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Allogeneic Stem Cell Transplantation for Patients With Hematological Malignancies Using Multiple Unrelated Cord Blood Units


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Open (Enrolling)
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Leukemia, Lymphoma, Myelodysplastic Syndromes

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Trial Information

Allogeneic Stem Cell Transplantation for Patients With Hematological Malignancies Using Multiple Unrelated Cord Blood Units


OBJECTIVES:

Primary

- To determine the survival at day 100 of patients with relapsed, refractory, or
poor-risk hematological malignancies treated with four different preparative regimens
followed by allogeneic hematopoietic stem cell transplantation (HSCT) using two
unrelated umbilical cord blood (UCB) units.

Secondary

- To determine the incidence and timing of neutrophil engraftment in patients treated
with these regimens.

- To determine the incidence and timing of platelet engraftment in patients treated with
these regimens.

- To determine the incidence and severity of acute and chronic graft-versus-host-disease
(GVHD) in patients treated with these regimens.

- To determine the survival at day 180 in patients treated with these regimens.

- To determine the disease-free survival in patients treated with these regimens.

- To determine the incidence of primary and secondary engraftment failure in patients
treated with these regimens.

- To determine the incidence of transplantation-related complications (e.g., infection,
veno-occlusive disease of the liver, or organ toxicity) in these patients.

- To determine the incidence of post-transplantation-related lymphoproliferative disease,
secondary myelodysplastic syndromes, or other secondary malignancies in these patients.

- To determine the incidence of relapse in patients treated with these regimens.

- To determine post-transplantation chimerism in patients treated with these regimens.

- To determine immune reconstitution in patients treated with these regimens.

OUTLINE: This is a multicenter study.

- Preparative regimens: Patients are assigned to 1 of 4 preparative regimens.

- Regimen 1 (for patients < 50 years of age and no contraindication to fractionated
total-body irradiation (FTBI): Patients undergo FTBI 2-3 times a day on days -9 to
-6 for a total of 11 fractions. Patients also receive cyclophosphamide IV over 2
hours on days -5 and -4 and fludarabine phosphate IV on days -5 to -2.

- Regimen 2 (for patients < 50 years of age and unable to tolerate FTBI due to prior
dose-limiting radiotherapy or significant cardiotoxicity): Patients receive a test
dose of busulfan on day -10 and then dose adjusted busulfan IV 3-4 times daily on
days -9 to -6, melphalan IV on days -5 and -4, and fludarabine phosphate IV on
days -5 to -2.

- Regimen 3* (for patients unable to tolerate regimen 1 or 2; no age exclusion):
Patients receive fludarabine phosphate IV on days -8 to -4 and cyclophosphamide IV
over 2 hours on day -3 and undergo TBI (single dose) on day -2.

- Regimen 4* (for patients unable to tolerate regimen 1 or 2): Patients receive
fludarabine phosphate IV on days -7 to -3 and melphalan IV on day -2.

NOTE: *Treating physician decides the choice between regimen 3 and 4

- Umbilical cord blood (UCB) transplantation: Patients receive 2 combined units of UCB IV
on day 0. Patients also receive G-CSF IV or subcutaneously beginning on day 5 (or
later) and continuing until blood counts recover.

- Graft-versus-host-disease prophylaxis: Patients receive cyclosporine IV twice daily
beginning on day -1 followed by a taper according to institutional guidelines. Patients
also receive mycophenolate mofetil orally or IV beginning on day 0 and continuing until
day 27 (or as clinically indicated).

After completion of study therapy, patients are followed periodically.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed hematological or lymphatic malignancy, including any of the
following:

- Acute myeloid leukemia

- Relapsed or primary refractory disease with < 10% blasts on peripheral
blood smear

- In first remission with poor risk factors and molecular prognosis [i.e.,
AML with -5, -7, t(6;9), tri8, -11] (preparative regimen 3 or 4)

- Acute lymphocytic leukemia

- In second complete remission or higher OR in first remission with poor risk
factors, including any of the following (preparative regimen 1 or 2):

- BCR/ABL by fluorescence in situ hybridization (FISH) or reverse
transcriptase-polymerase chain reaction

- t(9;22)(q34;q11) detected by cytogenetics

- Chromosomes < 44 by cytogenetics

- DNA index < 0.81 by flow cytometry

- Any rearrangement of chromosome 11 that results in disruption of MLL
gene (11q23) by cytogenetics and SER

- In first remission with poor risk factors and molecular prognosis [ALL with
Philadelphia chromosome-positive t(9;22), t(4;22), (q34;q11)] (preparative
regimen 3 or 4)

- Chronic myelogenous leukemia

- In accelerated phase or greater (preparative regimen 1 or 2)

- In accelerated or second chronic phase (preparative regimen 3 or 4)

- Myelodysplastic syndromes

- With deletion of chromosome 7 or short arm of chromosome 5 (preparative
regimen 1 or 2)

- In high and high-intermediate risk categories (preparative regimen 3 or 4)

- Non-Hodgkin lymphoma in relapse with marrow involvement

- Refractory chronic lymphocytic leukemia

- Patients deemed ineligible for conventional high-dose chemotherapy programs (i.e.,
regimens 1 or 2) due to any of the following concurrent medical conditions may be
eligible for regimens 3 or 4 at the discretion of the treating physician and
principal investigator (preparative regimen 3 or 4):

- LVEF < 50% and > 40%

- FEV1, FVC, or DLCO < 50%

- Bilirubin > 3 mg/dL

- Creatinine > 2 mg/dL

- Two partially HLA-matched umbilical cord blood (UCB) units available

- HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and -DRB1 loci with the patient

- DRB1 matched by high resolution DNA typing

- HLA-A and HLA-B matched by low resolution at the "serological match" level

- Two pooled units with a nucleated cell number > 2.5 x 10^7/kg

- No available HLA-identical sibling or 1 antigen-mismatched related donor

- No available HLA-matched unrelated bone marrow donor

PATIENT CHARACTERISTICS:

- See Disease Characteristics

- Karnofsky performance status (PS) 60-100% OR Lansky PS 60-100% OR Zubrod PS 0-1

- Physiological age 60 or less (at any chronological age)

- Weight > 50 kg

- Creatinine normal for age OR creatinine clearance by 24-hour urine collection or
glomerular filtration rate > 60 mL/min

- Bilirubin ≤ 1.5 mg/dL

- LVEF ≥ 50%

- DLCO ≥ 60% of predicted

- No HIV-1 infection

- No active uncontrolled infection

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

- Recovered from prior intensive chemotherapy

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Survival at day 100 after allogeneic hematopoietic stem cell transplantation (HSCT) from umbilical cord blood (UCB)

Outcome Time Frame:

Day 100

Safety Issue:

No

Principal Investigator

Joseph Rosenthal, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute

Authority:

United States: Institutional Review Board

Study ID:

02165

NCT ID:

NCT00547196

Start Date:

August 2003

Completion Date:

Related Keywords:

  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • refractory chronic lymphocytic leukemia
  • adult acute myeloid leukemia in remission
  • recurrent adult acute myeloid leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • adult acute lymphoblastic leukemia in remission
  • accelerated phase chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • recurrent adult Burkitt lymphoma
  • recurrent adult diffuse large cell lymphoma
  • recurrent adult diffuse mixed cell lymphoma
  • recurrent adult diffuse small cleaved cell lymphoma
  • recurrent adult grade III lymphomatoid granulomatosis
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent adult lymphoblastic lymphoma
  • recurrent grade 1 follicular lymphoma
  • recurrent grade 2 follicular lymphoma
  • recurrent grade 3 follicular lymphoma
  • recurrent mantle cell lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone lymphoma
  • relapsing chronic myelogenous leukemia
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • secondary acute myeloid leukemia
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

City of Hope Comprehensive Cancer CenterDuarte, California  91010
Banner Good Samaritan Medical CenterPhoenix, Arizona  85006