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

• ClinicalTrials.gov Identifier: NCT00003335
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Last Update Posted: March 15, 2012
• Sponsor: Case Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Case Comprehensive Cancer Center

Tracking Information

• First Submitted Date: November 1, 1999
• First Posted Date: January 27, 2003
• Last Update Posted Date: March 15, 2012
• Study Start Date: January 1998
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 7, 2011)

rates of durable engraftment in patients [ Time Frame: day 42 ]

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.

• Original Primary Outcome Measures: Not Provided

Current Secondary Outcome Measures (submitted: December 7, 2011)

• Event-free survival by clinical and pathological disease assessment [ Time Frame: at disease progression or death ]
• incidence of recurrent disease in patients post UCB transplant [ Time Frame: post transplant ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Umbilical Cord Blood Transplantation in Treating Patients With High-Risk Hematologic Cancer
• Official Title: A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies

Brief 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.

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Graft Versus Host Disease
• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myelodysplastic/Myeloproliferative Diseases

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.
• Drug: cyclosporine
  Cyclosporine begin on day -2 and continue for 6 months.
• Drug: melphalan
  melphalan IV for three days on days -4 to -2
• Drug: 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

• Study Arms: Not Provided

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. doi: 10.1038/leu.2008.234. 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.
• Kindwall-Keller TL, Hegerfeldt Y, Meyerson HJ, Margevicius S, Fu P, van Heeckeren W, Lazarus HM, Cooper BW, Gerson SL, Barr P, Tse WW, Curtis C, Fanning LR, Creger RJ, Carlson-Barko JM, Laughlin MJ. Prospective study of one- vs two-unit umbilical cord blood transplantation following reduced intensity conditioning in adults with hematological malignancies. Bone Marrow Transplant. 2012 Jul;47(7):924-33. doi: 10.1038/bmt.2011.195. Epub 2011 Oct 17.
• 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. doi: 10.1182/blood-2008-09-181156. Epub 2009 Mar 13.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 7, 2011): 44
• Original Enrollment: Not Provided
• Actual Study Completion Date: January 2012
• Actual Primary Completion Date: November 2007 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 54 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00003335
• Other Study ID Numbers: CWRU4Y97; P30CA043703 ( U.S. NIH Grant/Contract ); NCI-G98-1429; CWRU4Y97 ( Other Identifier: Case Comprehensive Cancer Center )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Case Comprehensive Cancer Center
• Study Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

• Study Chair: Brenda W. Cooper, MD; Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

• PRS Account: Case Comprehensive Cancer Center
• Verification Date: March 2012