Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Under 55	NCI	CASE-CWRU-4Y97 NCI-G98-1429, NCT00003335, CASE-4Y97

Objectives

1. 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.
2. Determine the incidence of graft-versus-host-disease in this setting.
3. Describe the incidence of recurrent disease in these patients post UCB transplant.
4. Describe the incidence of serious infections and secondary lymphoproliferative diseases following transplantation with UCB in these patients.
5. 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.

Entry 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

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

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/mm³
  • Absolute neutrophil count at least 1,000/mm³
  • Platelet count at least 100,000/mm³

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 FEV₁ 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

Expected Enrollment

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

Outcomes

Event-free survival by clinical and pathologic disease assessment at day 100, months 6, 9, and 12, and then yearly

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

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.

Lesniewski ML, Haviernik P, Weitzel RP, et al.: Regulation of IL-2 expression by transcription factor BACH2 in umbilical cord blood CD4+ T cells. Leukemia 22 (12): 2201-7, 2008.[PUBMED Abstract]

van Heeckeren WJ, Fanning LR, Meyerson HJ, et al.: Influence of human leucocyte antigen disparity and graft lymphocytes on allogeneic engraftment and survival after umbilical cord blood transplant in adults. Br J Haematol 139 (3): 464-74, 2007.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Mary Laughlin, MD, Protocol chair		Ph: 216-368-5693 Email: mjl13@po.cwru.edu

Registry Information
Official Title		A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With High Risk Hematologic Malignancies
Trial Start Date		1998-01-06
Trial Completion Date		2008-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00003335
Date Submitted to PDQ		1998-05-19
Information Last Verified		2009-03-18
NCI Grant/Contract Number		CA43703

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