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Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients Wtih Advanced Hematopoietic Malignancies

18 Years
70 Years
Not Enrolling
Acute Myeloid Leukemia, Myelodysplasia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Multiple Myeloma, Lymphomas, Low-grade NHL and Chronic Lymphocytic Leukemia

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Trial Information

Pilot Study of Reduced-Intensity Umbilical Cord Blood Transplantation in Adult Patients Wtih Advanced Hematopoietic Malignancies

Primary Objective:

- To assess the feasibility of performing umbilical cord blood transplants in older
adults or younger infirm patients using a reduced-intensity preparative regimen.
Feasibility of the procedure is defined as an engraftment rate of >80% at Day 180
post-transplantation and a transplant related mortality (TRM) of <50% at Day 100. A TRM
of >50% will be considered unacceptable.

Secondary objectives:

- To describe the time to neutrophil and platelet recovery following mini-UCB

- To assess lineage-specific chimerism following transplantation and to describe the
contribution of each individual CB unit to post-transplantation hematopoeisis.

- To describe disease-specific, event-free and overall survival rates at 180 and 360

- To describe the incidence, severity, and timing of acute and chronic GVHD following
reduced-intensity UCB transplantation.

- To evaluate T-cell, B-cell, and NK cell recovery following reduced-intensity UCB

Inclusion Criteria:

- Age 55-70 years, or < 55 years if deemed ineligible for conventional high dose
chemotherapy by the UCSF SCT Committee or by protocol eligibility requirements for
myeloablative therapy. Reasons for ineligibility for myeloablative therapy include:

- Poor cardiac function (i.e. LVEF < 40%)

- Poor pulmonary function (i.e. DLCO < 50%)

- Hepatic dysfunction

- Prior myeloablative therapy

- Availability of donor cord blood (one to three units) matching at > or equal to 4 of
6 HLA antigens (A, B, and DR). HLA class I antigens will be determined by serologic
methods, and Class II antigens will be determined by high-resolution DNA typing.
Typing will be confirmed by the UCSF Immunogenetics Department. The target UCB TNC
dose is > or equal to 3.5 x 10(7) TNC/kg recipient weight, however the absolute
minimum TNC requirement is > 2.5 x 10(7) TNC per kilogram) based on cell counts prior
to cryopreservation. Cord blood units will be obtained from all available
international banks.

- HLA identical or 1 antigen mismatched related donors or potential HLA-matched
unrelated donors (MUD) must NOT be readily available

- Disease types include:

- Acute myeloid leukemia not expected to be curable with chemotherapy. This will
include patients with high-risk cytogenetics (-7, -7q, -5, -5q, t(6, 9), t(9,
11), complex (> or equal to 3 abnormalities), Ph(+), evolution from prior
myelodysplasia or AML secondary to prior chemotherapy, failure to achieve
remission, second, or subsequent remission or refractory relapse. Marrow blasts
must be < or equal to 10%. This may be achieved using standard chemotherapy

- Myelodysplasia with high-risk features. This will include patients with IPSS
category INT2 or HI-risk MDS or CMML. Marrow blasts must be < or equal to 20%.
If required, chemotherapy may be given to achieve target levels of blasts.
Patients are expected to have disease control or not rapidly progressive disease
regardless of blast count (but must be < or equal to 20%).

- Acute lymphoblastic leukemia not expected to be cured with chemotherapy. This
will include patients with high-risk cytogenetics (Ph+, t(4,11), 11q23
abnormalities, and monosomy 7), patients requiring more than one induction
course to achieve remission, as well as patients failing to enter remission or
in second or subsequent remission. Marrow blasts must be < or equal to 10%. If
required, chemotherapy may be given to achieve target level of blasts.

- Chronic myelogenous leukemia- chronic phase failing imatinib mesylate therapy
(either progressive disease or failure to achieve a major cytogenetic response
at 1 year following initiation of therapy), accelerated phase failing to achieve
a complete cytogenetic remission at 1 year following initiation of therapy,
accelerated phase failing to achieve any cytogenetic response at 6 months of
therapy, accelerated phase with progressive disease as demonstrated by worsening
cytogenetic response in two consecutive analyses separated by 4 weeks or CML in
blast crisis. Patients with blast phase of CML must have < 10% blasts in bone

- Multiple myeloma stage I-III with relapse following autologous transplant, with
disease refractory to at least two prior conventional; myeloma therapies or with
chromosome 13 abnormalities. Patients with chromosome 13 abnormalities are
eligible either at diagnosis or after initial progression.

- Lymphomas including diffuse or follicular large cell lymphoma, mantle cell
lymphoma, peripheral T-cell lymphoma, T-NK cell lymphoma, or Hodgkin's disease
which has failed to respond to primary therapy, progressed, or recurred after
prior therapy. Patients who have relapsed following autologous transplant are

- Low-grade NHL and Chronic Lymphocytic Leukemia with relapse or refractory
disease following, at least, two chemotherapy-based treatment regimens; or with
relapse following autologous transplantation.

- Patients must have an ECOG PS < or equal to 2.

- Laboratory requirements:

- Creatinine < 2.0mg/dL and creatinine clearance > 40/m/min (calculated or based
on 24-hour urine collection)

- Bilirubin <2.0mg/dL, AST/alkphos <3x upper limit of normal

- Patients with hepatitis C and active hepatitis B (hepatitis B DNA detectable)
are eligible only if a liver biopsy is performed and there is grade < or equal
to 2 fibrosis and/or inflammation. Patients with a history of HBV infection
should be tested for HBeAg, anti-HBe and HBV DNA (quantitative). Patients with
active HBV viral replication should receive anti-viral therapy.

- Cardiac ejection fraction > 30%, DLCO > or equal to 40%.

- Negative pregnancy test (for females of reproductive age only).

- Signed informed consent

Exclusion Criteria:

- Active infection requiring ongoing antibiotic treatment

- HIV infection

- Poor performance status (ECOG > 2)

- Opinion of BMT Committee that autologous SCT or conventional therapy would be a
preferable form of treatment

- Organ function is below requirements

- Pregnancy, or breast-feeding

Type of Study:


Study Design:

Observational Model: Case-Only, Time Perspective: Prospective

Principal Investigator

Thomas G. Martin, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of California, San Francisco


United States: Institutional Review Board

Study ID:




Start Date:

August 2004

Completion Date:

June 2009

Related Keywords:

  • Acute Myeloid Leukemia
  • Myelodysplasia
  • Acute Lymphoblastic Leukemia
  • Chronic Myelogenous Leukemia
  • Multiple Myeloma
  • Lymphomas
  • Low-grade NHL and Chronic Lymphocytic Leukemia
  • Umbilical cord blood transplantation
  • hematopoietic malignancies
  • Neoplasms
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms



University of California San FranciscoSan Francisco, California  941104206