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The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-versus-Host Prophylaxis With Tacrolimus and Mycophenolate Mofetil


N/A
N/A
50 Years
Not Enrolling
Both
Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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Trial Information

The Treatment of Hematologic Malignancies With Single or Double Umbilical Cord Blood Unit Transplantation Followed by Graft-versus-Host Prophylaxis With Tacrolimus and Mycophenolate Mofetil


OBJECTIVES:

Primary

- To determine the safety (as assessed by the day 100 non-relapse mortality) and
feasibility of single or double umbilical cord stem cell transplantation in patients
with hematological malignancies receiving graft-versus-host disease (GVHD) prophylaxis
comprising tacrolimus and mycophenolate mofetil (MMF).

Secondary

- To assess sustained donor engraftment, neutrophil recovery, platelet recovery,
incidence and severity of acute graft-versus-host disease (GVHD) and chronic GVHD,
relapse rate, 100-day all-cause mortality, overall survival, and immune reconstitution
after single or double umbilical cord stem cell transplantation in patients with
hematologic malignancies receiving graft-versus-host disease(GVHD) prophylaxis
comprising tacrolimus and mycophenolate mofetil (MMF).

OUTLINE:

- Conditioning: Patients receive myeloablative or reduced-intensity conditioning regimen
according to age and prior treatment.

- Myeloablative conditioning (pediatric patients): Patients undergo total-body
irradiation on days -7 to -4, and receive cyclophosphamide IV over 1 hour on days
-3 and -2, methylprednisolone IV twice daily on days -3 to -1, and anti-thymocyte
globulin IV over 4 hours on days -3 to -1.

- Myeloablative conditioning (adult patients 18-40 years old): Patients receive
fludarabine phosphate IV over 30 minutes on days -6 to -4, cyclophosphamide IV
over 1 hour on days -5 and -4, and undergo total-body irradiation on days -3 to
-1.

- Reduced-intensity conditioning (patients over 40 and no more than 50 years old OR
deemed ineligible for above myeloablative conditioning regimen due to previous
treatment): Patients receive fludarabine phosphate IV over 30 minutes on days -6
to -2 and cyclophosphamide IV over 1 hour on day -6 and undergo total-body
irradiation on day -1.

- Umbilical cord blood transplantation (UCBT): All patients undergo single- or
double-unit umbilical cord blood transplantation (UCBT)on day 0.

- Graft-versus-host disease prophylaxis: Patients receive tacrolimus IV continuously or
orally twice daily on days -2 to 180 followed by a tapering and mycophenolate mofetil
IV or orally twice daily on days 0-100 followed by a tapering over the next 3 months.
Patients also receive filgrastim (G-CSF) IV or subcutaneously beginning on day 0* and
continuing until blood counts recover.

NOTE: *In adult patients receiving a reduced intensity transplant, G-CSF will be started
when the total white cell count falls below 2.5 x 109/L.

After completion of study treatment, patients are followed monthly for 1 year and then every
2-4 months thereafter.


Patient and UCB Unit Selection:

Inclusion Criteria:

General (Adults and Pediatrics)

Only one of the following should be present:

- Acute leukemia (lymphocytic or myeloid or undifferentiated or biphenotypic) in
complete remission 2 or beyond

- Acute lymphocytic leukemia, Philadelphia chromosome positive in complete remission 1
or beyond

- Acute myeloid leukemia in complete remission 1 if it has evolved from a
myeloproliferative disorder (MPD) or myelodysplastic syndrome (MDS).

- Acute leukemia in complete remission 1 if there is a failure to recover normal blood
counts or the development of MDS following induction chemotherapy.

- Therapy related acute leukemia in complete remission 1 or beyond

- Chronic myeloid leukemia (CML) chronic phase-1 (imatinib failures, imatinib
intolerance), or any CML beyond first chronic phase

- Myelodysplastic syndromes (Intermediate -1 or higher risk by IPSS)

- Therapy related MDS (irrespective of IPSS)

- Multiple myeloma must have had prior chemotherapy or autologous transplant

- Chronic lymphocytic leukemia must have failed two lines of conventional therapy but
still chemosensitive to third line therapy.

- Chemosensitive Non-Hodgkin's lymphoma or Hodgkin's lymphoma in CR or PR after failing
induction therapy.

- High risk acute leukemia/lymphoma eg Nk/T cell, HTLV associated leukemia/lymphoma,
other T cell lymphoma/leukemia in first best response

- For patients with acute leukemia-they must be in a remission (less than 5% leukemic
marrow blasts) at time of study entry.

Inclusion Criteria (Adults - 18 years or older)

- Karnofsky score of > 70%

- Estimated creatinine clearance of > 60 ml/min

- Left ventricular ejection fraction of >50%

- Pulmonary function test with DLCO, FEV1 and FVC of >60%

- Total bilirubin and SGOT of < 3.0 x upper limits of normal

- Note: Age 18- 40 years for adult myeloablative conditioning Age > 40 -50 years for
adult reduced intensity conditioning

Inclusion Criteria (Pediatrics - 18 years and younger)

- Karnofsky or Lansky score of > 70%

- Estimated Creatinine clearance of > 60 ml/min

- Left ventricular ejection fraction of >50%

- Pulmonary function test with FEV1 and FVC of >60% (for patients >6 years of age)

- Total bilirubin and SGOT of < 3.0 x upper limits of normal

- Note: All pediatric patients will receive myeloablative conditioning

Inclusion Criteria - Donor Issues

- No available HLA identical or 1 antigen/allele mismatched (Class I-A, B or Class II
DR locus) related donor

Inclusion Criteria:

Umbilical Cord Blood Unit-HLA Typing

- At least a HLA 4/6 match (Class I-A, B by low resolution, Class II-DR by high
resolution) to recipient

- For double UCB SCT each unit should be at least a 4/6 match (Class I-A,B by low
resolution, Class II-DR by high resolution) to recipient, and should be at least a
4/6 match (Class I-A,B by low resolution, Class II-DR by high resolution) to each
other

Inclusion Criteria:

Umbilical Cord Blood Unit-Cell dose

- For Single UCB SCT: the unit will have ≥ 3.5 X 107 NC/kg of recipient body weight
(For pediatric patients a cell dose ≥ 3.0 X 107 NC/kg of recipient body weight is
acceptable). Recipient body weight will be determined as per standard guidelines.

- For Double UCB SCT: (done only if no single UCB unit ≥ 3.5 X 107 NC/kg of recipient
body weight is available for adults, and ≥ 3.0 X 107 NC/kg of recipient body weight
is available for pediatric patients )

- The larger of the two units (UCB1) will have a minimum cell dose of 2.0 X 107 NC/kg
of recipient body weight. The smaller of the two units (UCB2) will have a minimum of
0.5 X 107 NC/kg of recipient body weight.

The total cell dose UCB1 + UCB2 will be ≥ 2.5 X 107 NC/kg of recipient body weight.

-Adult patients eligible for a double UCB SCT but without an appropriate second UCB unit
will be enrolled in the study if their single UCB unit contains ≥ 2.5 x 107 NC/kg
recipient body weight.

Exclusion Criteria

- Organ dysfunction as per standard guidelines. Unable to give informed consent (for
adults only)

- Pregnant or lactating

- Sexually active individuals capable of becoming pregnant or causing a pregnancy who
are unable or unwilling to use appropriate contraceptives.

- Active use of illicit drugs as evidenced by a positive toxicology screen for a
substance not prescribed by a medical professional just prior to initiating the
preparative regimen

- Actively smoking as evidenced by a positive nicotine screen just prior to initiating
the preparative regimen

- HIV positive

- Patients with other unrelated malignancies will be excluded except:

- diagnosis of skin cancer (squamous cell or basal cell)

- diagnosis of cervical dysplasia (CIN I-III)

- any other malignancy which is currently in remission and was treated with curative
intent more than 5 years preceding study entry

- In patients with secondary MDS or secondary acute leukemias-the previous
non-hematopoietic neoplasm should be in remission but can be within 5 years of study
entry

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Number of Participants With 100-day Non-relapse Mortality

Outcome Description:

Evaluate the safety (as determined by the day 100 non-relapse mortality) and feasibility of single or double umbilical cord blood (UCB)stem cell transplant (SCT) in adult or pediatric patients with hematologic malignancies receiving graft-versus-host disease (GVHD) prophylaxis with tacrolimus and mycophenolate mofetil (MMF).

Outcome Time Frame:

100 days

Safety Issue:

Yes

Principal Investigator

Brian Engelhardt, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

VICC BMT 0552

NCT ID:

NCT00608517

Start Date:

September 2005

Completion Date:

May 2011

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Lymphoma
  • Multiple Myeloma and Plasma Cell Neoplasm
  • Myelodysplastic Syndromes
  • graft versus host disease
  • accelerated phase chronic myelogenous leukemia
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • 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)
  • blastic phase chronic myelogenous leukemia
  • childhood acute lymphoblastic leukemia in remission
  • childhood acute myeloid leukemia in remission
  • childhood chronic myelogenous leukemia
  • chronic phase chronic myelogenous leukemia
  • de novo myelodysplastic syndromes
  • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • nodal marginal zone B-cell lymphoma
  • noncontiguous stage II adult Burkitt lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse mixed cell lymphoma
  • noncontiguous stage II adult diffuse small cleaved cell lymphoma
  • noncontiguous stage II adult immunoblastic large cell lymphoma
  • noncontiguous stage II adult lymphoblastic lymphoma
  • noncontiguous stage II adult non-Hodgkin lymphoma
  • noncontiguous stage II grade 1 follicular lymphoma
  • noncontiguous stage II grade 2 follicular lymphoma
  • noncontiguous stage II grade 3 follicular lymphoma
  • noncontiguous stage II mantle cell lymphoma
  • noncontiguous stage II marginal zone lymphoma
  • noncontiguous stage II small lymphocytic lymphoma
  • previously treated myelodysplastic syndromes
  • secondary acute myeloid leukemia
  • secondary myelodysplastic syndromes
  • splenic marginal zone lymphoma
  • stage I multiple myeloma
  • stage II multiple myeloma
  • refractory multiple myeloma
  • stage III adult Burkitt lymphoma
  • stage III adult Hodgkin lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage III adult diffuse mixed cell lymphoma
  • stage III adult diffuse small cleaved cell lymphoma
  • stage III adult immunoblastic large cell lymphoma
  • stage III adult lymphoblastic lymphoma
  • stage III chronic lymphocytic leukemia
  • stage III grade 1 follicular lymphoma
  • stage III grade 2 follicular lymphoma
  • stage III grade 3 follicular lymphoma
  • stage III mantle cell lymphoma
  • stage III marginal zone lymphoma
  • stage III multiple myeloma
  • stage III small lymphocytic lymphoma
  • stage IV adult Burkitt lymphoma
  • stage IV adult Hodgkin lymphoma
  • stage IV adult diffuse large cell lymphoma
  • stage IV adult diffuse mixed cell lymphoma
  • stage IV adult diffuse small cleaved cell lymphoma
  • stage IV adult immunoblastic large cell lymphoma
  • stage IV adult lymphoblastic lymphoma
  • stage IV chronic lymphocytic leukemia
  • stage IV grade 1 follicular lymphoma
  • stage IV grade 2 follicular lymphoma
  • stage IV grade 3 follicular lymphoma
  • stage IV mantle cell lymphoma
  • stage IV marginal zone lymphoma
  • stage IV small lymphocytic lymphoma
  • Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
  • Philadelphia chromosome positive childhood precursor acute lymphoblastic leukemia
  • refractory chronic lymphocytic leukemia
  • childhood myelodysplastic syndromes
  • stage III adult T-cell leukemia/lymphoma
  • stage IV adult T-cell leukemia/lymphoma
  • adult nasal type extranodal NK/T-cell lymphoma
  • childhood nasal type extranodal NK/T-cell lymphoma
  • stage III cutaneous T-cell non-Hodgkin lymphoma
  • stage IV cutaneous T-cell non-Hodgkin lymphoma
  • recurrent cutaneous T-cell non-Hodgkin lymphoma
  • recurrent adult T-cell leukemia/lymphoma
  • Neoplasms
  • Graft vs Host Disease
  • Leukemia
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Lymphoma, Large-Cell, Immunoblastic

Name

Location

Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Veterans Affairs Medical Center - NashvilleNashville, Tennessee  37212
Vanderbilt-Ingram Cancer Center - Cool SpringsNashville, Tennessee  37064
Vanderbilt-Ingram Cancer Center at FranklinNashville, Tennessee  37064