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A Myeloablative Conditioning Regimen Consisting of Cyclophosphamide, Fludarabine and Total Body Irradiation Followed by the Transplantation of Unrelated Donor Double Unit Umbilical Cord Blood Grafts for Patients With Hematological Malignancy.


Phase 2
4 Years
50 Years
Open (Enrolling)
Both
Cancer, Leukemia, Myelodysplastic Syndrome, Non-Hodgkin's Lymphoma

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Trial Information

A Myeloablative Conditioning Regimen Consisting of Cyclophosphamide, Fludarabine and Total Body Irradiation Followed by the Transplantation of Unrelated Donor Double Unit Umbilical Cord Blood Grafts for Patients With Hematological Malignancy.


This is a single arm phase 2 study to obtain a preliminary estimate of efficacy of
myeloablative double unit umbilical cord blood transplantation (UCBT) as measured by overall
and disease-free survival at 1 year post transplantation. The UCB graft will consist of two
(or double) units from two unrelated newborn donors. Patients with hematopoietic malignancy
at high-risk for relapse or with advanced disease will receive myeloablative conditioning
with cyclophosphamide (Cy),low dose fludarabine (Flu) and total body irradiation (TBI) with
post transplantation cyclosporine (CSA) and mycophenolate mofetil (MMF) for GVHD
prophylaxis.


Inclusion Criteria:



- Age 4 - 50 years

- Patient should not have a related or unrelated volunteer donor that is suitably HLA
matched and available in the required time period or be a suitable candidate for an
autologous stem cell transplant.

- Patients will have one of the following hematological malignancies: Acute myelogenous
leukemia (AML):

- Complete first remission (CR1) at high risk for relapse as defined by:

known prior diagnosis of myelodysplasia (MDS); or therapy related AML; or White cell count
at presentation > 100,000; or Presence of extramedullary leukemia at diagnosis; or
Unfavorable FAB type (M0, M5-7); or High-risk cytogenetics (such as those associated with
MDS, abnormalities of 5, 7, 8, Philadelphia chromosome, complex karyotype); or High risk
molecular markers such as FLT3 mutations; or Requirement for 2 or more inductions to
achieve CR1

- Complete second CR (CR2).

• Acute lymphoblastic leukemia (ALL):

- Complete first remission (CR1) at high risk for relapse as defined by:

White cell count at presentation as follows:

- > 100,000 if < 18 years

- > 50,000 if > 18 years; or

Presence of extensive extra-medullary disease (excluding CNS disease); or Presence of
high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL
rearrangements (11q23), t(8;14) [excluding B-ALL in pediatric patients]; or

Failed to achieve complete remission after four weeks of induction therapy Unable to
receive required consolidation chemotherapy as would be needed to maintain remission

- Complete second or third remission (CR2 or CR3)

- Acute undifferentiated leukemia (AUL), infant leukemia, or biphenotypic leukemia
in CR1, CR2 or CR3. Patients with infant leukemia must be eligible to receive
total body irradiation.

- Juvenile Myelomonocytic leukemia (JMML) with < 30% bone marrow blasts.

- Chronic myelogenous leukemia (CML)

- GleevecTM failure in 1st or 2nd chronic phase;

- Gleevec failure in 1st or 2nd accelerated phase.

• Myelodysplastic Syndrome (MDS) with one of the following:

- Low (Score 0) International Prognostic Scoring System (IPSS) score with
Life-threatening cytopenia(s); or Red cell or platelet transfusion dependent

- Intermediate (Score 1) or High (Score 2) International Prognostic Scoring System
(IPSS) score.

- Patients with bone marrow blasts > 10% should have AML induction therapy with disease
response to < 5% blasts and at least partial count recovery.

• Non-Hodgkin's Lymphoma

- Patients with high-grade disease following initial therapy and are not appropriate
for further chemotherapy or autologous stem cell transplantation.

- Patients with high-grade or diffuse large cell NHL with recurrent disease after first
remission and must have:

Chemo-sensitivity as evidenced by > partial remission (PR) (defined as > 50% reduction in
mass size after therapy).

- Patients with adequate organ function and performance status criteria as measured by:

- Karnofsky score > or = to 70 % or Lansky score > or = to 70%

- Renal: Calculated creatinine clearance > or = to 60 ml/min

- Hepatic: Total bilirubin < 2.5 mg/dL unless benign congenital hyperbilirubinemia
(Gilbert's syndrome) and ALT/AST < 3 x upper limit of normal

- Albumin > or = to 2.5

- Pulmonary: Pulmonary function (spirometry and corrected DLCO) > or = to 60% normal if
available (in small children use History and Physical and CT scan as necessary to
determine pulmonary status)

- Cardiac: Left ventricular ejection fraction > or = to 50%

- Double Unit Umbilical Cord Blood Grafts:

Units will be selected based on the HLA match to the patient and on the basis of the
individual and combined cell doses of the units.

- Patient has a related or unrelated volunteer donor that is suitably HLA matched and
available in the required time period.

- Patient is a candidate for an autologous stem cell transplant.

- Active CNS leukemia.

- Acute Myelogenous Leukemia in greater than CR2.

- Acute Myelogenous Leukemia evolved from myelofibrosis.

- Acute Lymphoblastic Leukemia, acute undifferentiated leukemia, biphenotypic leukemia
or infant leukemia greater than CR3.

- Any acute leukemia with:

- Morphologic relapse or persistent disease in the BM (cytogenetic relapse without
morphologic evidence of relapse or cytogenetic persistent disease in the BM is
acceptable); or

- Active extra-medullary leukemia; or

- Requiring greater than 2 cycles of chemotherapy to obtain present remission
status;

- Bone Marrow aplasia (defined as BM cellularity less than 5% at transplant work-up);
or

- MDS with greater than 10% bone marrow blasts refractory to chemotherapy; or

- CML in blast crisis; or

- NHL refractory to chemotherapy (less than PR after 2 or more regimens); or

- Prior autologous or allogeneic HSC transplant at any time; or

- Prior radiation therapy rendering patient ineligible for TBI; or

- Uncontrolled viral, bacteria or fungal infection at time of study enrollment; or

- Seropositive or NAT positive for HIV; or

- Females who are pregnant or breast feeding; or

- Patient or guardian unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, follow-up, and research
tests.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To obtain a preliminary estimate of efficacy of double unit UCBT as measured by overall and disease-free survival at 1 year.

Outcome Time Frame:

1 year

Safety Issue:

Yes

Principal Investigator

Juliet Barker, MBBS

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

06-014

NCT ID:

NCT00597519

Start Date:

March 2006

Completion Date:

March 2014

Related Keywords:

  • Cancer
  • Leukemia
  • Myelodysplastic Syndrome
  • Non-Hodgkin's Lymphoma
  • Cancer
  • Leukemia
  • Myelodysplastic Syndrome
  • Non-Hodgkin's Lymphoma
  • Total Body Irradiation
  • Umbilical Cord Blood Grafts
  • 06-014
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021