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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

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndrome

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Trial Information

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,

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.

Inclusion Criteria:

A patient will be eligible for study participation if all of the following criteria are

1. The patient must sign and date the IRB/IEC approved Informed Consent Form/HIPAA
Authorization prior to study participation.

2. Patient is at least 18 years of age.

3. If female:

1. Patient, either male or female, is either not of childbearing potential, defined
as postmenopausal for at least 1 year or surgically sterile (bilateral tubal
ligation, bilateral oophorectomy or hysterectomy), or if of childbearing
potential, must comply with an effective method of birth control acceptable to
the Investigator during the study (oral contraceptives, Depo-Provera,
intra-uterine device), for at least 1 month prior to enrollment and for 1 month
following the completion of the study.

2. Patient is not breastfeeding.

3. Patient of childbearing potential must have a negative urine or serum pregnancy
test during the screening period.

4. Patient has a diagnosis of low- or intermediate-1 risk MDS, as determined by the
International Prognostic Scoring (IPSS) (score of 0-1).

5. Patient must be transfusion dependent (i.e., received ≥ 2 units over an 8-week period
prior to registration) or have a hemoglobin value ≤ 10 g/dL on the screening

6. Patients must have ≤ 10% blasts in the bone marrow and peripheral blood.

7. Patient must have a platelet counts > 50,000/microliters and absolute neutrophil
counts (ANC) >500/microliters.

8. Patient must have adequate hepatic and renal functions, defined as serum bilirubin,
serum glutamic-oxaloacetic transaminase (SGOT), and serum glutamate pyruvate
transaminase (SGPT) ≤ 2 times the upper limit of normal (ULN), and creatinine ≤ 1.5
times the ULN.

9. Patient must have an ECOG score of ≤ 2.

10. The patient has a negative human immunodeficiency virus antibody (HIV) test result.

Exclusion Criteria:

A patient will be ineligible for study participation if any of the following criteria are

1. The patient has a history of an allergic reaction or significant sensitivity to

2. The patient has taken or used any investigational drug or device in the 30 days prior
to screening.

3. The patient has chronic myelomonocytic leukemia (CMML).

4. The patient has a history of deep vein thrombosis or known hypercoagulable state.

5. The patient has a history of a pre-existing medical condition that, in the opinion of
the investigator, will interfere with the participation in the study.

6. The patient has poor peripheral venous access, if central venous access is not

7. The patient has an uncontrolled active infection.

8. The patient has positive test results for hepatitis B surface antigen, and hepatitis
C virus antibody.

9. The patient has any other condition or prior therapy that, in the opinion of the
Investigator, would make the patient unsuitable for the study.

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:

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).

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Jamile Shammo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Rush University Medical Center


United States: Food and Drug Administration

Study ID:

MDS 2005-01



Start Date:

April 2007

Completion Date:

January 2009

Related Keywords:

  • Myelodysplastic Syndrome
  • myelodysplastic
  • MDS
  • Panhematin
  • Hemin
  • Myelodysplastic Syndromes
  • Preleukemia



Rush University Medical Center Chicago, Illinois  60612-3824
The University of Texas M. D. Anderson Cancer Center Houston, Texas  77030