A Phase 2, Open-Label, Multiple-Dose Study Investigating the Efficacy and Safety of Panhematin in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndrome
The myelodysplastic syndromes (MDS), a diverse group of hematopoietic stem cell (HSC)
disorders, are characterized by ineffective hematopoiesis that manifest clinically as
anemia, neutropenia, and/or thrombocytopenia. MDS is most frequently observed in the
elderly population (median age between 60 and 70 years) and has a male predominance. The
incidence of MDS varies from 2.1 to 12.6 cases per 100,000 people per year, with an
estimated prevalence of up to 55,000 patients in the United States [Catenacci, 2005;
Williamson, 1994; Aul, 1998; Aul, 2001]. Patients with MDS most frequently present with
symptoms of fatigue, pallor, exertional dyspnea, infection, bleeding or bruising [Catenacci,
2005].
MDS can be divided into 2 major subtypes: indolent (or early) MDS, in which pro-apoptotic
forces predominate, and aggressive (or advanced) MDS, in which pro-proliferative factors are
more common.
The only curative therapy for MDS is allogeneic transplantation [Catenacci, 2005; Thompson,
2005]. Curative treatments are restricted to younger, healthier individuals with
histocompatible-matched donors or those able to undergo intensive chemotherapeutic regimens
[Catenacci, 2005]. Recently, the FDA approved 3 agents for the treatment of this disease,
Vidaza, Dacogen, and revlimid. The latter is approved for a subset of patients with MDS
with del 5q abnormality, the former two are more applicable to higher risk disease. Rhu-EPO
is currently available to patients with low risk MDS however, if they fail, their options
are limited to the agents mentioned above, all of which have significant myelotoxic effects.
Effective and less myelosuppressive treatments for low-risk MDS are needed.
We are proposing a novel approach for the treatment of patients with low-risk MDS using heme
supplementation with Panhematin® (hemin for injection). Panhematin® is an iron-containing
metalloporphyrin, indicated for the amelioration of recurrent attacks of acute intermittent
porphyria; it acts to limit the hepatic and/or marrow synthesis of porphyrin, presumably, as
a result of the inhibition of aminolevulinic acid synthetase (the enzyme which limits the
rate of porphyrin/heme biosynthetic pathway) [Panhematin® Product Prescribing Information].
There are pre-clinical and clinical data to suggest that heme supplementation with
Panhematin® (hematin for injection) has potential as a treatment option for patients with
MDS. Preliminary data indicate hemin administration has the potential to stimulate
progenitor cell growth, stimulate globin synthesis, and elevate overall hemoglobin levels.
Panhematin® has been proven to be well tolerated when used therapeutically in patients with
acute intermittent porphyria, and it is anticipated to be well tolerated in this patient
population. For this study, selected patients will have low or intermediate 1 risk disease
by IPSS, and the standard of care for MDS (supportive therapies) will be administered as
needed. Measurement of serum porphyrin levels and Hgb F will be done at baseline and at
week 8.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response rate (i.e., the number and percentage of patients demonstrating a complete response, partial response, or overall response) to Panhematin® at Week 8 (as defined by the International Working Group (IWG).
6 months
No
Jamile Shammo, MD
Principal Investigator
Rush University Medical Center
United States: Food and Drug Administration
MDS 2005-01
NCT00467610
April 2007
January 2009
Name | Location |
---|---|
Rush University Medical Center | Chicago, Illinois 60612-3824 |
The University of Texas M. D. Anderson Cancer Center | Houston, Texas 77030 |