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Myelodysplastic SyndromePhase 2NCT00467610

Phase 2, Open-Label, Multi-Dose Study of Panhematin in Patients With MDS

A Phase 2 study testing Panhematin in people with Myelodysplastic Syndrome, run by Rush University Medical Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is a Phase II, open-label clinical trial examining the role of Panhematin® in patients with MDS. The objective of this study is to evaluate the safety and efficacy of Panhematin® (hematin for injection) in the treatment of adult patients (≥ 18 years of age) with low-risk MDS. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndrome
What is being tested?
Panhematin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
May 2007to Jan 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A patient will be eligible for study participation if all of the following criteria are met:
  • The patient must sign and date the IRB/IEC approved Informed Consent Form/HIPAA Authorization prior to study participation.
  • Patient is at least 18 years of age.
  • If female:
  • 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.
  • Patient is not breastfeeding.
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  • Patient of childbearing potential must have a negative urine or serum pregnancy test during the screening period.
  • Patient has a diagnosis of low- or intermediate-1 risk MDS, as determined by the International Prognostic Scoring (IPSS) (score of 0-1).
  • 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 laboratories.
  • Patients must have ≤ 10% blasts in the bone marrow and peripheral blood.
  • Patient must have a platelet counts > 50,000/microliters and absolute neutrophil counts (ANC) >500/microliters.
  • 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.
  • Patient must have an ECOG score of ≤ 2.
  • The patient has a negative human immunodeficiency virus antibody (HIV) test result.

Who cannot join

  • A patient will be ineligible for study participation if any of the following criteria are met:
  • The patient has a history of an allergic reaction or significant sensitivity to Panhematin®.
  • The patient has taken or used any investigational drug or device in the 30 days prior to screening.
  • The patient has chronic myelomonocytic leukemia (CMML).
  • The patient has a history of deep vein thrombosis or known hypercoagulable state.
  • 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.
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  • The patient has poor peripheral venous access, if central venous access is not available.
  • The patient has an uncontrolled active infection.
  • The patient has positive test results for hepatitis B surface antigen, and hepatitis C virus antibody.
  • The patient has any other condition or prior therapy that, in the opinion of the Investigator, would make the patient unsuitable for the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Rush University Medical Center

    Chicago, Illinois, 60612

Other trials in United States

About this study

Official title: 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

This is a Phase II, open-label clinical trial examining the role of Panhematin® in patients with MDS. The objective of this study is to evaluate the safety and efficacy of Panhematin® (hematin for injection) in the treatment of adult patients (≥ 18 years of age) with low-risk MDS.

The study will be conducted on an outpatient basis and will consist of the following:

  • A Screening Period (within 28 days of the Day 1)
  • Screening bone marrow aspiration and biopsy up to 60 days prior to receiving study medication
  • An 8-week Treatment Period (Days 1 through 4 of Week 1, and weekly visits during Weeks 2 through 8); partial and complete responders in any of the three cell lines may continue treatment for an additional 4 weeks
  • A 6-month Post treatment Follow-up Period (monthly clinic visits during Weeks 12 40)
Read the detailed description

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.

Being tested
Panhematin
Keywords
myelodysplastic, MDS, Panhematin, Hemin
Medical subject headings
Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PanhematinDrug

Study groups in NCT00467610
Study groupRoleWhat they receive
PanhematinExperimentalNot described
Receives: Drug: Panhematin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Tolerability of Panhematin®.

    Number of patients with no adverse events.

    Measured: participants were followed during therapy with panhematin, and up to six months post completion of therapy, average of 8 months.

  2. Response Rate ( CR+PR) at Week 8, Based on the IWG Criteria for Response Assessment ( 2000 Version)

    Complete response(CR): <5% blasts in the bone marrow,with normal maturation of all cell lines, Hemoglobin >11 g/dL, neutrophils>1500/mm3 platelets>100,000/mm3.

    Partial response (PR): >50% decrease in blasts, or less advanced IPSS than pretreatment value, same hematological parameters as in CR.

    Stable disease (SD): No evidence of disease progression in bone marrow, stable peripheral blood counts failure: Increase in bone marrow blast percentage, progression to more advanced IPSS than pretreatment and worsening of cytopenias.

    (Cheson, 2000)

    Measured: After 8 weeks of therapy with panhematin

Secondary outcomes (2)

  1. Number of Patients Demonstrating Hematological Improvement to Panhematin® at Week 4.

    Hematological improvement (HI)

    Major:

    HI-Erythroid:>2 g/dL rise in hemoglobin, or transfusion independence HI-Neutrophil: Absolute increase of >500/mm3, or >100% increase HI-Platelet: Absolute increase of >30,000, or transfusion independence

    Minor:

    HI-Erythroid:1 to 2 g/dL increase in hemoglobin or 50% decrease in transfusion dependence.

    HI-P: For patients with pretreatment platelet count < 100,000/mm3, ≥ 50% increase with a net increase > 10,000/mm3 but < 30,000/mm3.

    HI-N: For patients with pretreatment ANC < 1500/mm3, ≥ 100% increase, but < 500/mm3 increase.

    Measured: 4 weeks after initiation of treatment with Panhematin

  2. Hematological Improvement Rate at Week 8 as Defined by the IWG 2000 Criteria for Response Assessment, 2000 Version

    Measured: At 8 weeks from start of therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Apr 2007 (estimated)
  2. Study startMay 2007
  3. Primary completionDec 2008
  4. Study completionJan 2009

Why it stopped: lack of efficacy.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00467610
Sponsor's protocol ID
MDS 2005-01
Other IDs
06011001
Status last verified
Oct 2014
First submitted
26 Apr 2007
Last updated
24 Oct 2014
Data monitoring committee
Yes

Publications

  • Aul C, Germing U, Gattermann N, Minning H. Increasing incidence of myelodysplastic syndromes: real or fictitious? Leuk Res. 1998 Jan;22(1):93-100. doi: 10.1016/s0145-2126(97)00089-1.

    PubMed 9585086

  • Aul C, Giagounidis A, Germing U. Epidemiological features of myelodysplastic syndromes: results from regional cancer surveys and hospital-based statistics. Int J Hematol. 2001 Jun;73(4):405-410. doi: 10.1007/BF02994001.

    PubMed 11503953

  • Catenacci DV, Schiller GJ. Myelodysplasic syndromes: a comprehensive review. Blood Rev. 2005 Nov;19(6):301-19. doi: 10.1016/j.blre.2005.01.004.

    PubMed 15885860

  • Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, Lowenberg B, Beran M, de Witte TM, Stone RM, Mittelman M, Sanz GF, Wijermans PW, Gore S, Greenberg PL; World Health Organization(WHO) international working group. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-4.

    PubMed 11090046

  • Dhar GJ, Bossenmaier I, Cardinal R, Petryka ZJ, Watson CJ. Transitory renal failure following rapid administration of a relatively large amount of hematin in a patient with acute intermittent porphyria in clinical remission. Acta Med Scand. 1978;203(5):437-43. doi: 10.1111/j.0954-6820.1978.tb14903.x.

    PubMed 665312

  • Fibach E, Kollia P, Schechter AN, Noguchi CT, Rodgers GP. Hemin-induced acceleration of hemoglobin production in immature cultured erythroid cells: preferential enhancement of fetal hemoglobin. Blood. 1995 May 15;85(10):2967-74.

    PubMed 7537986

  • Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, Sanz M, Vallespi T, Hamblin T, Oscier D, Ohyashiki K, Toyama K, Aul C, Mufti G, Bennett J. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997 Mar 15;89(6):2079-88.

    PubMed 9058730

  • Mauritzson N, Albin M, Rylander L, Billstrom R, Ahlgren T, Mikoczy Z, Bjork J, Stromberg U, Nilsson PG, Mitelman F, Hagmar L, Johansson B. Pooled analysis of clinical and cytogenetic features in treatment-related and de novo adult acute myeloid leukemia and myelodysplastic syndromes based on a consecutive series of 761 patients analyzed 1976-1993 and on 5098 unselected cases reported in the literature 1974-2001. Leukemia. 2002 Dec;16(12):2366-78. doi: 10.1038/sj.leu.2402713.

    PubMed 12454741

  • McHale CM, Winter PC, Lappin TR. Erythroid gene expression is differentially regulated by erythropoietin, haemin and delta-aminolaevulinic acid in UT-7 cells. Br J Haematol. 1999 Mar;104(4):829-37. doi: 10.1046/j.1365-2141.1999.01269.x.

    PubMed 10192446

  • Monette FC, Holden SA. Hemin enhances the in vitro growth of primitive erythroid progenitor cells. Blood. 1982 Aug;60(2):527-30.

    PubMed 7093531

  • Panhematin® Product Prescribing Information. Abbott Laboratories, August 2000 Edition

  • Porter PN, Meints RH, Mesner K. Enhancement of erythroid colony growth in culture by hemin. Exp Hematol. 1979 Jan;7(1):11-6.

    PubMed 428474

  • Rund D, Ben-Yehuda D. Therapy-related leukemia and myelodysplasia: evolving concepts of pathogenesis and treatment. Hematology. 2004 Jun;9(3):179-87. doi: 10.1080/10245330410001701503.

    PubMed 15204099

  • Thompson JE, Luger SM. The role of hematopoietic stem cell transplantation in myelodysplastic syndrome. Oncology (Williston Park). 2005 Apr;19(4):533-42; discussion 542-4, 547-8.

    PubMed 15934520

  • Timonen TT, Kauma H. Therapeutic effect of heme arginate in myelodysplastic syndromes. Eur J Haematol. 1992 Nov;49(5):234-8. doi: 10.1111/j.1600-0609.1992.tb00054.x.

    PubMed 1473585

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Panhematin in people with Myelodysplastic Syndrome, run by Rush University Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Oct 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of Panhematin®. (time frame: participants were followed during therapy with panhematin, and up to six months post completion of therapy, average of 8 months.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00467610, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2014.

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