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Phase II Study: HSCT Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit

Phase 2
18 Years
65 Years
Open (Enrolling)
Leukemia, Lymphocytic, Acute, Leukemia, Lymphocytic, Chronic, Leukemia, Myelocytic, Acute, Leukemia, Myeloid, Chronic, Lymphoma, Non-Hodgkin, Lymphoma, Hodgkins

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Trial Information

Phase II Study: HSCT Using CD34 Selected Mismatched Related Donor and One Umbilical Cord Unit

This method of stem cell transplantation is designed to overcome some of the limitations of
other alternative donor transplant options. Use of unrelated umbilical cord unit (UCB)
donors appears to allow a greater degree of HLA mismatch with acceptable rates of GVHD.
However, when UCB transplant was studied in the adult population, investigators discovered
several limitations. One major limitation with UCB was delayed engraftment, resulting in
higher risk of infection in the early post transplant period. The limitations to cord blood
transplant involve delayed engraftment resulting in early complications such as infections.
The main limitation associated with haploidentical donors is the significant
immunosuppression required to prevent/treat aGVHD. Use of this combined modality of
transplantation appears to allow for rapid neutrophil engraftment from the haploidentical
donor and coupled with long term hematopoiesis from the UCB donor, thus requiring less long
term immunosuppression.

This study tests a new method of bone marrow transplantation called combined
haploidentical-cord blood transplantation. In this procedure, some of the blood forming
cells (the stem cells) from a partially HLA matched (haploidentical) related donor are
collected from the blood, as well as cells from an umbilical cord are transplanted into the
patient (the recipient) after administration of a "conditioning regimen". A conditioning
regimen consists of chemotherapy and sometimes radiation to the entire body (total body
irradiation, or TBI),

One of two 'conditioning regimens' which will be determined by the physician.


Fludarabine 30mg/m2(Days-7,-6,-5,-4,-3)-,Melphalan 70mg/m2(Day -3,-2), ATG

2. FLUDARABINE, BUSULFAN, 400 CGY TBI, ATG Fludarabine 50mg/m2(Day
-6,-5,-4,-3,-2),Busulfan 3.2mg/kg(Day -5,-4,-3,-2) 400cGY Total Body
Irradiation(TBI)Day-1,ATG 1.5mg/kg(Day-7,-5,-3,-1)

Day 0 -Haploidentical donor and one umbilical cord blood unit infusion

Filgrastim will be administered daily from day +1 until blood counts have completely
recovered. Tacrolimus and another immunosuppressant, Cellcept, starting before transplant
also to reduce the risks of graft versus host disease and to promote the growth of the
graft. Tacrolimus will be given daily from two days before the transplant until at least
three months after transplantation. Cellcept, will be tapered after the cells engraft.

Inclusion Criteria:

- Patients ≥ 18 years old

- Patient has a related family member(haploidentical) or unrelated which is 5 of 10
HLA identical match.

Standard Risk

- Acute myelogenous leukemia: CR1 with high risk cytogenetics or molecular
abnormalities such as FLT-3 ITD, or CR2 with a first remission that must have lasted
> 1 year.

- Acute Lymphocytic Leukemia: CR1, in order to be standard risk must NOT have
Philadelphia Chromosome.

- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): Must be
refractory to fludarabine or fail to have a complete or partial response after
therapy with a regimen containing fludarabine (or another nucleoside analog, e.g.
2-CDA, pentostatin) or experience disease relapse within 12 months after completing
therapy with a regimen containing fludarabine (or another nucleoside analog).

- Chronic myelogenous leukemia: resistant to or intolerant of TKI, in CP1 or CP2, or
with a mutation that suggests resistance to TKI.

- Myelodysplastic Syndrome: RA, RARS, must be IPSS ≥ INT-2, Blasts <5%.

High Risk Patients:

- Acute myelogenous leukemia: Patients with CR2 are considered high risk if they have
high risk cytogenetics, or molecular abnormalities or CR1 lasted for less than 1
year. Any evidence of active disease or no blasts in an acellular marrow.

- Acute Lymphocytic Leukemia: CR1- with Ph+ disease, CR2/+ with any cytogenetics. Any
evidence of active disease.

- Chronic myelogenous leukemia- CP2/+, AP1/+, resistant or intolerant to TKI.

- Hodgkin's or Non Hodgkin's lymphoma- Disease recurrence following an autologous
transplant, or high risk disease not thought to benefit from autologous transplant.

- Chronic lymphocytic leukemia- that is resistant to fludarabine, and never has been in
remission or with stable disease/progressive disease

- Multiple myeloma: Must have had prior treatment. Patients with high risk cytogenetics
in CR1 may be considered. Previous autologous transplant allowed, however, must have
been greater than 6 months prior to undergoing this transplant.

- Myelodysplastic syndrome: RAEB, CMML

- Other Myeloproliferative disorders including myelofibrosis, spent phase p Vera or
Essential thrombocytosis.

Exclusion Criteria:

- Patients <18 years old Disease related criteria

- APML, presence of t(15,17) in first CR

- Patients with good risk AML, for example t(8;21), or inv 16, or normal
cytogenetics with FLT-3-ITD negative, NPM-1 positive disease in 1st CR

- MDS IPSS < INT-2 Miscellaneous Criteria

- Recipients who have a matched related sibling or unrelated donor

- If recipient has evidence of anti-HLA antibodies directed against cord or
haplo-donor as determined byflowPRA.

Underlying health criteria:

- Zubrod performance status > 2 (see Appendix E)

- Life expectancy is limited to less than 8 weeks by concomitant illness

- Patients with severely decreased LVEF (EF < 40%)

- Impaired pulmonary function tests (PFT's) (FVC, FEV1, DLCO < 45% predicted)

- Estimated Creatinine Clearance <50 ml/min

- Serum bilirubin> 2.0 mg/dl or SGPT >3 x upper limit of normal

- Evidence of chronic active hepatitis or cirrhosis

- HIV-positive

- Patient is pregnant

- Patient or guardian not able to provide informed consent

Type of Study:


Study Design:

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

Outcome Measure:

The primary objective is to estimate the overall survival, separately in the two risk strata.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Jeanne Palmer, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Medical College of Wisconsin


United States: Institutional Review Board

Study ID:

MCW 11491



Start Date:

July 2009

Completion Date:

July 2019

Related Keywords:

  • Leukemia, Lymphocytic, Acute
  • Leukemia, Lymphocytic, Chronic
  • Leukemia, Myelocytic, Acute
  • Leukemia, Myeloid, Chronic
  • Lymphoma, Non-Hodgkin
  • Lymphoma, Hodgkins
  • Unrelated Umbilical Cord Blood Transplant(UCB)
  • CD34+ Selected mismatched related donor
  • Haploidentical donor
  • hematopoietic stem cell transplantation(HSCT)
  • ALL
  • Leukemia, Lymphocytic, Acute
  • AML
  • Leukemia, Myelocytic, Acute
  • CML
  • Leukemia, Myeloid, Chronic
  • NHL
  • Lymphoma, Non-Hodgkin
  • HL
  • Lymphoma, Hodgkins
  • Hodgkin Disease
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphoma
  • Lymphoma, Non-Hodgkin



Froedtert Hospital/ Medical College of Wisconsin - Clinical Cancer CenterMilwaukee, Wisconsin  53226