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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00304018
• Other study ID #: CDR0000463370
• Secondary ID: UCSF-02253UCSF-H
• Status: Completed
• Phase: Phase 1
• First received: March 15, 2006
• Last updated: August 13, 2013
• Start date: October 2002
• Est. completion date: March 2009

Study information

• Verified date: August 2013
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Multiple Myeloma
• Multiple Myeloma and Plasma Cell Neoplasm
• Myelodysplastic Syndromes
• Neoplasms, Plasma Cell
• Plasmacytoma
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin

• sargramostim

Drug:
• busulfan

• etoposide

• fludarabine phosphate

• prednisone

• tacrolimus

Procedure:
• allogeneic hematopoietic stem cell transplantation

• umbilical cord blood transplantation

Locations

Country	Name	City	State
United States	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the safety and feasibility of performing donor umbilical cord blood transplantation (UCBT) in patients with advanced hematologic malignancies	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.	up to 24 months post-transplant	Yes