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Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies


Phase 2
18 Years
65 Years
Not Enrolling
Both
Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

Transplantation of Two Partially Matched Umbilical Cord Blood Units Following Reduced Intensity Conditioning to Enhance Engraftment and Limit Transplant-Related Mortality in Adults With Hematologic Malignancies


OBJECTIVES:

Primary

- To evaluate the 100-day transplant-related (non-relapse) mortality in patients with
hematologic malignancies undergoing reduced-intensity conditioning comprising
fludarabine phosphate, melphalan, and anti-thymocyte globulin followed by sequential
umbilical cord blood transplantation (UCBT) from 2 partially-matched unrelated donors.

Secondary

- To evaluate the 12-month transplant-related (non-relapse) mortality.

- To evaluate the days to neutrophil engraftment (ANC > 500/mm³).

- To evaluate the days to platelet engraftment (platelet count > 20,000/mm³
[unsupported]).

- To evaluate the risk of acute and chronic graft-vs-host disease.

- To evaluate percent donor chimerism contribution of each cord unit.

- To evaluate relapse rate.

- To evaluate disease-free and overall survival.

- To evaluate transfusion support needed for UCBT recipients.

OUTLINE:

- Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days
-7 to -3, melphalan IV over 30-60 minutes on day -2, and anti-thymocyte globulin IV
over 4-6 hours on days -4 to -2.

- Transplantation: Patients undergo two sequential umbilical cord blood transplantations
on day 0.

- Graft-vs-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously
and then orally twice daily beginning on day -1 and continuing until day 60, followed
by a taper until day 180 in the absence of GVHD. Patients also receive mycophenolate
mofetil IV or orally twice daily beginning on day 0 and continuing until day 30,
followed by a taper until day 60 in the absence of GVHD.

After completion of study treatment, patients are followed periodically.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of hematologic malignancy for which a reduced-intensity allogeneic stem
cell transplantation is deemed clinically appropriate, including any of the
following:

- Chronic myelogenous leukemia, meeting one of the following criteria:

- In first chronic phase AND failed imatinib mesylate therapy, defined as
failure to obtain a hematologic remission by 3 months or major cytogenetic
response (Ph+ cells < 35%) by 12 months, or demonstrated clonal evolution
or disease progression while on therapy

- In accelerated phase with < 15% blasts

- In blast crisis that has entered into a second chronic phase following
induction chemotherapy

- Acute myelogenous leukemia, meeting one of the following criteria:

- In second or subsequent completion remission*

- Failed primary induction chemotherapy, but subsequently entered into a
complete remission* with ≤ 2 subsequent re-induction chemotherapy
treatment(s)

- In first complete remission* with poor-risk cytogenetics NOTE: *Complete
remission is defined as < 5% blasts in bone marrow, no definitive evidence
of disease by morphology, flow cytometry, or genetic studies, and no
circulating blasts. Neutrophil and platelet count recovery will not be
required.

- Acute lymphoblastic leukemia, meeting one of the following criteria:

- In second or subsequent complete remission

- In first complete remission AND t(9;22)

- Myelodysplastic syndromes, meeting the following criteria:

- High-risk disease, defined as International Prognostic Scoring System score
of ≥ 1.5

- Less than 10% blasts at the time of study enrollment

- Chronic myelomonocytic leukemia

- Less than 10% blasts at the time of study enrollment

- Myeloid metaplasia with myelofibrosis with poor-risk features, meeting one of
the following criteria:

- Age < 55 years AND a Lille score of 1

- Lille score of 2

- Hemoglobin < 10 g/dL AND abnormal karyotype

- Chronic lymphocytic leukemia/prolymphocytic leukemia, meeting all of the
following criteria:

- Rai stage I-IV disease

- Failed ≥ 1 prior chemotherapy regimen, including fludarabine, or autologous
stem cell transplantation

- Chemosensitive or stable, non-bulky disease prior to transplant

- Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and
involved-field radiotherapy are not considered prior regimens)

- Low-grade B-cell non-Hodgkin lymphoma (NHL) (small lymphocytic lymphoma,
follicular center [grade 1 or 2] lymphoma, or marginal zone lymphoma), meeting
all of the following criteria:

- Failed ≥ 1 prior chemotherapy regimen or autologous stem cell
transplantation

- Chemosensitive or stable, non-bulky disease prior to transplant

- Received ≤ 3 prior chemotherapy regimens (monoclonal antibody therapy and
involved-field radiotherapy are not considered prior regimens)

- Intermediate-grade B-cell or T-cell NHL or mantle cell NHL, meeting all of the
following criteria:

- Failed to achieve remission or recurred after either conventional
chemotherapy or autologous stem cell transplantation

- Chemosensitive, non-bulky disease prior to transplant

- Hodgkin lymphoma, meeting all of the following criteria:

- Relapsed after prior autologous stem cell transplantation or after ≥ 2
combination chemotherapy regimens AND ineligible for autologous peripheral
blood stem cell transplantation

- Chemosensitive, non-bulky disease prior to transplant

- Multiple myeloma, meeting one of the following criteria:

- Relapsed after autologous stem cell transplantation

- Relapsed after conventional therapies AND not a candidate for autologous
stem cell transplantation

- No HLA-matched related or unrelated donor available

- Has two umbilical cord blood units available that are matched at ≥ 4/6 HLA A, B, and
DRB1 with the patient and with each other (HLA C and DQ will not be used in the match
strategy)

- Total combined nucleated cell dose from the 2 umbilical cord blood units must be
> 3.7 x 10^7 nucleated cells/kg (pre-freeze dose) NOTE: A new classification
scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology
of "indolent" or "aggressive" lymphoma will replace the former terminology of
"low", "intermediate", or "high" grade lymphoma. However, this protocol uses the
former terminology.

PATIENT CHARACTERISTICS:

- Karnofsky performance status 80-100%

- Adapted, weighted Charlson Comorbidity Index < 3

- Serum creatinine ≤ 2.0 mg/dL

- AST or ALT < 3 times upper limit of normal (ULN)

- Bilirubin < 1.5 times ULN

- Not pregnant or nursing

- LVEF ≥ 40%

- DLCO > 50%

- No hypoxia at rest with oxygen saturation < 92% on room air (corrected with
bronchodilator therapy)

- No active opportunistic infection (e.g., fungal pneumonia, tuberculosis, or viral
infection)

- No active hepatitis B or C infection that, in the opinion of a gastroenterologist or
the transplant committee, places the patient at moderate- to high-risk for developing
severe hepatic disease

- No HIV infection

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Number of Participants With 100 Day Transplant-related Mortality (TRM)

Outcome Description:

100 Day TRM is death within 100 days from transplant related complications

Outcome Time Frame:

100 days

Safety Issue:

Yes

Principal Investigator

Scott R. Solomon, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Blood and Marrow Transplant Group of Georgia

Authority:

United States: Federal Government

Study ID:

CDR0000632453

NCT ID:

NCT00827099

Start Date:

June 2006

Completion Date:

November 2009

Related Keywords:

  • Myeloproliferative Disorders
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • accelerated phase cml
  • adult ALL in remission
  • adult AML in remission
  • adult AML with 11q23 (MLL) abnormalities
  • adult AML 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)
  • blastic phase chronic myelogenous leukemia
  • chronic myelomonocytic leukemia
  • chronic phase chronic myelogenous leukemia
  • prolymphocytic leukemia
  • recurrent adult T-cell leukemia/lymphoma
  • relapsing chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • refractory chronic lymphocytic leukemia
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • stage III chronic lymphocytic leukemia
  • stage IV chronic lymphocytic leukemia
  • recurrent adult Hodgkin lymphoma
  • anaplastic large cell lymphoma
  • angioimmunoblastic T-cell lymphoma
  • cutaneous B-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent mycosis fungoides/Sezary syndrome
  • adult grade III lymphomatoid granulomatosis
  • adult nasal type extranodal NK/T-cell lymphoma
  • Waldenstrom macroglobulinemia
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • nodal marginal zone B-cell lymphoma
  • splenic marginal zone 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 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
  • chronic idiopathic myelofibrosis
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • refractory multiple myeloma
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • Neoplasms
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders

Name

Location

Blood and Marrow Transplant Group of GeorgiaAtlanta, Georgia  30342-1601