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

NCT00467610 | Terminated Phase 2 Results DMC

• 2 other identifiers: MDS 2005-0106011001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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. 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)

Conditions

Myelodysplastic Syndrome

Keywords

myelodysplastic; MDS; Panhematin; Hemin

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability of Panhematin®.

  Number of patients with no adverse events.

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

• 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)

  After 8 weeks of therapy with panhematin

Secondary Outcomes (2)

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

  4 weeks after initiation of treatment with Panhematin

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

  At 8 weeks from start of therapy

Study Arms (1)

Panhematin

EXPERIMENTAL

Drug: Panhematin

Interventions

Panhematin DRUG

Panhematin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Rush University Medical Center: lead
• H. Lundbeck A/S: collaborator

Study Sites (1)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Related Publications (18)

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  PMID: 9585086 BACKGROUND

• 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.

  PMID: 11503953 BACKGROUND

• 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.

  PMID: 15885860 BACKGROUND

• 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.

  PMID: 11090046 BACKGROUND

• 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.

  PMID: 665312 BACKGROUND

• 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.

  PMID: 7537986 BACKGROUND

• 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.

  PMID: 9058730 BACKGROUND

• 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.

  PMID: 12454741 BACKGROUND

• 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.

  PMID: 10192446 BACKGROUND

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

  PMID: 7093531 BACKGROUND

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

  BACKGROUND

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

  PMID: 428474 BACKGROUND

• 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.

  PMID: 15204099 BACKGROUND

• 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.

  PMID: 15934520 BACKGROUND

• 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.

  PMID: 1473585 BACKGROUND

• Volin L, Ruutu T, Knuutila S, Tenhunen R. Heme arginate treatment for myelodysplastic syndromes. Leuk Res. 1988;12(5):423-31. doi: 10.1016/0145-2126(88)90062-8.

  PMID: 3379975 BACKGROUND

• Williamson PJ, Kruger AR, Reynolds PJ, Hamblin TJ, Oscier DG. Establishing the incidence of myelodysplastic syndrome. Br J Haematol. 1994 Aug;87(4):743-5. doi: 10.1111/j.1365-2141.1994.tb06733.x.

  PMID: 7986716 BACKGROUND

• Vidaza® Product Prescribing Information. Pharmion Corporation, 5-18-04 Edition

  BACKGROUND

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Hemin

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Heme; Metalloporphyrins; Porphyrins; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Macrocyclic Compounds; Polycyclic Compounds; Pigments, Biological; Biological Factors

Results Point of Contact

• Title: Jamile shammo
• Organization: Rush university medical center

jamile_shammo@rush.edu

312-942-5157

Study Officials

• Jamile Shammo, MD

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine and Pathology

Study Record Dates

• First Submitted: April 26, 2007
• First Posted: April 30, 2007
• Study Start: May 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: January 1, 2009
• Last Updated: October 24, 2014
• Results First Posted: October 24, 2014

Record last verified: 2014-10

Locations

US (1)