Chemotherapy in Treating Patients With Myelodysplastic Syndrome Before Donor Stem Cell Transplant

Myelodysplastic Syndrome Clinical Trial

— ICT-HCT  

Official title:

Initial Cytoreductive Therapy for Myelodysplastic Syndrome Prior to Allogeneic Hematopoietic Cell Transplantation (the ICT-HCT Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01812252
• Other study ID #: 2661.00
• Secondary ID: NCI-2013-0053826
• Status: Completed
• Phase: Phase 2
• Start date: August 19, 2013
• Est. completion date: October 26, 2022

Study information

• Verified date: January 2024
• Source: Fred Hutchinson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized clinical trial studies different chemotherapies in treating patients with myelodysplastic syndrome before donor stem cell transplant. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells, and may prevent the myelodysplastic syndrome from coming back after the transplant. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Description:

OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm A: Patients receive decitabine or azacitidine intravenously (IV) or subcutaneously (SC) for 7 days. Treatment repeats every 28 days for 4 cycles of decitabine or 6 cycles of azacitidine in the absence of disease progression or unacceptable toxicity. Arm B: Patients receive induction-like chemotherapy per standard of care or per experimental protocol. This study does not require a specific chemotherapy regimen for Arm B. After completion of study treatment, patients are followed up for 18 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: October 26, 2022
• Est. primary completion date: October 26, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of de novo or secondary myelodysplastic syndrome (MDS), including chronic myelomonocytic leukemia, as defined by the 2008 World Health Organization classification system
• Patients must have measurable disease requiring cytoreduction, defined as a bone marrow myeloblast count >= 5% and < 20% on morphologic examination or by flow cytometry in cases in which adequate morphologic examination is not possible
• Patients must be considered to have an acceptable risk of early mortality with intensive chemotherapy as determined by the attending physician at the time of the initial visit; since the specific therapy within each arm will be determined after randomization, there is no threshold of organ dysfunction or performance status for inclusion
• Considered a potential transplant candidate; the attending/treating physician will determine transplant candidacy at the time of consent
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent

Exclusion Criteria:

• A diagnosis of acute promyelocytic leukemia as defined by the 2008 World Health Organization classification system
• Previous treatment for MDS or acute myeloblastic leukemia (AML) with intensive chemotherapy regimen (induction chemotherapy) or hypomethylating agent
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment
• Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
• Females who are pregnant or breastfeeding
• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment
• Any uncontrolled or significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
• Clinical evidence suggestive of central nervous system (CNS) involvement with MDS unless a lumbar puncture confirms the absence of leukemic blasts in the cerebrospinal fluid (CSF)

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• de Novo Myelodysplastic Syndrome
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Secondary Myelodysplastic Syndrome
• Syndrome

Intervention

Drug:
• Azacitidine (AZC)
Given IV or SC
• Decitabine
Given IV or SC

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Center

Country where clinical trial is conducted

United States, 

References & Publications (16)

De Padua Silva L, de Lima M, Kantarjian H, Faderl S, Kebriaei P, Giralt S, Davisson J, Garcia-Manero G, Champlin R, Issa JP, Ravandi F. Feasibility of allo-SCT after hypomethylating therapy with decitabine for myelodysplastic syndrome. Bone Marrow Transplant. 2009 Jun;43(11):839-43. doi: 10.1038/bmt.2008.400. Epub 2009 Jan 19. — View Citation

Deeg HJ, Storer B, Slattery JT, Anasetti C, Doney KC, Hansen JA, Kiem HP, Martin PJ, Petersdorf E, Radich JP, Sanders JE, Shulman HM, Warren EH, Witherspoon RP, Bryant EM, Chauncey TR, Getzendaner L, Storb R, Appelbaum FR. Conditioning with targeted busulfan and cyclophosphamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood. 2002 Aug 15;100(4):1201-7. doi: 10.1182/blood-2002-02-0527. — View Citation

Estey E, de Lima M, Tibes R, Pierce S, Kantarjian H, Champlin R, Giralt S. Prospective feasibility analysis of reduced-intensity conditioning (RIC) regimens for hematopoietic stem cell transplantation (HSCT) in elderly patients with acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2007 Feb 15;109(4):1395-400. doi: 10.1182/blood-2006-05-021907. Epub 2006 Oct 12. — View Citation

Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, Schoch R, Gattermann N, Sanz G, List A, Gore SD, Seymour JF, Bennett JM, Byrd J, Backstrom J, Zimmerman L, McKenzie D, Beach C, Silverman LR; International Vidaza High-Risk MDS Survival Study Group. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009 Mar;10(3):223-32. doi: 10.1016/S1470-2045(09)70003-8. Epub 2009 Feb 21. — View Citation

Field T, Perkins J, Huang Y, Kharfan-Dabaja MA, Alsina M, Ayala E, Fernandez HF, Janssen W, Lancet J, Perez L, Sullivan D, List A, Anasetti C. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010 Feb;45(2):255-60. doi: 10.1038/bmt.2009.134. Epub 2009 Jun 22. — View Citation

Gerds AT, Gooley TA, Estey EH, Appelbaum FR, Deeg HJ, Scott BL. Pretransplantation therapy with azacitidine vs induction chemotherapy and posttransplantation outcome in patients with MDS. Biol Blood Marrow Transplant. 2012 Aug;18(8):1211-8. doi: 10.1016/j.bbmt.2012.01.009. Epub 2012 Jan 16. — View Citation

Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, Storb R, McDonald GB. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010 Nov 25;363(22):2091-101. doi: 10.1056/NEJMoa1004383. — View Citation

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. Erratum In: Blood 1998 Feb 1;91(3):1100. — View Citation

Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A, Beelen D, Devergie A, Alessandrino E, Willemze R, Ruutu T, Boogaerts M, Falda M, Jouet JP, Niederwieser D, Kroger N, Mufti GJ, De Witte TM. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol. 2010 Jan 20;28(3):405-11. doi: 10.1200/JCO.2009.21.8073. Epub 2009 Dec 14. — View Citation

Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, Sonneveld P, Maertens J, Jongen-Lavrencic M, von Lilienfeld-Toal M, Biemond BJ, Vellenga E, van Marwijk Kooy M, Verdonck LF, Beck J, Dohner H, Gratwohl A, Pabst T, Verhoef G; Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON); German AML Study Group (AMLSG); Swiss Group for Clinical Cancer Research (SAKK) Collaborative Group. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009 Sep 24;361(13):1235-48. doi: 10.1056/NEJMoa0901409. Erratum In: N Engl J Med. 2010 Mar 25;362(12):1155. Dosage error in published abstract; MEDLINE/PubMed abstract corrected; Dosage error in article text. — View Citation

Lubbert M, Bertz H, Ruter B, Marks R, Claus R, Wasch R, Finke J. Non-intensive treatment with low-dose 5-aza-2'-deoxycytidine (DAC) prior to allogeneic blood SCT of older MDS/AML patients. Bone Marrow Transplant. 2009 Nov;44(9):585-8. doi: 10.1038/bmt.2009.64. Epub 2009 Apr 13. — View Citation

Nakai K, Kanda Y, Fukuhara S, Sakamaki H, Okamoto S, Kodera Y, Tanosaki R, Takahashi S, Matsushima T, Atsuta Y, Hamajima N, Kasai M, Kato S. Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome. Leukemia. 2005 Mar;19(3):396-401. doi: 10.1038/sj.leu.2403640. — View Citation

Pautas C, Merabet F, Thomas X, Raffoux E, Gardin C, Corm S, Bourhis JH, Reman O, Turlure P, Contentin N, de Revel T, Rousselot P, Preudhomme C, Bordessoule D, Fenaux P, Terre C, Michallet M, Dombret H, Chevret S, Castaigne S. Randomized study of intensified anthracycline doses for induction and recombinant interleukin-2 for maintenance in patients with acute myeloid leukemia age 50 to 70 years: results of the ALFA-9801 study. J Clin Oncol. 2010 Feb 10;28(5):808-14. doi: 10.1200/JCO.2009.23.2652. Epub 2010 Jan 4. — View Citation

Scott BL, Storer B, Loken MR, Storb R, Appelbaum FR, Deeg HJ. Pretransplantation induction chemotherapy and posttransplantation relapse in patients with advanced myelodysplastic syndrome. Biol Blood Marrow Transplant. 2005 Jan;11(1):65-73. doi: 10.1016/j.bbmt.2004.10.001. — View Citation

Warlick ED, Cioc A, Defor T, Dolan M, Weisdorf D. Allogeneic stem cell transplantation for adults with myelodysplastic syndromes: importance of pretransplant disease burden. Biol Blood Marrow Transplant. 2009 Jan;15(1):30-8. doi: 10.1016/j.bbmt.2008.10.012. — View Citation

Yakoub-Agha I, de La Salmoniere P, Ribaud P, Sutton L, Wattel E, Kuentz M, Jouet JP, Marit G, Milpied N, Deconinck E, Gratecos N, Leporrier M, Chabbert I, Caillot D, Damaj G, Dauriac C, Dreyfus F, Francois S, Molina L, Tanguy ML, Chevret S, Gluckman E. Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French society of bone marrow transplantation. J Clin Oncol. 2000 Mar;18(5):963-71. doi: 10.1200/JCO.2000.18.5.963. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Failure-free Survival (Failure Defined as Death or Relapse)	18-month failure-free survival (failure defined as death or relapse).	18 months
Secondary	Quality of Life Will be Assessed Using the European Organization for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) Questionnaire.	The European Organization for Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) (version 3) is a 30-item cancer-specific questionnaire for measuring the health-related quality of life (QOL) in cancer patients. It includes five functioning scales (physical, PF; role, RF; cognitive, CF; emotional, EF; and social, SF), three symptom scales (fatigue, FA; pain, PA; and nausea and vomiting, NV), a global health status/QOL scale (GL), and six single items (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial impact of the disease and treatment). All items employ a 4-point Likert scale, ranging from 1 (not at all) to 4 (very much) with lower scores representing a better outcome and higher scores a worse outcome; with the exception of two items in the GL scale, which use 7-point scales (1=very poor to 7=excellent) lower scores representing a worse outcome and higher score representing a better outcome.	EORTC QLQ-C30 questionnaire will be collected at screening, after completion of therapy (HMA 4-6 month, and up to 6 months for induction-like chemotherapy) just prior to stem cell infusion and 100 (± 14) days after stem cell infusion (HSCT).
Secondary	Quality of Life Will be Assessed Using the EORTC QLQ-HDC29 a Supplementary Module Assessing the Quality of Life During and After High-dose Chemotherapy and Stem Cell Transplantation.	European Organization for Research and Treatment of Cancer Quality of Life Questionnaire High Dose Chemotherapy (EORTC QLQ-HDC29) is a treatment-specific quality of life questionnaire that addresses treatment specific side effects as well as emotional, social, and family issues for patients treated with high dose regimens and HCT. The QLQ-HDC29 module includes 29 items, consisting of 6 multi-item scales and 8 single-items; all items employ a 4-point Likert scale, ranging from 1 (not at all) to 4 (very much) with lower scores representing a better outcome and higher scores a worse outcome with the exception of question 47 and 52 being the a higher score resulting in a better outcome and lower score a worse outcome.	EORTC QLQ-HDC29 questionnaire will be collected after completion of therapy (HMA 4-6 month, and up to 6 months for induction-like chemotherapy) pre stem cell infusion (HSCT), and 100 (± 14) days post stem cell infusion (HSCT).
Secondary	Overall Survival	The total length of follow-up will be 18 months from the start of treatment (day 1). Four categories were added for participants alive 18 months from start of treatment (day 1) 1) Participants alive after 18 months from start of treatment who received hematopoietic cell transplantation (HCT); 2) Participants alive after 18months from start of treatment who did not receive HCT.; 3) Participants deceased after 18 months from start of treatment who received HCT; 4) Participants deceased after 18 months from start of treatment who did not receive HCT.	Up to 18 months
Secondary	Number of Patients Who Relapse Post-transplant	To compare which of the two, intensive chemotherapy versus hypomethylating agent-based therapy, have a factor of relapse post hematopoietic cell transplantation (HCT).	Up to 18 months
Secondary	Number of Participants Who Received a Hematopoietic Cell Transplantation (HCT).	Frequency at which the participants received a hematopoietic cell transplantation (HCT)	Up to 18 months