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Recurrent Severe Aplastic AnemiaPhase 1NCT05757310

A Reduced-Intensity Conditioning Regimen (Cyclophosphamide, Pentostatin, Anti-thymocyte Globulin) Followed by Haploidentical Hematopoietic Stem Cell Transplant for the Treatment of Patients With Refractory or Recurrent Severe Aplastic Anemia

A Phase 1 study testing Anti-Thymocyte Globulin, Biospecimen Collection and Bone Marrow Aspirate in people with Recurrent Severe Aplastic Anemia and Refractory Severe Aplastic Anemia, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not… Read more about this study

Who is it for?
Ages Up to 75 yearsHealthy volunteers can take part
What is being tested?
Anti-Thymocyte Globulin, Biospecimen Collection and Bone Marrow Aspirate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
15 Nov 2024to 18 Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

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 Up to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • RECIPIENT: Documented informed consent of the participant.
  • RECIPIENT: Age: >= 40 years but =< 75 years of age at time of enrollment.
  • RECIPIENT: Failed at least one trial of immunosuppressive therapy (IST) by being refractory (persistence of severe cytopenia and fulfillment of SAA disease criteria at least 3 months after initial IST) or having relapsed (initial improvement of cytopenia after first-line IST but then a later return to fulfillment of SAA disease criteria when IST is decreased or ceased). IST could have included anti-thymocyte globulin (ATG) based regimens, calcineuPririn inhibitors and/or other higher dose therapy directed at the treatment of primary SAA.
  • RECIPIENT: Karnofsky performance score >= 60%.
  • RECIPIENT: Confirmed diagnosis of severe aplastic anemia as:
  • Bone marrow cellularity < 25% or marrow cellularity < 50% but with < 30% residual hematopoietic cells;
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  • Two out of three of the following (in peripheral blood):
  • Neutrophils < 0.5 x 10^9/L;
  • Platelets < 20 x 10^9/L;
  • Reticulocyte count < 20 x 10^9/L (< 60 x 10^9/L using an automated analysis).
  • RECIPIENT: No suitable fully matched related sibling donor (6/6 match for human leukocyte antigen [HLA]-A and B at intermediate or high resolution and DRbetaA1 at high resolution using deoxyribonucleic acid [DNA]-based typing) available.
  • RECIPIENT: Available relative of the patient who is a haploidentical match, including biological parents, siblings or half siblings, children, uncles/aunts, first cousins, etc. Eligible haploidentical donors will have 2-4 mismatches if HLA-A, -B, -C, and -DRB1 typing is used; 2-5 mismatches if HLA-A, -B, -C, -DRB1, and -DQB1 typing is used; and 2-6 mismatches if HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 typing is used. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must demonstrate that they are a full haplotype match by being identical at a minimum of one allele (at high resolution DNA-based typing) at the following genetic loci: HLA-A, -B, -C, and DRB1 if 8 allele typing is used; HLA-A, -B, -C, -DRB1, and -DQB1 if 10 allele typing is used; and HLA-A, -B, -C, -DRB1-, DQB1, and -DPB1 is 12 allele typing is used by the local center.
  • RECIPIENT: Patient and/or legal guardian must sign informed consent for the hematopoietic stem cell transplantation (HSCT).
  • RECIPIENT: The haplo donor and/or legal guardian must be able to sign informed consent documents.
  • RECIPIENT: The potential haplo donor must be willing and able to donate bone marrow.
  • RECIPIENT: The weight of the haplo donor must be >= 20 kg.
  • RECIPIENT: Total bilirubin < 3.0 x the upper limit of normal (ULN) for age (patients who have been diagnosed with Gilbert's Disease are allowed to exceed this limit)
  • RECIPIENT: Aspartate aminotransferase (AST) =< 5.0 x ULN.
  • RECIPIENT: Alanine transaminase (ALT) =< 5.0 x ULN.
  • RECIPIENT:
  • For patients >= 13.0 years of age at the time of enrollment: Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula.
  • For patients < 13 years of age at enrollment: Glomerular filtration rate (GFR) estimated by the updated Schwartz formula > 90 mL/min/1.73 m^2. If the estimated GFR is < 90 mL/min/1.73m^2, then renal function must be measured by 24-hour creatinine clearance or nuclear GFR, and must be > 50mL/min/1.73m^2.
  • RECIPIENT: 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.
  • RECIPIENT: Echocardiogram (ECHO) or multigated acquisition (MUGA): Left ventricular ejection fraction (LVEF) at rest >= 40%. For patients aged < 13 years, shortening fraction (SF) >= 26% by echocardiogram or MUGA may be substituted for LVEF.
  • RECIPIENT:
  • For patients > 13.0 years of age: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected/adjusted for hemoglobin) > 40% and forced expiratory volume in 1 second (FEV1) > 50% predicted (without administration of bronchodilator) and forced vital capacity (FVC) > 50% predicted.
  • For patients < 13.0 years of age unable to perform pulmonary function tests (PFTs) due to age or developmental ability: (1) no evidence of dyspnea at rest and (2) no need for supplemental oxygen and (3) oxygen (O2) saturation > 92% on room air at sea level (with lower levels allowed at higher elevations per established center standard of care [e.g., Utah, 4,200 feet above sea level, does not give supplemental oxygen unless below 90%]).
  • RECIPIENT: Seronegative for human immunodeficiency virus (HIV) antigen and antibody (Ag/Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])
  • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed.
  • RECIPIENT: Antibodies to donor red blood cell antigens including ABO and rhesus (Rh) meets institutional titer requirements.
  • RECIPIENT: WOCBP or sexually active male: Agreement to use adequate contraception prior to study entry and 6 months post-CD4+ T-cell-depleted-HaploHCT.
  • DONOR: Documented protocol-specific City of Hope (COH) informed consent per local, state and federal guidelines
  • DONOR: Documented general institutional informed consent per local, state and federal guidelines.
  • DONOR: Age: younger than 60 years.
  • DONOR: Haplo donor selection is based on HLA typing and relationship to recipient.
  • DONOR: When more than one donor is available, the donor with the lowest number of HLA allele mismatches will be chosen unless there is HLA cross-match incompatibility or a medical reason to select otherwise. In cases where there is more than one donor with the least degree of mismatch, donors will be selected based on the most favorable combination of HLA compatibility in cross-match testing and ABO compatibility. Prioritization is given to the lowest number of mismatches in the host-versus-graft (HVG) direction to minimize the risk of graft failure.
  • DONOR: If there is more than one donor with the least amount of host-versus-graft (HVG) allele mismatches, the suggested prioritization in order of importance includes ABO compatibility, cytomegalovirus (CMV) status (use a sero-negative donor for a sero-negative recipient or use a sero-positive donor for a sero-positive recipient), younger age and lighter weight (this rule applies down to the age of 18, however, children may also be used as donors if appropriate), and sex of the donor (if all else is equal, males are preferred over nulliparous females over multiparous females).
  • DONOR: Infectious disease screening performed within 30 days prior to stem cell collection and per federal guidelines and is:
  • Seronegative for HIV Ag, HIV 1+2 Ab, human T-lymphotropic virus (HTLV) I/II Ab, hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb) (immunoglobulin M [IgM] and immunoglobulin G [IgG]), HCV Ab;
  • Negative RPR for syphilis.
  • DONOR: WOCBP: Urine pregnancy testing performed within 7 days prior to stem cell mobilization
  • DONOR: Is approved and completed evaluation per institutional guidelines.

Who cannot join

  • RECIPIENT: Inherited and acquired (non-aplastic anemia) bone marrow failure syndromes such as Fanconi anemia must be ruled out according to center standards.
  • RECIPIENT: Clonal cytogenetic abnormalities consistent with pre-myelodysplastic syndrome (pre-MDS) or MDS on marrow examination (e.g. Monosomy 7).
  • RECIPIENT: Any somatic mutations (including TERT, TERC, DKC1, NOP10) other than PIG-A (PNH) or BCOR mutation.
  • RECIPIENT: Diagnosis of myelodysplastic syndrome (MDS).
  • RECIPIENT: Presence of anti-donor HLA antibodies (positive anti-donor HLA antibody is defined as a positive cross-match test of any titer by complement-dependent cytotoxicity or flow cytometric testing or the presence of anti-donor HLA antibody to the high expression loci HLA-A, B, C, DRB1, or DPB1 with mean fluorescence intensity [MFI] > 1000 by solid phase immunoassay).
  • RECIPIENT: Prior allogeneic stem cell transplant.
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  • RECIPIENT: Prior solid organ transplant.
  • RECIPIENT: Known life-threatening reaction (i.e., anaphylaxis) to Thymoglobulin (registered trademark) that would prohibit use for the patient as this study requires use of the Thymoglobulin (registered trademark) preparation of ATG.
  • RECIPIENT: Uncontrolled bacterial, viral, or fungal infection at the time of enrollment. Uncontrolled is defined as currently taking medication and with progression or no clinical improvement on adequate medical treatment.
  • RECIPIENT: Seropositive for the human immunodeficiency virus (HIV).
  • RECIPIENT: Active hepatitis B or C determined by a detectable viral load of HBV or HCV.
  • RECIPIENT: Female patients who are pregnant (per institutional practice) or breast-feeding.
  • RECIPIENT: Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent > 5 years previously will be allowed. Cancer treated with curative intent =< 5 years previously will not be allowed unless approved by the protocol chairs and/or protocol officer.
  • RECIPIENT: Alemtuzumab or ATG within 2 weeks of enrollment.
  • RECIPIENT: 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.
  • RECIPIENT: 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: Has undergone any transplantation (i.e. organ, stem cell, bone marrow, blood).
  • DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy.
  • DONOR: 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: WOCBP: pregnant or =< 6 months breastfeeding.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Ryotaro Nakamura, 626-641-1851 ext. 82405, rnakamura@coh.org

    Ryotaro Nakamura

    Recruiting

Other trials in United States

About this study

Official title: A Pilot Study to Evaluate the Safety and Feasibility of Induction of Mixed Chimerism in Severe Aplastic Anemia Patients With COH-MC-17: A Non-Myeloablative/ Reduced-Intensity, Conditioning Regimen and CD4+ T-Cell-Depleted Haploidentical Hematopoietic Transplant

This phase I trial evaluates the safety and feasibility of using a reduced-intensity regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin prior to a CD4+ T-cell depleted haploidentical hematopoietic cell transplant (haploHCT) for the treatment of patients with severe aplastic anemia that does not respond to treatment (refractory) or that has come back (recurrent). Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid. It may also lower the body's immune response. Pentostatin blocks a protein needed for cell growth. Anti-thymocyte globulin is an immunosuppressive drug can destroy immune cells known as T-cells. HaploHCT transfers blood-forming stem cells from a healthy partially-matched donor to a patient. Administering a regimen of cyclophosphamide, pentostatin, and anti-thymocyte globulin before haploHCT may help make room for the new, healthy cells and may reduce the risk of graft versus host disease.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if the infusion of CD4+ T-cell-depleted hematopoietic cells from a haploidentical donor, following a non-myeloablative/ reduced-intensity preparative regimen is safe in patients with severe aplastic anemia (SAA).

II. To determine the feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product, as assessed by:

IIa. Ability to meet the minimum required CD34+ cell dose, and; IIb. Ability to meet the CD4+ T-cell depletion product release requirements.

SECONDARY OBJECTIVES:

  1. To evaluate toxicities including type, frequency, severity, attribution, time course, and duration. (Safety/tolerability) II. To summarize and evaluate hematologic (neutrophil and platelet) recovery, including marrow failure. (Safety/tolerability) III. To estimate the incidence of infection and infectious disease related complications at 100 days. (Safety/tolerability) IV. To estimate the incidence of SAA related complications. (Safety/tolerability) V. To estimate the cumulative incidence of non-relapse mortality at 100-days, 1-year and 2-years post hematopoietic stem-cell transplantation (HCT). (Safety/tolerability) VI. To estimate the cumulative incidence of acute graft versus host disease (GvHD) (grades: II-IV, III-IV) at 100-days and chronic GvHD (grades: any, moderate-severe) at 6-months, 1-year and 2-years post HCT. (Safety/tolerability) VII. To estimate the overall survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) VIII. To estimate the disease-free survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) IX. To estimate the event-free survival probability at 100-days, 1-year and 2-years post HCT. (Survival/relapse) X. To estimate the cumulative incidence of disease relapse at 100-days, 1-year and 2-years post HCT. (Survival/relapse) XI. To describe response as categorized by graft failure, persistent post-immunosuppressant (IS) mixed chimerism, persistent IS-dependent mixed chimerism, complete chimerism. (Chimerism) XII. To summarize/characterize patient chimerism (percent of donor total nucleated and donor lineage specific cells) over time. (Kinetics)

EXPLORATORY OBJECTIVES:

  1. To describe the ratio of donor to recipient de novo thymic T cells over the course of 2 years within the peripheral blood compartment.

II. To describe the ratio of donor to recipient regulatory T cells and regulatory B cells over the course of 2 years within the peripheral blood and bone marrow compartments.

III. To describe the tolerance status of donor and host-type T cells over the course of 2 years within the peripheral blood compartment.

IV. To describe the T-cell repertoire of donor- and host-type T cells over the course of 2 years within the peripheral blood compartment.

  1. To describe the bone marrow niche and peripheral blood cytokine profile over time.

VI. To describe bone marrow progenitor chimerism over time.

OUTLINE:

Patients receive cyclophosphamide orally (PO) and intravenously (IV), pentostatin IV, anti-thymocyte globulin IV and undergo CD4+ T-cell depleted haploHCT on study. Patients also undergo bone marrow aspirate, bone marrow biopsy, and collection of blood samples at screening and follow-up.

Being tested
Anti-Thymocyte Globulin, Biospecimen Collection, Bone Marrow Aspirate, Bone Marrow Biopsy, Cyclophosphamide
Medical subject headings
Anemia, Aplastic

What participants receive

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

  • Anti-Thymocyte GlobulinBiological

    Also called Antithymocyte Globulin, Antithymocyte Serum, ATG, ATS

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirateProcedure or surgery

    Also called Human Bone Marrow Aspirate

    Undergo bone marrow aspirate

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given PO and IV

  • Haploidentical Hematopoietic Cell TransplantationProcedure or surgery

    Also called Haploidentical Stem Cell Transplantation, HLA-Haploidentical Hematopoietic Cell Transplantation, Stem Cell Transplantation, Haploidentical

    Undergo CD4+ T-cell depleted haploHCT

  • PentostatinDrug

    Also called (R)-3-(2-Deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7, 8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol, 2'-Deoxycoformycin, CI-825, Co-Vidarabine

    Given IV

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05757310
Study groupRoleWhat they receive
Treatment (conditioning, haploHCT)ExperimentalPatients receive cyclophosphamide PO and IV, pentostatin IV, anti-thymocyte globulin IV and undergo CD4+ T-cell depleted haploHCT on study. Patients also undergo bone marrow aspirate, bone marrow biopsy, and collection of blood samples at screening and follow-up.
Receives: Biological: Anti-Thymocyte Globulin; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspirate; Procedure: Bone Marrow Biopsy; Drug: Cyclophosphamide; Procedure: Haploidentical Hematopoietic Cell Transplantation; Drug: Pentostatin; Other: Questionnaire Administration

What is being measured

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

  1. Incidence of adverse events

    Toxicity will be graded according to the National Cancer Institute's-Common Terminology Criteria for Adverse Events version 5.0. Graft versus host disease (GVHD) specific toxicities will be defined per 1994 Keystone Consensus Criteria. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study regimen and reversibility or outcome. This will include infectious disease related complications and autoimmune disease related complications. Cumulative incidence curves will be used for time to event variables with competing risks events such as acute GVHD or chronic GVHD. Point estimates and 90% confidence intervals will be used.

    Measured: From day -22 to day +100 or occurrence of unacceptable toxicity, whichever occurs first

  2. Ability to meet CD4+ T-cell depleted product release requirements (feasibility)

    The feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product will be assessed by the ability to meet product release requirements. Product release requirements include the following: (1) CD34+ cells: Post-processing CD34+ cell target of 7.5-13.0 x 106 cells/kg of recipient body weight; (2) CD4+ T-cell depletion: >= 97% of CD4+ T-cells in the the hematopoietic cell product for manufacturing; (3) Sterility (e.g. endotoxin and gram staining). Descriptive statistics will be used to characterize feasibility.

    Measured: Up to 3 years

  3. Ability to meet minimum required cell dose (feasibility)

    The feasibility of producing an infusion ready CD4+ T-cell-depleted hematopoietic product will be assessed by the ability to meet minimum required cell doses. This outcome will be evaluated using the following: (1) CD34+ collected (per day of apheresis); (2) CD34+ recovery: % CD34+ cells recovered from the CD34+ cell number in the product being manufactured (pre-CD4+ T cell depletion); (3) Cell dose: pooled and back up product; (4) Cell dose adequate given recipient's body weight plus the required pre-processed back-up set aside (yes/no); (5) Number (median, range) of apheresis; (6) % CD4+ T-cell depletion; (7) reason for not meeting product release requirements. Descriptive statistics will be used to characterize feasibility.

    Measured: Up to 3 years

Secondary outcomes (14)

  1. Incidence of adverse events of grade 3 or higher

    Measured: Up to 3 years

  2. Incidence of infection

    Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any.

    Measured: Up to 3 years

  3. Time to neutrophil recovery

    Measured: From the date of CD4+ T-cell-depleted product infusion to the first of three consecutive days of absolute neutrophil count (ANC) >= 500/mm^3 and ANC >= 1000/mm^3, assessed up to 3 years

  4. Time to platelet recovery

    Measured: Time to the first day of the first of three consecutive laboratory values when the platelet count is >= 20,000/mm^3 and 100,000/mm^3 without a platelet transfusion in the previous seven, assessed up to 3 years

  5. Marrow failure

    Defined as primary graft failure: failure to achieve a sustained neutrophil count of >= 500/ mm^3 in the absence of disease relapse by 28 days or secondary graft failure: a decline in the neutrophil count to less than 500/ mm^3 after initial engraftment, which was unrelated to infection, medications, or disease relapse.

    Measured: Up to 28 days post transplant for primary graft failure or after initial engraftment for secondary graft failure, assessed up to 3 years

  6. Cumulative incidence of non-relapse mortality (NRM)

    NRM is defined as death occurring in a patient from causes other than disease relapse; relapse is a competing event. Cumulative incidence curves will be used for time to event variables with competing risks events. Point estimates and 90% confidence intervals will be used.

    Measured: From enrollment until non-disease related death or last follow up and from date of CD4+ T-cell-depleted product infusion, assessed up to 3 years

  7. Cumulative incidence of acute GvHD (II-IV and III-IV)

    Acute GvHD is graded according to the Keystone Consensus Criteria. The first day of acute GvHD onset at a certain grade will be used to calculate cumulative incidence curves; death is a competing event. Cumulative incidence curves will be used for time to event variables with competing risks events. Point estimates and 90% confidence intervals will be used.

    Measured: From day 0 through day +100 post-transplant

  8. Cumulative incidence of chronic GvHD (any and moderate-severe)

    Chronic GvHD is graded according to the 2014 NIH Consensus Criteria. The first day of chronic GvHD onset at a certain grade will be used to calculate cumulative incidence curves; disease recurrence or death is a competing event. Cumulative incidence curves will be used for time to event variables with competing risks events. Point estimates and 90% confidence intervals will be used.

    Measured: From day +100 to +2 years post-transplant

  9. Overall survival

    Patients are considered a failure for this endpoint if they die, regardless of cause of death. Overall survival will be censored at last follow-up if patients are known to be alive. Kaplan-Meier curves will be used for time to event variables.

    Measured: Time from enrollment to death, assessed up to 3 years

  10. Cumulative incidence of relapse

    Disease relapse is defined as a decline in the neutrophil count to less than 500/ mm^3 after initial engraftment, which was unrelated to infection, medications, or other causes. Death without disease recurrence will be a competing risk event. Time to disease recurrence will be censored at the last disease assessment of patients remain alive and free of disease recurrence.

    Measured: Time from enrollment/infusion of depleted hematopoietic product to first observation of disease relapse, assessed up to 3 years

  11. Disease-free survival (DFS)

    Patients are considered a failure for this endpoint if they relapse or die, regardless of cause of death. DFS will be censored at last follow-up if patients are alive and free of disease. Kaplan-Meier curves will be used for time to event variables.

    Measured: Time from enrollment/ infusion of CD4+ T-cell-depleted hematopoietic product to relapse, therapy for hemoglobinopathy, death from any cause, assessed up to 3 years

  12. Event-free survival (EFS)

    EFS will be censored at last follow-up if patients are free of any above-mentioned events. Kaplan-Meier curves will be used for time to event variables.

    Measured: Time from enrollment/infusion of CD4+ T-cell product to any of the following events (whichever occurs first): therapy for hemoglobinopathy, primary/secondary graft failure, acute GvHD, chronic GvHD, death from any cause, assessed up to 3 years

  13. Chimerism

    Persistent IS-dependent mixed chimerism: Between 10% and 94% donor chimerism at two years post-transplant and on IS. Complete chimerism: >94% donor chimerism at two years post-transplant. Primary donor graft failure: Defined as < 10 % donor chimerism by day +30 post-transplant.. Secondary donor graft failure: Defined as < 10 % donor chimerism beyond day +30 in patients with prior documentation of >= 10% donor cells by day +30. Failure is based on two separate measurements obtained at least 2 weeks apart. Line charts or scatterplots will be used for changes of endpoints over time such as chimerism.

    Measured: Up to 2 years

  14. Kinetics

    Will evaluate T-cells: CD3, CD4, CD8, B-cells: CD19, natural killer cells: CD56, monocytes: CD14, granulocytes: CD15, total nucleated cells. Line charts or scatterplots will be used for changes of endpoints over time.

    Measured: At 7, 15, 30, 60, 100, 180 days and 1, 1.5, and 2 years post-transplant

Timeline

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

  1. First posted7 Mar 2023
  2. Study start15 Nov 2024
  3. Primary completion18 Jun 2027 (estimated)
  4. Study completion18 Jun 2027 (estimated)

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05757310
Sponsor's protocol ID
23139
Other IDs
NCI-2022-10251, 23139, P30CA033572
Status last verified
Dec 2025
First submitted
10 Jan 2023
Last updated
5 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-Thymocyte Globulin, Biospecimen Collection and Bone Marrow Aspirate in people with Recurrent Severe Aplastic Anemia and Refractory Severe Aplastic Anemia, run by City of Hope 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 42 inclusion and 22 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: looking for participants now, as of the sponsor's last update on 5 Jan 2026. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: From day -22 to day +100 or occurrence of unacceptable toxicity, whichever occurs first). The study lists 3 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 NCT05757310.

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 5 Jan 2026.

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