Trial Of Double Umbilical Cord Blood Transplantation
Condition: Hematological Malignancies
MeSH terms: Hematologic Neoplasms
Intervention: Full intensity, double umbilical cord, stem cell transplant; Flu/Bu4 conditioning regimen; Total Lymphoid Irradiation (TLI); Graft versus Host Disease prevention (GVHD prophylaxis); Mycophenolate Mofetil
Intervention description: stem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation; Fludarabine: 40 mg/m² daily on days -5, -4, -3, -2
Busulfan: 3.2 mg/kg IV daily on days -5, -4, -3, -2; one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion; Tacrolimus for GVHD (Graft Versus Host Disease Prevention) Tacrolimus - will begin on day -3 (IV or oral) for at least 180 days. Target trough level for tacrolimus is 8-12 ng/ml. In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant.; Mycophenolate Mofetil (MMF) for GVHD prophylaxis. MMF - will be given at a dose of 10mg/kg IV q 8 hours if the patient weight is more than 50 kg, or 15 mg/kg IV q 8 hours if less than 50 kg, beginning the morning of day -3. (If renal failure and Glomerular Filtration Rate (GFR) < 25 mL/min, the dose should not exceed 1 gm every 8 hours. (No dose adjustment for liver disease is required.) MMF should be given via IV until oral medications are tolerated.
MMF will be stopped at Day +28 if no acute GVHD is seen by that time. If there is not any donor cell engraftment, MMF will be continued as directed by the attending physician. If the patient has active acute GVHD requiring systemic therapy, MMF may be continued.
Intervention MeSH terms: Mycophenolic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Maximum age: 65 Years
Healthy volunteers: No
Keywords: umbilical cord blood; stem cell transplant; leukemia; multiple myeloma; lymphoma

Summary:

      This pilot research study is to investigate the safety and effectiveness of stem cell
      transplantation to treat blood-related (hematopoietic) cancers, using stem cells collected
      from two different, umbilical cord blood donors. Subjects in this study are receiving a stem
      cell transplant because other treatments have failed or their disease is unlikely to respond
      to other treatment options.

      Blood-related cancers can be treated and sometimes cured with very high doses of chemotherapy
      and radiation therapy, given to kill the cancer cells; however, these treatments can prove
      unsuccessful and can harm normal cells in the bone marrow or a patient's disease may be
      unlikely to respond to these treatment options.

      Hematopoietic stem cells transplantation (HSCT) is a potential cure, but opportunities to
      perform HSCT are limited by donor availability. Only 20-30% of patients may have matched
      family donors. In some cases, a mismatched family donor may be suitable. For patients needing
      a transplant who do not have a suitably matched family donor, blood stem cells from matched
      unrelated donors can be used. The length of time required to identify a matched unrelated
      donor presents another obstacle for patients waiting to receive an HSCT.

      Blood stem cells are found in umbilical cord blood (UCB), which is blood left over in the
      placenta (afterbirth) after a baby is born. Usually this blood is discarded with the
      placenta, but over the past 15 years, we have learned how to collect and freeze cord blood
      cells to be used for transplants at a later time. A cord blood unit is the cord blood cells
      collected and stored from a single placenta. More than 6,500 umbilical cord blood stem cell
      transplants have been done worldwide, mostly in children with leukemia. One important factor
      affecting the success of a cord blood transplant is the cell dose (number of stem cells in
      the cord blood unit / recipient's weight). Patients who receive a high cell dose (> 2.5 x 107
      cells/kilogram) have better marrow recovery and a higher rate of survival than those who
      receive a lower cell dose.

      In an attempt to make UCB transplantation possible for bigger children, adolescents and
      adults, researchers have tried giving two cord blood units on the same day for their
      transplant, one after the other. The data from more than 150 "double cord blood" transplants
      in adults suggest that the "double cord blood" transplants may allow bone marrow recovery and
      survival in patients who do not have a single cord blood unit with enough cells for
      successful transplantation.

      This is a pilot study to research the safety and effectiveness of using two UCB units in
      adult and pediatric UCB transplantation when combined with a conditioning regimen called
      Flu/Bu4/TLI (consisting of fludarabine, busulfan and total lymphoid irradiation).
    

Eligibility criteria:

        Inclusion Criteria:

          -  The candidate must have an incurable hematological malignancy or non-malignant
             hematological disorder and be eligible for transplant by the University of Michigan
             program.

          -  The candidate must have a life expectancy of less than one year without
             transplantation.

          -  The candidate must have two partially HLA-matched UCB (cord blood) units.Units must be
             HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular
             typing) and DRB1 (at high resolution by molecular typing) loci. Units must be
             HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with each other (using same resolution of
             molecular typing as indicated above).

          -  The candidate must have access to two appropriately HLA-matched units that are
             available such that one unit delivers a pre-cryopreserved nucleated cell dose of at
             least 2.5 x 107 per kilogram and the second unit at least 2.0 x 107 per kilogram.

        Exclusion Criteria:

          -  The candidate is an adult or pediatric patient who has a suitable related or unrelated
             donor available for transplant. Suitable donors include 8/8 (HLA-A,B,C and DR, with
             all loci high-resolution typing) or 7/8 related or unrelated donor available within 42
             days of search initiation.

          -  The candidate has a Karnofsky (Adult) or Lansky (Pediatrics) performance status of <
             70% at the time of admission for HSCT.

          -  The candidate is a patient with evidence of HIV infection.

          -  The candidate is a patient with active bacterial, fungal or viral infection not
             responding to treatment. Non-response to treatment is determined by body temperature,
             blood culture results, and radiographic findings as applicable.

          -  The candidate is pregnant.

          -  The candidate has any medical comorbidities/conditions that, in the opinion of the
             transplant team, would keep the patient from complying with the needs of the protocol
             and/or would markedly increase the morbidity and mortality from the procedure.

          -  The candidate has any conditions, in the opinion of the transplant team, such as
             substance abuse, or severe personality disorder that would keep the patient from
             complying with the needs of the protocol and would markedly increase the morbidity and
             mortality from the procedure.