Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer

Lymphoma Clinical Trial

Official title:

A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003335
• Other study ID #: CWRU4Y97
• Secondary ID: P30CA043703NCI-G
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: March 14, 2012
• Start date: January 1998
• Est. completion date: January 2012

Study information

• Verified date: March 2012
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying allogeneic umbilical cord blood transplantation to see how well it works when given with chemotherapy or radiation therapy in treating patients with high-risk hematologic cancer.

Description:

OBJECTIVES:

• Determine the rates of hematologic and immune reconstitution in patients with high risk hematologic malignancies who are undergoing high dose chemoradiotherapy followed by unrelated umbilical cord blood (UCB) transplantation.

• Determine the incidence of graft-versus-host-disease in this setting.

• Describe the incidence of recurrent disease in these patients post UCB transplant.

• Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.

• Determine specifically whether larger recipients can be durably engrafted with unrelated UCB, and determine whether nucleated cell or progenitor cell content of the graft is predictive of hematological engraftment.

OUTLINE: Patients may undergo a back-up peripheral blood stem cell collection prior to treatment.

Patients receive 9 fractions of total body irradiation (TBI) on days -9 to -5 followed by melphalan IV for three days on days -4 to -2 and antithymocyte globulin IV or methylprednisolone IV for three days on days -3 to -1. On day 0, patients receive umbilical cord blood infusion. If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5. Cyclosporine and methylprednisolone begin on day -2 and continue for 6 months.

Patients are followed at least monthly for 1 year, then every 6 months for the second year, and then annually thereafter.

PROJECTED ACCRUAL: There will be a maximum of 48 patients accrued into this study over 4 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: January 2012
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 54 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed high risk malignancy including:

• Acute nonlymphocytic leukemia (ANLL) after induction failure, or in first complete remission with high risk features including stem cell or biphenotypic classification (acute myeloid leukemia (AML) M0), erythroleukemia (AML M6), acute megakaryocytic leukemia (AML M7), cytogenic markers indicative of poor prognosis, or failure to achieve complete remission after standard induction therapy

• Acute lymphocytic leukemia (ALL) or ANLL in second or subsequent remission

• Chronic myeloid leukemia (CML) in chronic phase

• CML with accelerated phase or blast crisis are eligible after reinduction chemotherapy converts disease to chronic phase

• High risk ALL in first complete remission

• Myelodysplastic syndrome with evidence of evolution to acute myeloid leukemia

• Refractory anemia with excess blasts

• Refractory anemia with excess blasts in transformation

• Non-Hodgkin's lymphoma (NHL), ANLL, or ALL with recurrent disease after autologous stem cell transplantation

• Must also meet all the following conditions:

• No HLA-ABC/DR identical related bone marrow or UCB donor

• No 5/6 antigen matched related bone marrow or UCB donor

• Condition precludes waiting to search and find a donor in the National Marrow Donor Registry

• Must have an available serologic matched umbilical cord blood unit in the New York Blood Center's Placental Blood Project

• No active CNS disease

PATIENT CHARACTERISTICS:

Age:

• Under 55 at time of umbilical cord blood transplantation

Performance status:

• Zubrod 0-1

• Karnofsky 80-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• For patients with ALL or ANLL in remission, CML in chronic phase, or NHL without marrow involvement who elect to undergo autologous peripheral blood stem cell collection and storage:

• WBC at least 3,000/mm^3

• Absolute neutrophil count at least 1,000/mm^3

• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

• ALT/AST no greater than 4 times normal

Renal:

• Creatinine no greater than 2.0 mg/dL

• Creatinine clearance at least 50 mL/min

Cardiovascular:

• Normal cardiac function by echocardiogram or radionuclide scan (shortening fraction or ejection fraction at least 80% of normal value for age)

Pulmonary:

• FVC and FEV_1 at least 60% of predicted for age

• For adults:

• DLCO at least 60% of predicted

Other:

• HIV negative

• No active infections at time of autologous stem cell harvest or pretransplant cytoreduction

• Not pregnant or nursing

• Effective contraception required of all fertile patients

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior autologous stem cell transplantation allowed

Chemotherapy:

• See Disease Characteristics

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin
antithymocyte globulin IV for three days on days -3 to -1

Drug:
• busulfan
If TBI is not tolerated, busulfan is substituted and administered orally every 6 hours for 4 days on days -8 to -5.
• cyclosporine
Cyclosporine begin on day -2 and continue for 6 months.
• melphalan
melphalan IV for three days on days -4 to -2
• methylprednisolone
Methylprednisolone IV for three days on days -3 to -1. Methylprednisolone begin on day -2 and continue for 6 months.

Procedure:
• umbilical cord blood transplantation
On day 0, patients receive umbilical cord blood infusion.

Radiation:
• radiation therapy
9 fractions of total body irradiation (TBI) on days -9 to -5

Locations

Country	Name	City	State
United States	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Lesniewski ML, Haviernik P, Weitzel RP, Kadereit S, Kozik MM, Fanning LR, Yang YC, Hegerfeldt Y, Finney MR, Ratajczak MZ, Greco N, Paul P, Maciejewski J, Laughlin MJ. Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ — View Citation

van Heeckeren WJ, Fanning LR, Meyerson HJ, Fu P, Lazarus HM, Cooper BW, Tse WW, Kindwall-Keller TL, Jaroscak J, Finney MR, Fox RM, Solchaga L, Forster M, Creger RJ, Laughlin MJ. Influence of human leucocyte antigen disparity and graft lymphocytes on allog — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	rates of durable engraftment in patients	The primary study end point will be hematologic engraftment. Engraftment is defined as achieving ANC larger than or equal to 500 ul/mm3 of donor origin for three consecutive measurements on different days by day +42.	day 42	No
Secondary	Event-free survival by clinical and pathological disease assessment		at disease progression or death	No
Secondary	incidence of recurrent disease in patients post UCB transplant		post transplant	No