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MT2008-15: Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Nonmyeloablative Preparative Regimen and Priming With Complement 3a Fragment (C3a)


Phase 1/Phase 2
18 Years
75 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma, Myelodysplastic Syndromes

Thank you

Trial Information

MT2008-15: Transplantation of Unrelated Donor Umbilical Cord Blood in Patients With Hematological Malignancies Using a Nonmyeloablative Preparative Regimen and Priming With Complement 3a Fragment (C3a)


OUTLINE:

- Nonmyeloablative preparative regimen: Patients receive fludarabine phosphate IV over 1
hour on days -6 to -2 and cyclophosphamide IV over 2 hours on day -6. Patients then
undergo total-body irradiation on day -1. Some patients also receive anti-thymocyte
globulin IV every 12 hours on days -6, -5, and -4.

- Umbilical cord blood (UCB) transplantation: Patients undergo unmanipulated UCB
transplantation followed by complement 3a fragment primed UCB transplantation on day 0.

Treatment for graft-vs-host disease prophylaxis is also given.

After completion of study therapy, patients are followed up periodically for up to 2 years.


Inclusion Criteria:



- Disease Criteria

- Acute Leukemias: Must be in remission by morphology (<5% blasts). Note
cytogenetic relapse or persistent disease without morphologic relapse is
acceptable. Also a small percentage of blasts that is equivocal between marrow
regeneration vs. early relapse are acceptable provided there are no associated
cytogenetic markers consistent with relapse. (See exclusion criteria for more
detailed definition)

- Acute myeloid leukemia: high risk CR1 (as evidenced by preceding myelodysplastic
syndrome (MDS), high risk cytogenetics such as those associated with MDS or
complex karyotype, > 2 cycles to obtain complete remission (CR) or
erythroblastic and megakaryocytic); second or greater CR.

- Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk
cytogenetics (e.g. t(9;22, t(1;19), t(4;11), other MLL rearrangements) or > 1
cycle to obtain CR; second or greater CR.

- Burkitt's lymphoma in CR2 or subsequent CR

- Natural Killer cell malignancies

- Myeloproliferative syndromes/diseases: Chronic myelogenous leukemia (CML) in
chronic or accelerated phase but patients must have failed or been intolerant to
Imatinib mesylate. EXCLUDED: CML in refractory blast crisis, myelofibrosis,
polycythemia vera, and essential thrombocytosis.

- Myelodysplastic Syndrome: any subtype including refractory anemia (RA) if severe
pancytopenia, high risk complex cytogenetics or International Prognostic Scoring
System (IPSS) ≥ intermediate-2 (Int-2). Blasts must be less than 5%. If 5% or
more requires therapy pre-transplant to reduce blast count to ≤5%. Patients who
receive single agent 5-azacytidine, decitabine or immunomodulating drugs are
eligible.

- Large-cell lymphoma, Hodgkin's lymphoma and multiple myeloma: patients with
chemotherapy sensitive disease that has failed or who are ineligible for an
autologous transplant. Patients are eligible for umbilical cord blood (UCB)
transplantation if there is no evidence of progressive disease by imaging
modalities and/or biopsy. Persistent PET activity, though possibly related to
lymphoma, IS NOT an exclusion criterion in the absence of computated tomography
(CT) changes in size indicating progression. Large-cell and Hodgkin's lymphoma
that is progressive on salvage therapy is NOT eligible. Patients with stable
disease are eligible for transplantation if the largest residual nodal mass is <
5 cm (approximately). For patients who have responded to preceding therapy, the
largest residual mass must represent a 50% reduction and be < 7.5 cm
(approximately).

- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone
B-cell lymphoma, follicular lymphoma which have progressed after at least two
prior therapies. Patients with bulky disease should be considered for debulking
chemotherapy before transplant. Patients with refractory disease are eligible,
unless has bulky disease and an estimated tumor doubling time of less than one
month. Patients with stable disease are eligible for transplantation if the
largest residual nodal mass is < 5 cm (approximately). For patients who have
responded to preceding therapy, the largest residual mass must represent a 50%
reduction and be < 7.5 cm (approximately).

- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are
eligible after initial therapy if chemotherapy sensitive. Mantle-cell lymphoma
that is progressive on salvage therapy is NOT eligible. Patients with stable
disease are eligible for transplantation if the largest residual nodal mass is <
5 cm (approximately). For patients who have responded to preceding therapy, the
largest residual mass must represent a 50% reduction and be < 7.5 cm
(approximately).

- Umbilical Cord Blood Graft Selection - Two UCB units will be compose the graft, and
each unit must be a 4-6 HLA-A, B, DRB1 antigen match to each other, as well as a 4-6
antigen match to the recipient. The combined cryopreserved nucleated cell dose of the
2 units must be ≥ 3 X 10^7/kg with each unit having a minimum cell dose of 1.5 X
10^7/kg. UCB units will be selected according to a common umbilical cord blood graft
selection algorithm

- Performance Status - adequate performance status defined as Karnofsky score ≥ 60

- Age 18 to 70 years of age; patients ≥ 70 but ≤ 75 years are eligible if the
co-morbidity score is ≤ 2

- Organ Function

- Cardiac: Left ventricular ejection fraction > 35%; absence of decompensated
congestive heart failure; absence of uncontrolled arrhythmia

- Pulmonary: DLCO > 30% of predicted; absence of O2 requirements

- Hepatic: ALT, AST, alkaline phosphatase and bilirubin < 5 x upper limit of
normal

- Renal: Creatinine ≤ 2 mg/dl (patients with a creatinine > 1.2 or history of
renal dysfunction must have calculated glomerular filtration rate (GFR) > 40
mL/min/1.73m2)

- If recent mold infection e.g. Aspergillus - must have minimum of 30 days of
appropriate treatment before transplant and infection controlled and be cleared
by Infectious Disease.

- The following conditions must be met:

- If prior myeloablative autologous transplant, must be > 3 months but ≤ 12
months from transplant OR have received at least 2 cycles of multi-agent or
highly immunosuppressive chemotherapy (i.e. induction for acute leukemia)
within the 3 months preceding this study. OR

- If neither prior myeloablative autologous transplant ≤ 12 months from
transplant nor have received at least 2 cycles of multi-agent or highly
immunosuppressive chemotherapy (i.e. induction for acute leukemia) within
the 3 months preceding this study, patients are eligible as long as they
receive equine anti-thymocyte globulin as part of the conditioning regimen.

Exclusion Criteria:

- Patients who have an available, medically suitable, 5-6/6 HLA-A, B, DRB1 matched
sibling donor

- Patients who are eligible for autologous transplantation

- Prior allogeneic transplant

- Acquired or inherited bone marrow failure syndromes such as aplastic anemia and
Fanconi anemia

- Pregnant or breast feeding

- Evidence of HIV infection or known HIV positive serology

- Current uncontrolled serious infection

- Active central nervous system malignancy

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Proportion of patients with the complement 3a (C3a) unit predominating

Outcome Description:

Efficacy of the pre-incubation of one of two umbilical cord blood (UCB) units with C3a as part of a unrelated donor double UCB nonmyeloablative transplantation in patients with high-risk hematological malignancies.

Outcome Time Frame:

Day 180

Safety Issue:

No

Principal Investigator

Claudio G. Brunstein, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota

Authority:

United States: Food and Drug Administration

Study ID:

2008LS097

NCT ID:

NCT00963872

Start Date:

March 2010

Completion Date:

August 2014

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

University of Minnesota Medical Center - FairviewMinneapolis, Minnesota  55455