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A Phase II Trial of Transplants From HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies and Other Lethal Hematologic Disorders

Phase 2
69 Years
Open (Enrolling)
Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Multiple Myeloma

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Trial Information

A Phase II Trial of Transplants From HLA-Compatible Related or Unrelated Donors With CD34+ Enriched, T-cell Depleted Peripheral Blood Stem Cells Isolated by the CliniMACS System in the Treatment of Patients With Hematologic Malignancies and Other Lethal Hematologic Disorders

Inclusion Criteria:

- Malignant conditions for which CD34+ selected, T-cell depleted allogeneic
hematopoietic stem cell transplantation is indicated such as:

- AML in 1st remission - for patients whose AML does not have 'good risk' cytogenetic
features (i.e. t 8;21, t15;17, inv 16).

- Secondary AML in 1st remission

- AML in 1st relapse or > 2nd remission

- ALL/LL in 1st remission clinical or molecular features indicating a high risk for
relapse; or ALL > 2nd remission

- CML failing to respond to or not tolerating Imatinib or dasatinib in first chronic
phase of disease; CML in accelerated phase second chronic phase or in CR after
accelerated phase or blast crisis.

- Non-Hodgkins lymphoma with chemoresponsive disease in any of the following

1. intermediate or high grade lymphomas who have failed to achieve a first CR or
have relapsed following a 1st remission who are not candidates for autologous

2. any NHL in remission which is considered not curable with chemotherapy alone and
not eligible/appropriate for autologous transplant.

- Myelodysplastic syndrome (MDS): RA/RCMD with high risk cytogenetic features or
transfusion dependence as well as RAEB-1 and RAEB-2 and Acute myelogenous leukemia
(AML) evolved from MDS, who are not eligible for transplantation under protocol IRB

- Chronic myelomonocytic leukemia: CMML-1 and CMML-2.

- Multiple Myeloma with disease in the following categories:

1. Patients with relapsed multiple myeloma following autologous stem cell
transplantation who have achieved at least partial response following additional

2. Patients with high risk cytogenetics at diagnosis must have achieved a partial
response following autologous stem cell transplantation. Patients must have
complex karyotype, del17p, t4;14 and/or t14;16 by FISH and/or del13 by

- Other rare lethal disorders of Hematopoiesis and Lymphopoiesis for which a T-cell
depleted transplant is indicated (e.g. hemophagocytic lymphohistiocytosis; refractory
aplastic anemia or congenital cytopenias; non-SCID lethal genetic immunodeficiencies
such as Wiskott Aldrich Syndrome, CD40 ligand deficiency, or ALPS, as well as
refractory autoimmune cytopenias, PNH, metabolic storage diseases or heavily
transfused congenital hemoglobinopathies).

- Accrual to each treatment arm will include up to 30 standard risk and 30 poor risk
patients (60 patients/treatment arm) except for Regimen D, which will include 30
patients/treatment arm, all of which will be poor risk by virtue of risks of relapse
and/or transplant related mortality.

- Standard risk patients will include eligible patients, as defined above, who are
receiving transplants as treatment for MDS in RA/RCMD, AML in 1st or 2nd remission,
ALL in 1st CR, NHL in 1st remission, MM in 1st remission, Very Good Partial Response,
or 1st Partial Response or CML in the first chronic phase or 1st remission.

- All other patients, including those with treatment related malignancies and/or those
who have AML derived from MDS, will have received extensive prior chemo/radiotherapy
and, therefore, will be considered to be at poor risk of conditioning and transplant
related morbidities, and potentially transplant related mortality. Patients with life
threatening non-malignant genetic and acquired disorders will also, by virtue of
their history of, optional transfusions and/or infection be considered poor risk.
Stopping rules for non-relapse related mortality in these heavily treated patients
are, therefore, slightly less stringent than patients in the poor risk transplant
groups. Stopping rules for the principal endpoints of graft failure and GvHD are the
same for all groups.

The following inclusion criteria are also required:

- Patient's age includes from birth on to < 70 years old.

- Patients may be of either gender or any ethnic background.

- Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status > or
= to 70%

- Patients must have adequate organ function measured by:

Cardiac: asymptomatic or if symptomatic then LVEF at rest must be > 50% and must improve
with exercise. Hepatic: < 3x ULN ALT and < 1.5 total serum bilirubin, unless there is
congenital benign hyperbilirubinemia.

Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range,
then CrCl > 40 ml/min (measured or calculated/estimated) Pulmonary: asymptomatic or if
symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

- Each patient must be willing to participate as a research subject and must sign an
informed consent form.

Exclusion Criteria:

- Female patients who are pregnant or breast-feeding

- Active viral, bacterial or fungal infection

- Patient seropositive for HIV-I/II; HTLV -I/II

- Presence of leukemia in the CNS.


Inclusion Criteria:

- HLA compatible related or unrelated donor, (i.e. a fully matched or 1-2 HLA allele
disperate donor).

- Meets criteria outlined in the FACT-approved SOP for "DONOR EVALUATION AND SELECTION

Transplant Program Manual, document E-1 (see attached, or link to URL:

- Donor should agree to undergo general anesthesia and bone marrow harvest collection
if PBSC yield is inadequate or otherwise not transplantable for whatever reason.

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

- Wt >25kg. Donor Exclusion Criteria

- Evidence of active infection (including urinary tract infection, or upper respiratory
tract infection) or viral hepatitis exposure (on screening), unless only HBS Ab+ 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., 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:

To assess the incidence of durable hematopoietic engraftment for T-cell depleted transplants fractionated by the CliniMACS system administered after each of the four disease targeted cytoreduction regimens.

Outcome Time Frame:

3 years

Safety Issue:


Principal Investigator

Richard O'Reilly, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2010

Completion Date:

May 2014

Related Keywords:

  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • Multiple Myeloma
  • Leukemia
  • Multiple Myeloma
  • radiation
  • Thiotepa
  • cyclophosphamide
  • fludarabine
  • Clofarabine
  • CliniMACS device
  • GCSF
  • 10-050
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia
  • Hematologic Neoplasms



Memorial Sloan Kettering Cancer Center New York, New York  10021