Donor Umbilical Cord Blood Transplant in Treating Patients With Advanced Hematologic Cancer
Status and phase
Conditions
Treatments
Study type
Funder types
Identifiers
Details and patient eligibility
About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
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 7)
- 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
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Trial design
Primary purpose
Allocation
Interventional model
Masking
5 participants in 1 patient group
Trial contacts and locations
Loading...
Data sourced from clinicaltrials.gov
Clinical trials
Research sites
Resources
Legal