Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00304018

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and etoposide, before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor 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 tacrolimus and prednisone after transplant may stop this from happening.

PURPOSE: This phase I trial is studying how well donor umbilical cord blood transplant works in treating patients with advanced hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes	Biological: anti-thymocyte globulin Biological: sargramostim Drug: busulfan Drug: etoposide Drug: fludarabine phosphate Drug: prednisone Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation	Phase 1

Detailed Description

OBJECTIVES:

Primary

Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of > 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

Secondary

Determine the toxicity of a myeloablative preparative regimen comprising busulfan, fludarabine, and etoposide prior to UCBT in these patients.
Determine the neutrophil and platelet recovery in patients treated with this regimen.
Determine the event-free and overall survival of patients treated with this regimen.
Evaluate lineage-specific chimerism after UCBT and assess the contribution of each individual cord blood unit to post-transplantation hematopoiesis in these patients.
Determine the incidence, severity, and timing of acute and chronic graft-vs-host disease in patients treated with this regimen.

OUTLINE: This is a pilot study.

Preparative regimen: Patients receive fludarabine IV over 30 minutes on days -7 to -3, busulfan IV over 2 hours 4 times daily on days -7 and -4, etoposide IV over 4 hours on day -3, and anti-thymocyte globulin IV over 6 hours on days -2 and -1.
Donor umbilical cord blood transplantation (UCBT): Patients undergo donor UCBT on day 0. Beginning on day 7, patients receive sargramostim (GM-CSF) IV or subcutaneously once daily until blood counts recover.
Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously over 24 hours or orally twice daily beginning on day -2 and continuing until day 180 followed by a taper. Patients also receive oral prednisone twice daily on days 13-50 and then once daily on days 50-60, followed by a rapid taper.

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

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Umbilical Cord Blood Transplantation in Adult Patients With Advanced Hematopoietic Malignancies

Study Start Date :

Oct 1, 2002

Actual Primary Completion Date :

Mar 1, 2009

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: cord blood transplant	Biological: anti-thymocyte globulin Biological: sargramostim Drug: busulfan Drug: etoposide Drug: fludarabine phosphate Drug: prednisone Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation

Arm

Intervention/Treatment

Experimental: cord blood transplant

Biological: anti-thymocyte globulin

Biological: sargramostim

Drug: busulfan

Drug: etoposide

Drug: fludarabine phosphate

Drug: prednisone

Drug: tacrolimus

Procedure: allogeneic hematopoietic stem cell transplantation

Procedure: umbilical cord blood transplantation

Outcome Measures

Primary Outcome Measures

Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies [up to 24 months post-transplant]
Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies, in terms of > 80% engraftment rate at day 100 post-transplant and ≤ 50% transplant-related mortality.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following advanced hematologic malignancies:
Acute myeloid leukemia (AML) meeting the following criteria:
Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:
High-risk cytogenetics (-7, -7q, -5, -5q, t[6,9], t[9,11], complex, Philadelphia chromosome positive [Ph+])
AML evolved from prior myelodysplasia
AML secondary to prior chemotherapy
Failed to achieve remission
In second or subsequent remission
Marrow blasts ≤ 10% (may be achieved using chemotherapy)
Myelodysplastic syndromes (MDS) with high-risk features
International Prognostic Scoring System (IPSS) score intermediate -2 or high-risk
Marrow blasts ≤ 20% (may be achieved using chemotherapy)
Acute lymphoblastic leukemia meeting the following criteria:
Not expected to be curable with chemotherapy and meets ≥ 1 of the following criteria:
High-risk cytogenetics (Ph+, t[4,11], 11q23 abnormalities, and monosomy

Required > 1 induction course to achieve remission
Failed to achieve remission
In second or subsequent remission
Marrow blasts ≤ 10% (may be achieved using chemotherapy)
Chronic myelogenous leukemia meeting ≥ 1 of the following criteria:
Accelerated phase
Chronic phase refractory to imatinib mesylate
Blastic phase
Marrow blasts ≤ 10% (may be achieved using chemotherapy)
Multiple myeloma meeting 1 of the following criteria:
Stage II or III disease with > first relapse or refractory disease
Newly diagnosed disease with chromosome 13 abnormalities
Lymphoma meeting the following criteria:
One of the following subtypes:
Diffuse large cell lymphoma
Mantle cell lymphoma
Peripheral T-cell lymphoma
T-natural killer (NK) cell lymphoma
Hodgkin's lymphoma
Disease failed to respond to primary therapy, progressed, or recurred after prior therapy
Patients who have failed autologous stem cell transplantation are eligible provided it has been > 1 year since transplant
No rapid progression of malignant disease
Not eligible for autologous stem cell transplantation
Available umbilical cord blood (1-3 units) donor matching at ≥ 4 of 6 HLA antigens (A, B, and DR)
Patients with an HLA-identical or 1 antigen-mismatched related donor OR a potential HLA-matched unrelated donor matching at > 6/8 (A, B, C, DR) alleles are not eligible

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Creatinine < 2.0 mg/dL
Creatinine clearance > 40 mL/min
Bilirubin < 2.0 mg/dL
AST and alkaline phosphatase < 3 times upper limit of normal
Hepatitis C and active hepatitis B allowed if patient has ≤ grade 2 inflammation or fibrosis by liver biopsy
Ejection fraction > 40% by echocardiogram or MUGA
DLCO > 40% of predicted
Not pregnant or nursing
Negative pregnancy test
No known HIV infection
No active infection requiring ongoing antibiotic treatment