and cumulative incidence estimates

National Cancer Institute (NCI)

Fred Hutchinson Cancer Center

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6.

Patients with low risk of graft failure receive 200 cGy TBI on day -1.

Patients with high risk of graft failure receive 300 cGy TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Treatment (Chemotherapy, Transplant)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6.

ARM 1(patients at low risk for graft failure) - patients receive 200cGy TBI ARM 2 (patients at high risk for graft failure) - patients receive 300cGy TBI

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo single or double umbilical cord blood transplant

Patients \> 70 may be considered if performance status \> 80% or Eastern Cooperative Oncology Group (ECOG) =\< 1 and comorbidity score \< 3; these patients must be discussed with the principal investigator (PI), Rachel Salit prior to enrollment

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Scale from 0-100 with

100= Normal no complaints 90= Normal activity with minor signs or symptoms of disease 80= Normal activity with effort, some signs or symptoms of disease 70= Cares for self, unable to carry on normal activity 60= Requires occasional assistance 50= Requires considerable assistance 40= Disabled 30= Severely disabled 20= Very sick, hospitalized 10= Moribund 0= Dead

Karnofsky Performance Scale

The HCT-CI is a comorbidity index that comprises 17 different categories of organ dysfunction. Positive findings are summated into a total score. The HCT-CI provides information with regard to the overall as well as non-relapse mortality risk a patient is likely to experience after hematopoietic cell transplantation. Lower scores have been shown to be associated with lower non relapse mortality.

Hematopoeitic Cell Transplant Comorbidity Index

Cytomegalovirus Status

Disease

Remission Status

Only patients in a complete remission were assessed for minimal residual disease. All others are known to have residual disease

Minimal Residual Disease

Number of cord blood donors

The standard for selecting unrelated umbilical cord blood units for transplantation for non-malignant diseases relies on antigen-level (lower resolution) HLA typing for HLA-A and HLA-B, and allele-level for HLA-DRB1. A 6 of 6 cord blood in matched at A, B and DR on both Haplotypes. 5 of 6 has one mismatch and 4 of 6 has 2 mismatched. 4 of 6 is commonly the maximum number of mismatches accepted for a cord blood transplant.

Level of HLA matching

Patients were given 200 or 300 cGy TBI based on set definitions of high risk or low risk of graft failure. This was NOT a randomized study designed to show which dose of TBI was more effective.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients with low risk of graft failure (multi-agent chemotherapy in the last 3 months or history of autologous transplant) receive 200cGy TBI on day -1. Patients with high risk of graft failure receive 300 cGy TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo umbilical cord blood transplant

Overall Survival

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6. Patients with low risk of graft failure (multi-agent chemotherapy in the last 3 months or history of autologous transplant) receive 200cGy TBI on day -1. Patients with high risk of graft failure receive 300 cGy TBI on day -1.

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Allogeneic Hematopoietic Stem Cell Transplantation: Undergo umbilical cord blood transplant

Fludarabine Phosphate: Given IV

Laboratory Biomarker Analysis: Correlative studies

Mycophenolate Mofetil: Given IV or PO

Total-Body Irradiation: Undergo TBI

Umbilical Cord Blood Transplantation: Undergo umbilical cord blood transplant

Median Time to ANC > 500

Number of Participants With Graft Failure/Rejection

Time to Platelet Engraftment of > 20,000 Cells Per mm3

Percent of Patients With Grade II-IV Acute Graft Versus Host Disease

Percent of Patients With Acute GVHD Grades III-IV

Percent of Patients With Chronic GVHD

Percent of Patients With Non-relapse Mortality

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 1 hour on days -6 to -2 and cyclophosphamide IV over 1-2 hours on day -6.

Arm 1 (patients with lower risk of graft failure-have received multi-agent chemotherapy in the prior 2 months or history of prior autologous transplant): Patients undergo 200 cGy TBI on day -1.

Arm 2 (patients at higher risk of graft failure-have not received multi agent chemotherapy in the prior 2 months and no history of prior autologous transplant): Patients undergo 300 cGy TBI on day -1

UMBILICAL CORD BLOOD TRANSPLANT: Patients undergo donor umbilical cord blood infusion on day 0.

IMMUNOSUPRESSIVE THERAPIES: Patients receive cyclosporine IV over 1 hour every 8-12 hours on days 0 to +180 and mycophenolate mofetil IV or PO every 8 hours on days -3 to +96.

Arm 1 and 2 Treatment

Overall Study

Spots Global Cancer Trial Database for refractory chronic myelogenous leukemia