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

Sponsor:	Case Comprehensive Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00003335

Purpose

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.

Condition	Intervention	Phase
Graft Versus Host Disease Leukemia Lymphoma Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclosporine Drug: melphalan Drug: methylprednisolone Procedure: umbilical cord blood transplantation Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma

Drug Information available for: Busulfan Cyclosporine Cyclosporin Methylprednisolone Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Event-free survival by clinical and pathologic disease assessment at day 100, months 6, 9, and 12, and then yearly [ Designated as safety issue: No ]

Secondary Outcome Measures:

Rates of umbilical cord blood donor engraftment by chimerism (time of myeloid recovery) at days 60 and 100 and months 6, 9, 12, 18, and 24 [ Designated as safety issue: No ]

Estimated Enrollment:	48
Study Start Date:	January 1998
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

Ages Eligible for Study:	up to 54 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003335

Locations

United States, Ohio
Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators

Case Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Mary J. Laughlin, MD

Case Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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+ T cells. Leukemia. 2008 Dec;22(12):2201-7. Epub 2008 Sep 4.

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 allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol. 2007 Nov;139(3):464-74.

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Weitzel RP, Lesniewski ML, Haviernik P, Kadereit S, Leahy P, Greco NJ, Laughlin MJ. microRNA 184 regulates expression of NFAT1 in umbilical cord blood CD4+ T cells. Blood. 2009 Jun 25;113(26):6648-57. Epub 2009 Mar 13.

Responsible Party:	Case Comprehensive Cancer Center ( Mary J. Laughlin )
Study ID Numbers:	CDR0000066304, CASE-CWRU-4Y97, NCI-G98-1429, CASE-4Y97
Study First Received:	November 1, 1999
Last Updated:	March 19, 2009
ClinicalTrials.gov Identifier:	NCT00003335 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

recurrent childhood acute lymphoblastic leukemia
recurrent childhood lymphoblastic lymphoma
recurrent adult acute lymphoblastic leukemia
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
untreated childhood acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood acute lymphoblastic leukemia in remission
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)

refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
graft versus host disease

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Cyclosporine
Molecular Mechanisms of Pharmacological Action
Methylprednisolone
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Cyclosporins
Preleukemia
Pathologic Processes
Therapeutic Uses
Dermatologic Agents
Methylprednisolone Hemisuccinate

Immunoproliferative Disorders
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Myeloproliferative Disorders
Glucocorticoids
Neoplasms
Melphalan
Precancerous Conditions
Immunologic Factors
Antineoplastic Agents
Prednisolone acetate
Neuroprotective Agents
Leukemia
Syndrome

ClinicalTrials.gov processed this record on November 09, 2009