ACTIVE_NOT_RECRUITING

Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia

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Conditions

Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaHigh Risk Myelodysplastic SyndromeMyelodysplastic Syndrome

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial studies how well total marrow and lymphoid irradiation works as a conditioning regimen before hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute leukemia. Total body irradiation can lower the relapse rate but has some fatal side effects such as irreversible damage to normal internal organs and graft-versus-host disease (a complication after transplantation in which donor's immune cells recognize the host as foreign and attack the recipient's tissues). Total body irradiation is a form of radiotherapy that involves irradiating the patient's entire body in an attempt to suppress the immune system, prevent rejection of the transplanted bone marrow and/or stem cells and to wipe out any remaining cancer cells. Intensity-modulated radiation therapy (IMRT) is a more recently developed method of delivering radiation. Total marrow and lymphoid irradiation is a method of using IMRT to direct radiation to the bone marrow. Total marrow and lymphoid irradiation may allow a greater dose of radiation to be delivered to the bone marrow as a preparative regimen before hematopoietic cell transplant while causing less side effects to normal organs than standard total body irradiation.

Official Title

Phase II Study of Evaluating the Efficacy of Total Marrow and Lymphoid Irradiation (TMLI) as the Conditioning Regimen for HLA-Haploidentical Hematopoietic Cell Transplantation in Patients With Myelodysplasia or Acute Leukemia

Quick Facts

Study Start:2020-02-07
Study Completion:2026-06-23
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04262843

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:12 Years to 60 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:CHILD, ADULT
Inclusion CriteriaExclusion Criteria
  1. * Documented informed consent of the participant and/or legally authorized representative
  2. * Karnofsky performance status \>= 70
  3. * Histologically confirmed diagnosis of one the following:
  4. * Patients with acute myelogenous leukemia
  5. * In first complete remission (CR1) with intermediate or poor risk cytogenetics according to National Comprehensive Cancer Network (NCCN) guidelines for acute myeloid leukemia (AML) or European LeukemiaNet (ELN) 2017
  6. * In second complete remission (CR2) or third complete remission (CR3)
  7. * Patients with chemosensitive active disease
  8. * Patients with acute lymphocytic leukemia
  9. * In CR1 with poor risk cytogenetics:
  10. * For adults according to NCCN guidelines for acute lymphoblastic leukemia (ALL): Patients older than 40 year of age; with high white blood cell count (WBC) at diagnosis (\>= 30,000 for B lineage or \>= 50,000 for T lineage), or with high risk cytogenetics including: hypoploidy (\< 44 chromosomes); t(v;11q23): MLL rearranged; t(9;22) (q34;q11.2); complex cytogenetics (5 or more chromosomal abnormalities)
  11. * For pediatrics t(9;22), iAMP21loss of 13q, and abnormal 17p
  12. * In CR2 or CR3
  13. * Patients with chemosensitive active disease
  14. * Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories by International Prognostic Scoring System (IPSS) or revised (R)-IPSS
  15. * Total bilirubin =\< 2 X upper limit of normal (ULN) (unless has Gilbert's disease) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
  16. * Creatinine clearance of \>= 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
  17. * Ejection fraction measured by echocardiogram or multigated acquisition scan (MUGA) \>= 50% (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
  18. * Note: To be performed within 28 days prior to day 1 of protocol therapy
  19. * If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and carbon monoxide diffusing capability test (DLCO) (diffusion capacity) \>= 50% of predicted (corrected for hemoglobin). If unable to perform pulmonary function tests: oxygen (O2) saturation \> 92% on room air
  20. * Note: To be performed within 28 days prior to day 1 of protocol therapy
  21. * Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin \[RPR\]) (to be performed within 28 days prior to day 1 of protocol therapy unless otherwise stated)
  22. * If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  23. * Meets other institutional and federal requirements for infectious disease titer requirements
  24. * Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
  25. * Women of childbearing potential (WOCBP): negative urine or serum pregnancy test
  26. * If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  27. * Agreement by females and males of childbearing potential\* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
  28. * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \> 1 year (women only)
  29. * The recipient must have a related donor genotypically human leukocyte antigen (HLA)-A, B,C and DRB1 loci haploidentical to the recipient
  30. * No HLA matched sibling or matched unrelated donor is available
  31. * Patients should be off all previous intensive therapy, chemotherapy or radiotherapy for 3 weeks prior to commencing therapy on this study
  32. * (NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors \[TKIs\]. FLT-3 inhibitors such as sorafenib, crenolanib, midostaurin can also be given up to 3 days before conditioning regimen.)
  33. * DONOR: The donor must be examined and have specific tests performed according to existing institutional guidelines to evaluate his/her candidacy as a donor including the following:
  34. * DONOR: Age =\< 60 years of age
  35. * DONOR: For younger donors, no more than 20 mL bone marrow may be harvested per kg of donor body weight
  36. * DONOR: Medical history and physical examination confirm good health status as defined by institutional standards
  37. * DONOR: Seronegative for HIV Ag, HIV 1+2 Ab, HTLV I/II Ab, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) (IgM and IgG), HCV Ab, RPR for syphilis within 30 days of apheresis collection
  38. * DONOR: Genotypically haploidentical as determined by HLA typing, preferably a nonmaternal HLA haploidentical relative due to data of high incidence of graft failure with use of maternal HLA haploidentical cells. Eligible donors include biological parents, siblings or half siblings, or children
  39. * DONOR: Female donors of child-bearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) test within seven days of mobilization
  40. * DONOR: The donor must have been informed of the investigational nature of this study and have signed a consent form in accordance with Federal Guidelines and the guidelines of the participating institution
  41. * DONOR: Selection of a haploidentical donor will require absence of pre-existing donor-directed anti-HLA antibodies in the recipient
  1. * Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
  2. * Patient may not be receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous three weeks from conditioning
  3. * (NOTE: Low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted. These include: Hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors \[TKIs\]. FLT-3 inhibitors such as sorafenib, crenolanib, midostaurin can also be given up to 3 days before conditioning regimen.)
  4. * Herbal medications dependency
  5. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  6. * No intercurrent illness or other malignancy (other than non-melanoma skin cancer)
  7. * Active infection requiring antibiotics
  8. * Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  9. * Females only: Pregnant or breastfeeding
  10. * Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
  11. * Patients who had a prior autologous or allogeneic transplant
  12. * Patients who had prior radiation therapy of more than 20% of bone marrow containing areas or to any area exceeding 2000 cGy
  13. * Patients with HLA-matched or partially matched (7/8 or 8/8) related or fully matched unrelated donor available to donate
  14. * Patients who have received more than 3 prior regimens, where the regimen intent was to induce remission
  15. * Patients with treatment history including anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)
  16. * Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
  17. * DONOR: Evidence of active infection
  18. * DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis
  19. * DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy
  20. * DONOR: HIV positive

Contacts and Locations

Principal Investigator

Monzr M Al Malki
PRINCIPAL_INVESTIGATOR
City of Hope Medical Center

Study Locations (Sites)

City of Hope Medical Center
Duarte, California, 91010
United States

Collaborators and Investigators

Sponsor: City of Hope Medical Center

  • Monzr M Al Malki, PRINCIPAL_INVESTIGATOR, City of Hope Medical Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-02-07
Study Completion Date2026-06-23

Study Record Updates

Study Start Date2020-02-07
Study Completion Date2026-06-23

Terms related to this study

Additional Relevant MeSH Terms

  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • High Risk Myelodysplastic Syndrome
  • Myelodysplastic Syndrome