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Myeloablative Unrelated Donor Cord Blood Transplantation With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cells for Patients With High Risk Hematological Malignancies

Phase 2
2 Years
70 Years
Open (Enrolling)
Leukemia, Myelodysplastic Syndrome, Lymphoma

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Trial Information

Myeloablative Unrelated Donor Cord Blood Transplantation With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cells for Patients With High Risk Hematological Malignancies

Inclusion Criteria:

Note: protocol eligible patients according to the criteria outlined below will then be
divided according to age, diagnosis, performance status, organ function, prior
transplantation, hematopoietic cell transplant comorbidity index (HCT-CI)23, and CB TNC
dose into those who are at standard risk (Arm A) or high risk (Arm B) for early
post-transplant death for the purposes of applying stopping rules and outcome analysis.


o 2 - 70 years.

Diagnosis of high risk hematological malignancy:

Any acute leukemia in first complete remission (CR) considered at high risk for relapse,
or second or third CR, or relapse/refractory less than 25% blasts in bone marrow, or
aplasia post-therapy. This includes de novo acute leukemia or acute leukemia that is
therapy related or arising from an antecedent hematologic disorder including
myelodysplasia (MDS), chronic myeloid leukemia (CML) or other myeloproliferative disorder.

- Juvenile myelomonocytic leukemia (JMML) in CR, or relapse with less than 25% bone
marrow blasts.

- CML with tyrosine kinase inhibitor failure in chronic or accelerated phase or evolved
to acute leukemia.

- MDS with life-threatening cytopenia(s), and/or red blood cell or platelet transfusion
dependence, or patients with aplasia, or patients with excess blasts less than 25%
blasts in the bone marrow at work-up.

- Aggressive lymphoma: patients in CR1 with disease at high risk of relapse or CR2-3 or

- Indolent lymphoma or chronic lymphocytic leukemia (CLL): any disease status provided
any transformed component is in CR.

- Hodgkin's lymphoma that is primary refractory or relapsed not suitable for other

Performance status:

- Karnofsky score > or = to 70 or Lansky score > or = to 70.

• Organ function:

- Left ventricular ejection fraction (LVEF) > or = to 50%.

- Spirometry & corrected DLCO > or = to 50% predicted. In small children use history
and physical and CT scan to determine pulmonary status.

- Total bilirubin < than or = to 1.5 ULN (unless benign congenital elevated bilirubin);
ALT/ AST < than or = to 2.5 x upper limit of normal (ULN).

- Calculated creatinine (calc. creat.) clearance > than or = to 60 ml/min.

- Albumin > than or = to 3.0.


o Cryopreserved dose will be > than or = to 1.5 x 107 TNC/kilogram in each unit for double
unit CB grafts. This will be the CB graft for the majority of patients.

In select pediatric patients with access to CB units that have high TNC (> 5.0 x 10^7/kg),
good HLA-match (5/6 or 6/6) and are from good quality CB banks a single unit could be
considered with a back-up CB unit on standby.

- In select patients who have a very poor search and only have one suitable CB unit
available, this unit could be given as a single unit. This unit must have a TNC > 2.5
x 10^7 TNC/kilogram.

- Haploidentical donors will be used as outlined in section 6.4. Related donors with up
to 8/10 match to the patient can be used Assignment of conditioning intensity (high
dose vs reduced intensity) will be based on patient disease status, age, extent of
prior therapy, organ function and presence of significant comorbidities as outlined
in Section 9.2.

For the purposes of analysis, patients will be assigned to Arms A and B as summarized
below according to their risk of early post-transplant death.

Eligible patients who fulfill all of the following criteria will be assigned to risk Arm

Age 2-49 years Diagnosis Any acute leukemia in CR1 - CR2 (includes therapy-related and
arising from MDS or myeloproliferative disease). JMML in CR. CML with TKI failure & < 5%
blasts. MDS with < 5% blasts at work-up. Lymphoma (including CLL) CR1-2.

Performance Status Karnofsky > or = to 80; Lansky > or = to 80 Organ Function LVEF > or =
to 60% Spirometry & corrected DLCO > or = to 80% predicted. Total bilirubin normal; ALT/
AST normal-1.4 x ULN. Calc. creat. clearance > or = to 70 ml/min.

Prior HSC Transplant No HCT-CI score23 0-2 Pre-thaw TNC Dose Each unit > or = to 2.0 x

Eligible patients who meet any of the following criteria will be assigned to risk Arm B:

Age 50-70 years Diagnosis Any acute leukemia in relapse/ refractory disease in BM or
circulating blasts or CR3 or aplasia. JMML not in CR. MDS with aplasia or > or = to 5%
blasts. Lymphoma (including CLL) with disease other than CR1-2. Severe myelofibrosis of
the bone marrow Performance Status Karnofsky 70; Lansky 70 Organ Function LVEF 50-59%.
Spirometry & corrected DLCO 50-79% predicted. Total bilirubin 1.1-1.5 normal; ALT/ AST
1.5-2.5 x ULN. Calc. creat. clearance 60-69 ml/min. Prior HSC Transplant Yes HCT-CI
score23 3 or higher Pre-thaw TNC Dose Either or both units 1.5-1.9 x 10^7/kg.

Exclusion Criteria:

- Active CNS leukemia.

- Any acute leukemia (including prior myelodysplasia or CML blast crisis) with
morphologic relapse or persistent disease > 25% blasts in the BM, or doubling of
the blasts in the blood in the 2 weeks preceding admission, or need for
hydroxyurea in the 2 weeks prior to admission, or uncontrolled extra-medullary

- Two prior stem cell transplants.

- One prior stem cell transplant within the preceding 6 months.

- Prior radiation therapy rendering patient ineligible for TBI.

- Uncontrolled viral, bacteria or fungal infection at time of study enrollment.

- Sero-positive or NAT positive for HIV.

- Females who are pregnant or breast feeding.

- Patient or guardian unable to give informed consent or unable to comply with the
treatment protocol including appropriate supportive care, follow-up, and
research tests

Cord Blood Grafts:

Units will be selected based on the HLA-match to the patient and individual cell doses of
the units according to current MSKCC unit selection criteria. HLA-testing will be done
using molecular techniques. The standard cord blood graft for this protocol will consist
of 2 units as a double unit graft. Each unit will be at least 4 of 6 HLA-A, -B antigen and
-DRB1 allele matched with the recipient. Each unit will have a cryopreserved dose of at
least 1.5 x 10^7 TNC/recipient body weight (TNC/kg). In the occasional pediatric patient
with a large well matched good quality single unit or the rare patient with only one unit
of suitable match and dose characteristics the cord blood graft can consist of a single

Haploidentical Donor

Inclusion Criteria:

A HLA-haploidentical related donor will be selected using an algorithm designed to
maximize NK cell alloreactivity with prioritization according to KIR/HLA genotypes.

- Donor CMV status will also be taken into account.

- The donor must meet criteria outlined in the FACT-approved SOP for "DONOR EVALUATION
Program Manual, document E-1 (see attached, or link to URL:

- The donor must have adequate peripheral venous catheter access for leukapheresis or
must agree to placement of a central catheter.

- The donor must be >25 kg in weight.

Haploidentical Donor Exclusion Criteria:

Evidence of active infection (including active urinary tract infection, or upper
respiratory tract infection) or evidence of viral hepatitis exposure on screening unless
only HbsAb+ and HBV DNA negative.

- Medical or physical reason which makes the donor unlikely to tolerate or cooperate
with growth factor therapy and leukapheresis.

- Factors which place the donor at increased risk for complications from leukapheresis
or G-CSF therapy (e.g., active autoimmune disease, sickle cell trait, symptomatic
coronary artery disease requiring therapy).

- Pregnancy (positive serum or urine β-HCG) or breastfeeding. Women of childbearing age
must avoid becoming pregnant while on the study.

Type of Study:


Study Design:

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

Outcome Measure:

number of days to neutrophil recovery

Outcome Description:

The day of neutrophil recovery is defined as the first of 3 consecutive days in which the absolute neutrophil count (ANC) is > 0.5. The cumulative incidence of neutrophil recovery will be reported at day 45 post-transplant. Sustained neutrophil engraftment is neutrophil engraftment without secondary graft failure. This will be analyzed at 1 and 2 years post-transplant.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Juliet Barker, M.B.B.S.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

September 2016

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndrome
  • Lymphoma
  • G-CSF
  • Cord Blood Transplantation
  • CliniMACS
  • 12-153
  • Leukemia
  • Lymphoma
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms



Memorial Sloan-Kettering Cancer Center New York, New York  10021