search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Fludarabine
Fludarabine Phosphate
Granulocyte Colony-Stimulating Factor
Hematopoietic Cell Transplantation
Intensity-Modulated Radiation Therapy
Mycophenolate Mofetil
Tacrolimus
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

12 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Documented informed consent of the participant and/or legally authorized representative
  • Karnofsky performance status >= 70
  • Histologically confirmed diagnosis of one the following:

    • Patients with acute myelogenous leukemia

      • 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
      • In second complete remission (CR2) or third complete remission (CR3)
      • Patients with chemosensitive active disease
    • Patients with acute lymphocytic leukemia

      • In CR1 with poor risk cytogenetics:
    • 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)
    • For pediatrics t(9;22), iAMP21loss of 13q, and abnormal 17p

      • In CR2 or CR3
      • Patients with chemosensitive active disease
    • Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories by International Prognostic Scoring System (IPSS) or revised (R)-IPSS
  • 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)
  • 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)
  • 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)

    • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • 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

    • Note: To be performed within 28 days prior to day 1 of protocol therapy
  • 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)

    • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed
  • Meets other institutional and federal requirements for infectious disease titer requirements

    • Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy
  • Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

    • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • 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

    • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • The recipient must have a related donor genotypically human leukocyte antigen (HLA)-A, B,C and DRB1 loci haploidentical to the recipient
  • No HLA matched sibling or matched unrelated donor is available
  • Patients should be off all previous intensive therapy, chemotherapy or radiotherapy for 3 weeks prior to commencing therapy on this study

    • (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.)
  • 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:
  • DONOR: Age =< 60 years of age
  • DONOR: For younger donors, no more than 20 mL bone marrow may be harvested per kg of donor body weight
  • DONOR: Medical history and physical examination confirm good health status as defined by institutional standards
  • 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
  • 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
  • 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
  • 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
  • DONOR: Selection of a haploidentical donor will require absence of pre-existing donor-directed anti-HLA antibodies in the recipient

Exclusion Criteria:

  • Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection
  • Patient may not be receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous three weeks from conditioning

    • (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.)
  • Herbal medications dependency
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • No intercurrent illness or other malignancy (other than non-melanoma skin cancer)
  • Active infection requiring antibiotics
  • Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  • Females only: Pregnant or breastfeeding
  • 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
  • Patients who had a prior autologous or allogeneic transplant
  • Patients who had prior radiation therapy of more than 20% of bone marrow containing areas or to any area exceeding 2000 cGy
  • Patients with HLA-matched or partially matched (7/8 or 8/8) related or fully matched unrelated donor available to donate
  • Patients who have received more than 3 prior regimens, where the regimen intent was to induce remission
  • Patients with treatment history including anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg)
  • 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)
  • DONOR: Evidence of active infection
  • DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis
  • DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy
  • DONOR: HIV positive

Sites / Locations

  • City of Hope Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (fludarabine, TMLI, HCT, cyclophosphamide)

Arm Description

CONDITIONING: Patients receive fludarabine IV QD on days -7 to -5, and undergo TMLI BID on days -4 to 0 in the absence of disease progression or unacceptable toxicity. TRANSPLANT: Patients undergo hematopoietic cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV QD on days 3-4 in the absence of disease progression or unacceptable toxicity. Beginning on day 5, patients also receive granulocyte colony stimulating factor and tacrolimus/mycophenolate mofetil per institutional standard.

Outcomes

Primary Outcome Measures

Incidence of adverse events
Evaluated using the Bearman scale and National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Graft-versus-host disease (GvHD) free relapse-free survival

Secondary Outcome Measures

Overall survival
Relapse-free survival
Time to relapse/progression
Non-relapse mortality
Incidence of adverse events that meet grade 3, 4, or 5 per CTCAE version 5.0
Incidence of acute GvHD of grades 2-4 and 3-4
Incidence of chronic GvHD
Incidence of infection
Complete remission proportion
Rate of neutrophil recovery
Measured from stem cell infusion to the first to three consecutive days with neutrophil count greater than 0.5 x 10^9/l.
Incidence of cytokine release syndrome
Defined and graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Full Information

First Posted
February 3, 2020
Last Updated
September 21, 2023
Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT04262843
Brief Title
Total Marrow and Lymphoid Irradiation as Conditioning Regimen Before Hematopoietic Cell Transplantation in Patients With Myelodysplastic Syndrome or Acute Leukemia
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2020 (Actual)
Primary Completion Date
February 4, 2024 (Anticipated)
Study Completion Date
February 4, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
City of Hope Medical Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
PRIMARY OBJECTIVE: I. Evaluate the efficacy of the haploidentical hematopoietic cell transplantation (haploHCT) total marrow and lymphoid organ irradiation (TMLI), with high dose post-transplant cyclophosphamide (PTCy) as graft-versus host disease (GvHD) prophylaxis, as assessed by 1-year graft versus (vs) host disease-free relapse-free survival (GRFS) rate in each arm (Arm A: patients with acute myeloid leukemia [AML] or myelodysplastic syndrome [MDS] and Arm B: Patients with acute lymphoblastic leukemia [ALL]). SECONDARY OBJECTIVES: I. Estimate overall survival (OS), cumulative incidences of relapse/disease progression, and non-relapse mortality (NRM) in each arm at 100 days, and 1 year post-transplant. II. Estimate rate of relapse and non-relapse mortality (NRM) at 1 year post-transplant. III. Estimate rates of acute and chronic GvHD, infections, complete remission and neutrophil recovery. IV. Describe and characterize cytokine release syndrome (CRS) post-haploidentical HCT with TMLI as conditioning regimen and PTCy as GvHD prophylaxis as assessed by incidence, frequency and severity. V. Further evaluate the safety of this regimen by assessing: Va. Adverse events: type, frequency, severity, attribution, time course, duration. Vb. Complications: including acute/chronic GVHD, infection and delayed engraftment. EXPLORATORY OBJECTIVES: I. Characterize minimal residual disease from bone marrow aspirates and investigate the possible association between TMLI-based regimen and patient's disease status. II. Describe the kinetics of immune cell recovery. III. Describe the kinetics of serum pro-inflammatory cytokines and GvHD biomarkers. IV. Longitudinal and spatial assessment of TMLI effect on bone marrow environment. V. Cellular and molecular assessment of TMLI effect on bone marrow environment and TMLI effect on the engraftment and disease relapse. OUTLINE: CONDITIONING: Patients receive fludarabine intravenously (IV) once daily (QD) on days -7 to -5, and undergo TMLI twice daily (BID) on days -4 to 0 in the absence of disease progression or unacceptable toxicity. TRANSPLANT: Patients undergo hematopoietic cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV QD on days 3-4 in the absence of disease progression or unacceptable toxicity. Beginning on day 5, patients also receive granulocyte colony stimulating factor and tacrolimus/mycophenolate mofetil per institutional standard. After completion of study treatment, patients are followed up twice weekly for the first 100 days post-transplant, twice monthly until 6 months post-transplant, monthly until patient discontinues immunosuppressive therapy, and then yearly for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment (fludarabine, TMLI, HCT, cyclophosphamide)
Arm Type
Experimental
Arm Description
CONDITIONING: Patients receive fludarabine IV QD on days -7 to -5, and undergo TMLI BID on days -4 to 0 in the absence of disease progression or unacceptable toxicity. TRANSPLANT: Patients undergo hematopoietic cell transplantation on day 0. GVHD PROPHYLAXIS: Patients receive cyclophosphamide IV QD on days 3-4 in the absence of disease progression or unacceptable toxicity. Beginning on day 5, patients also receive granulocyte colony stimulating factor and tacrolimus/mycophenolate mofetil per institutional standard.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fluradosa
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Fludarabine Phosphate
Other Intervention Name(s)
2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Granulocyte Colony-Stimulating Factor
Other Intervention Name(s)
Colony Stimulating Factor 3, Colony-Stimulating Factor (Granulocyte), Colony-Stimulating Factor 3, CSF3, G CSF, G-CSF, Granulocyte Colony Stimulating Factor, Pluripoietin
Intervention Description
Growth factor therapy
Intervention Type
Procedure
Intervention Name(s)
Hematopoietic Cell Transplantation
Other Intervention Name(s)
HCT, Hematopoietic Stem Cell Transplantation, HSCT, Stem Cell Transplant, stem cell transplantation
Intervention Description
Undergo hematopoietic cell transplantation
Intervention Type
Procedure
Intervention Name(s)
Intensity-Modulated Radiation Therapy
Other Intervention Name(s)
IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy
Intervention Description
Undergo TMLI
Intervention Type
Drug
Intervention Name(s)
Mycophenolate Mofetil
Other Intervention Name(s)
Cellcept, MMF
Intervention Description
Immunosuppressive therapy
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Other Intervention Name(s)
FK 506, Fujimycin, Hecoria, Prograf, Protopic
Intervention Description
Immunosuppressive therapy
Primary Outcome Measure Information:
Title
Incidence of adverse events
Description
Evaluated using the Bearman scale and National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame
Up to day 100
Title
Graft-versus-host disease (GvHD) free relapse-free survival
Time Frame
Time from start of protocol therapy to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, death, relapse/progression, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
Time from start of protocol therapy to death from any cause, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Title
Relapse-free survival
Time Frame
Time from the start of protocol therapy to the date of death, disease relapse, or last follow-up, whichever comes first, assessed up to 2 years post-transplant.]
Title
Time to relapse/progression
Time Frame
Time from the start of protocol therapy to death, disease relapse or progression, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Title
Non-relapse mortality
Time Frame
Time from start of therapy until non-disease related death, or last follow-up, whichever comes first, assessed up to 2 years post-transplant
Title
Incidence of adverse events that meet grade 3, 4, or 5 per CTCAE version 5.0
Time Frame
From day -9 to day -1, from day 0 to day 30, and day 31 to day 100 post-transplant
Title
Incidence of acute GvHD of grades 2-4 and 3-4
Time Frame
From date of stem cell infusion to documented/biopsy proven acute GVHD onset date (within the first 100 days post-transplant)
Title
Incidence of chronic GvHD
Time Frame
From approximately 80-100 days post-transplant to the documented/biopsy proven chronic GvHD onset date
Title
Incidence of infection
Time Frame
From day 0 to day 100 post-transplant
Title
Complete remission proportion
Time Frame
At day 30
Title
Rate of neutrophil recovery
Description
Measured from stem cell infusion to the first to three consecutive days with neutrophil count greater than 0.5 x 10^9/l.
Time Frame
Up to 2 years
Title
Incidence of cytokine release syndrome
Description
Defined and graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Time Frame
Up to 2 years
Other Pre-specified Outcome Measures:
Title
Minimal residual disease
Description
Assessed from bone marrow aspirates.
Time Frame
At day 30, 100, and 180 days, and 1 year post-transplant
Title
Immune cell recovery
Description
Immunophenotyping with lymphocyte subsets by flow cytometry, including but not limited to the following cell markers: CD4, CD8, CD56, CD16, etc.
Time Frame
Up to 2 years
Title
GvHD biomarker analysis
Description
Will be done by standard enzyme-linked immunosorbent (ELISA) assays.
Time Frame
Up to 2 years
Title
Pro-inflammatory cytokine analysis
Description
Will be done using standard ELISA assays.
Time Frame
Up to 2 years
Title
Effect of TMLI on bone marrow environment
Description
Longitudinal assessment swill be done by dual energy computed tomography (DECT), water-fat magnetic resonance imaging (wfMRI) imaging. Biological assessment of bone marrow samples will be done by flow cytometry, colony forming assay, and immunohistochemistry studies.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Documented informed consent of the participant and/or legally authorized representative Karnofsky performance status >= 70 Histologically confirmed diagnosis of one the following: Patients with acute myelogenous leukemia 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 In second complete remission (CR2) or third complete remission (CR3) Patients with chemosensitive active disease Patients with acute lymphocytic leukemia In CR1 with poor risk cytogenetics: 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) For pediatrics t(9;22), iAMP21loss of 13q, and abnormal 17p In CR2 or CR3 Patients with chemosensitive active disease Myelodysplastic syndrome in high-intermediate (int-2) and high risk categories by International Prognostic Scoring System (IPSS) or revised (R)-IPSS 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) 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) 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) Note: To be performed within 28 days prior to day 1 of protocol therapy 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 Note: To be performed within 28 days prior to day 1 of protocol therapy 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) If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed Meets other institutional and federal requirements for infectious disease titer requirements Note: Infectious disease testing to be performed within 28 days prior to Day 1 of protocol therapy Women of childbearing potential (WOCBP): negative urine or serum pregnancy test If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required 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 Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only) The recipient must have a related donor genotypically human leukocyte antigen (HLA)-A, B,C and DRB1 loci haploidentical to the recipient No HLA matched sibling or matched unrelated donor is available Patients should be off all previous intensive therapy, chemotherapy or radiotherapy for 3 weeks prior to commencing therapy on this study (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.) 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: DONOR: Age =< 60 years of age DONOR: For younger donors, no more than 20 mL bone marrow may be harvested per kg of donor body weight DONOR: Medical history and physical examination confirm good health status as defined by institutional standards 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 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 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 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 DONOR: Selection of a haploidentical donor will require absence of pre-existing donor-directed anti-HLA antibodies in the recipient Exclusion Criteria: Patients should not have any uncontrolled illness including ongoing or active bacterial, viral or fungal infection Patient may not be receiving any other investigational agents or concurrent biological, intensive chemotherapy or radiation therapy for the previous three weeks from conditioning (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.) Herbal medications dependency History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent No intercurrent illness or other malignancy (other than non-melanoma skin cancer) Active infection requiring antibiotics Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection Females only: Pregnant or breastfeeding 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 Patients who had a prior autologous or allogeneic transplant Patients who had prior radiation therapy of more than 20% of bone marrow containing areas or to any area exceeding 2000 cGy Patients with HLA-matched or partially matched (7/8 or 8/8) related or fully matched unrelated donor available to donate Patients who have received more than 3 prior regimens, where the regimen intent was to induce remission Patients with treatment history including anti-CD33 monoclonal antibody therapy (e.g., SGN-CD33 or Mylotarg) 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) DONOR: Evidence of active infection DONOR: Medical or physical reason which makes the donor unlikely to tolerate or cooperate with growth factor therapy and leukapheresis DONOR: Factors which place the donor at increased risk for complications from leukapheresis or granulocyte colony-stimulating factor (G-CSF) therapy DONOR: HIV positive
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Monzr M Al Malki
Organizational Affiliation
City of Hope Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Monzr M. Al Malki
Phone
626-218-2405
Email
malamalki@coh.org
First Name & Middle Initial & Last Name & Degree
Monzr M. Al Malki

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs