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A Phase I/II Study Evaluating the Safety and Efficacy of Intravenous POL6326 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies


Phase 1/Phase 2
18 Years
65 Years
Open (Enrolling)
Both
Leukemia, Lymphoma, Multiple Myeloma

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Trial Information

A Phase I/II Study Evaluating the Safety and Efficacy of Intravenous POL6326 for the Mobilization and Transplantation of HLA-Matched Sibling Donor Hematopoietic Stem Cells in Patients With Advanced Hematological Malignancies


Current protocols use G-CSF to mobilize hematopoietic progenitor cells from matched sibling
and volunteer unrelated donors. Unfortunately, this process requires from four to six days
of G-CSF injection and is associated with significant morbidity, most notably bone pain.
POL6326 is associated with few side effects and collection of cells occurs on the same day
as POL6326 administration.

This study will evaluate the safety and efficacy of this novel agent for hematopoietic
progenitor cell mobilization and allogeneic transplantation based on the following
hypotheses:

1. Donors mobilized with intravenous POL6326 will require fewer collections than have
previously been seen for donors mobilized with subcutaneous AMD3100.

2. Healthy HLA-matched donors receiving one or two infusions of POL6326 will mobilize
sufficient CD34+ cells (at least 2.0 x 106 CD34+ cells/kg recipient weights) following
leukapheresis to support a hematopoietic cell transplant.

3. IV POL6326 will result in more rapid kinetics and a higher maximum (peak) of human
CD34+ stem cells mobilized from human normal allogeneic donors compared to previous
donors who were mobilized with AMD3100.

4. The hematopoietic cells mobilized by IV POL6326 will be functional and will result in
prompt and durable hematopoietic engraftment following transplantation into
HLA-identical siblings with advanced hematological malignancies using various
non-myeloablative and myeloablative conditioning regimens and regimens for routine GVHD
prophylaxis.


Inclusion Criteria:



Donor Inclusion Criteria

- Donor must be 18 to 70 years of age inclusive.

- Donor must be a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

- Donor must have adequate cardiac function with no history of congestive heart failure
and no history of atrial fibrillation or ventricular tachyarrhythmia.

- Donor must have adequate renal function as defined by a minimum creatinine clearance
(CrCl) value of >30 ml/min. In the ongoing study of multiple myeloma patients, those
treated with POL6326 who had a creatinine clearance of 35-58 ml/min showed no
indication that this mild to moderate renal impairment had an impact on safety.

- Donor must have adequate hepatic function as defined by a total bilirubin <3x upper
limit of normal.

- Donor must have adequate neurologic function as defined by NO evidence of a severe
central or peripheral neurologic abnormality and no history of cerebrovascular
accident or seizure disorder requiring anticonvulsant medication.

- Donor must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA licensed
test.

- Donor must have an ECOG performance status of 0 or 1.

- Donor must demonstrate ability to be compliant with study regimen.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.

- Donor must be able to understand and willing to sign an IRB approved written informed
consent document.

Recipient Inclusion Criteria

- Recipient must have available the successful collection of a POL62326 mobilized
product. When an adequate collection (2.0 X 10^6 CD34+ cells/kg/actual recipient
weight) cannot be obtained using two days of IV POL6326, the mobilization will be
considered unsuccessful and G-CSF will be administered per standard institutional
procedures. Some recipients may need to receive a combined product of cells
mobilized with POL6326 and G-CSF. These recipients will not be considered "eligible"
but will be followed per protocol for safety purposes only.

- Recipient must be 18 to 65 years of age inclusive.

- Recipient must have a 6/6 HLA-matched sibling willing to donate PBSC for transplant.

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control, abstinence) prior to study entry and
for the duration of study participation. Should a woman become pregnant or suspect
she is pregnant while participating in this study, she must inform her treating
physician immediately.

- Recipient must have one of the following diagnoses:

- Acute myelogenous leukemia (AML) in 1st or subsequent remission or in relapse,

- Acute lymphoblastic leukemia (ALL) in 1st or subsequent remission or in relapse,

- Myelodysplastic syndrome either intermediate 1 or 2, or high risk by the
International Prognostic Scoring System,

- Chronic myelogenous leukemia (CML) in accelerated or second chronic phase,

- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater
complete remission, partial remission, or refractory relapse,

- Chronic lymphocytic leukemia (CLL), Rai Stage 2-4, failing at least 2 prior
regimens, OR

- Multiple myeloma (MM), Stage 2-3.

- Recipient must have adequate cardiac function with a left ventricular ejection
fraction > 40%.

- Recipient must have adequate pulmonary function defined as NO severe or symptomatic
restrictive or obstructive lung disease, and formal pulmonary function testing
showing an FEV1 >50% of predicted and a DLCO >40% of predicted, corrected for
hemoglobin.

- Recipient must have adequate hepatic function as defined by a total bilirubin <3x
upper limit of normal or absence of hepatic fibrosis/cirrhosis.

- Recipient must have adequate neurologic function as defined by NO evidence of a
severe central or peripheral neurologic abnormality. Patients with a history of
previous CNS tumor involvement are eligible provided they are without symptoms or
signs and the CNS is now free of disease on lumbar puncture and CT scan of the brain.

- Recipient must be HIV-1&2 antibody and HTLV-1&2 antibody sero-negative by FDA
licensed test.

- Recipient must have an ECOG performance status of 0 or 1.

- Recipient must demonstrate ability to be compliant with medical regimen.

- Recipient must have life expectancy of greater than 2 months.

- Recipient must be able to understand and willing to sign an IRB approved written
informed consent document.

Exclusion Criteria:

Donor Exclusion Criteria

- Donor must not have an active infection at the time of study entry.

- Donor must not have active alcohol or substance abuse within 6 months of study entry.

- Donor must not be currently enrolled on another investigational agent study.

- Donor must not have any medical condition, which, in the opinion of the clinical
investigator, would interfere with his/her evaluation.

- Donor must not have an uncontrolled intercurrent illness including, but not limited
to, ongoing or active infection symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements.

- If female and of child-bearing age, donor must not be pregnant or breastfeeding.

Recipient Exclusion Criteria

- Recipient must not have had (the following therapies within the following timeframe):

- Previous allogeneic transplant

- Previous treatment with plerixafor

- Investigative drugs within 21 days

- Recipient must have no evidence of active infection at the time of the transplant
preparative regimen or at time of transplantation.

- Recipient must have no active alcohol or substance abuse within 6 months of study
entry.

- Recipient must not have a history of other malignancy ≤ 5 years previous with the
exception of basal cell or squamous cell carcinoma of the skin which were treated
with local resection only or carcinoma in situ of the cervix.

- Recipients with known brain metastases must be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse
events.

- Recipient must not have a history of allergic reactions attributed to compounds of
similar chemical or biologic composition to POL6326 or other agents used in the
study.

- Recipient must not be pregnant and/or breastfeeding.

- Recipient must not have any medical condition which, in the opinion of the clinical
investigator, would interfere with the evaluation of the patient.

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Phase I Study - safety and toxicity of POL6326 when it is infused over 120 minutes as a mobilization agent.

Outcome Time Frame:

30 days

Safety Issue:

Yes

Principal Investigator

John DiPersio, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Washington University School of Medicine

Authority:

United States: Institutional Review Board

Study ID:

201112026

NCT ID:

NCT01413568

Start Date:

April 2012

Completion Date:

April 2015

Related Keywords:

  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Hematologic Neoplasms

Name

Location

Washington University School of MedicineSaint Louis, Missouri  63110