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Acute Lymphoblastic LeukemiaPhase 2NCT05364762

Adding Itacitinib to Cyclophosphamide and Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplants

A Phase 2 study testing Cyclophosphamide, Itacitinib and Peripheral Blood Stem Cell Transplantation in people with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Read more about this study

Who is it for?
Ages Up to 80 years
What is being tested?
Cyclophosphamide, Itacitinib and Peripheral Blood Stem Cell Transplantation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
29 Dec 2022to 25 Mar 2027
Phase
Phase 2

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 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • Assent, when appropriate, will be obtained per institutional guidelines
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Age: =< 80 years
  • Note: Patients > 70 years of age must have Karnofsky performance status >= 80 and HCT-comorbidity index (CI) =< 2
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  • Karnofsky performance status >= 70%
  • Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing)
  • Acute leukemias (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) in complete remission with bone marrow (BM) blast of < 5%
  • Myelofibrosis (MF): Primary or secondary with high- or intermediate-2 risk per Dynamic International Prognostic Scoring System (DIPSS)
  • Myelodysplastic syndrome (blast < 10%)
  • Myeloproliferative neoplasm (MPN) other than MF needing HCT
  • Chronic myelomonocytic leukemia (CMML)
  • Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) < 5 x ULN (within 30 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 (within 30 days prior to day 1 of protocol therapy unless otherwise stated)
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Note: To be performed within 30 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 diffusion capacity of the lungs for carbon monoxide (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin) (within 30 days prior to day 1 of protocol therapy)
  • If unable to perform pulmonary function tests: O2 saturation > 92% on room air (within 30 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) (within 30 days prior to day 1 of protocol therapy)
  • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed OR
  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • 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 (within 30 days prior to day 1 of protocol therapy)
  • 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)

Who cannot join

  • Prior allogeneic HCT
  • Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days prior to day 1 of protocol therapy
  • Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy is not considered as an exclusion criterion. Patients on maintenance chemotherapy are not excluded
  • Other investigational drugs for treatment of GVHD
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
  • Psychological issues, no appropriate caregivers identified, or non-compliant to medication
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  • Clinically significant uncontrolled illness
  • Uncontrolled infection (bacterial, viral, fungal)
  • Other active malignancy
  • 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
  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Single Center Pilot Study to Investigate the Efficacy of Adding Itacitinib to Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis After Reduced Intensity Conditioning Matched Donor Hematopoietic Cell Transplantation With Peripheral Blood Stem Cells as Graft Source

This clinical trial evaluates the safety and effectiveness of adding itacitinib to cyclophosphamide and tacrolimus for the prevention of graft versus host disease (GVHD) in patients undergoing hematopoietic stem cell transplant. Itacitinib is an enzyme inhibitor that may regulate the development, proliferation, and activation of immune cells important for GVHD development. Cyclophosphamide and tacrolimus are immunosuppressive agents that may prevent GVHD in patients who receive stem cell transplants. Giving itacitinib in addition to cyclophosphamide and tacrolimus may be more effective at preventing GVHD in patients receiving hematopoietic stem cell transplants.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Safety lead-in: Determine if shortening tacrolimus administration period to 60 days (day +65 post-hematopoietic cell transplantation [HCT]), when combined with post-transplant cyclophosphamide (PTCy) and itacitinib at a fixed dose level as graft-versus-host disease (GVHD) prophylaxis, is safe and effective after mobilized peripheral blood stem cell (PBSC) allogeneic hematopoietic cell transplantation (HCT) from a matched related/unrelated donor, as assessed by grade 3-4 GVHD as dose limiting toxicity.

II. Following the safety lead-in, evaluate the efficacy of PTCy, itacitinib and tacrolimus GVHD prophylaxis, as assessed by 1-year GVHD-free relapse-free survival (GRFS).

SECONDARY OBJECTIVES:

  1. Evaluate the safety of this regimen by assessing:

Ia. Adverse events: type, frequency, severity, attribution, time course, duration.

Ib. Complications including acute and chronic GVHD, infections and delayed engraftment.

II. Estimate overall survival (OS), progression-free survival (PFS), cumulative incidences of relapse/disease progression, and non-relapse mortality (NRM) at 100 days, and 1-year post-transplant.

III. Estimate rates of acute and chronic GvHD, infections, and neutrophil recovery.

EXPLORATORY OBJECTIVES:

  1. Donor cell engraftment will be assessed by count monitoring and short tandem repeat (STR) chimerism analysis on days +30 and day +100.

II. Describe the kinetics of immune cell recovery. III. Evaluate patient's quality of life on day +100, 6 months and one-year post-HCT.

IV. Pharmacokinetics: serial blood sampling will be done to evaluate the steady-state pharmacokinetics of itacitinib after PTCy.

  1. Describe the kinetics of GVHD biomarkers, JAK-related inflammatory cytokines and STAT phosphorylation.

VI. Evaluate and describe the cytokine release syndrome (CRS) post-HCT by assessing the incidence, frequency, and severity of CRS.

VII. Obtain a preliminary estimate of gut microbiome diversity at baseline (preferably before fludarabine administration), and then on days +14, +30, and +100.

OUTLINE:

Patients undergo peripheral blood stem cell infusion on day 0. Patients receive cyclophosphamide intravenously (IV) once daily (QD) on days 3 and 4, itacitinib orally (PO) QD on days 5-100, and tacrolimus IV or PO on days 6-65.

After completion of study treatment, patients are followed up at day 180 and 1 year.

Being tested
Cyclophosphamide, Itacitinib, Peripheral Blood Stem Cell Transplantation, Quality-of-Life Assessment, Tacrolimus
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Myeloproliferative Disorders, Primary Myelofibrosis

What participants receive

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

  • CyclophosphamideDrug

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

    Given IV

  • ItacitinibDrug

    Also called INCB 039110, INCB-039110, INCB039110

    Given PO

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood, Peripheral Blood Progenitor Cell Transplantation

    Undergo peripheral blood stem cell infusion

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

Study groups in NCT05364762
Study groupRoleWhat they receive
Prevention (PBSCs, cyclophosphamide, itacitinib, tacrolimus)ExperimentalPatients undergo peripheral blood stem cell infusion on day 0. Patients receive cyclophosphamide IV QD on days 3 and 4, itacitinib PO QD on days 5-100, and tacrolimus IV or PO on days 6-65.
Receives: Drug: Cyclophosphamide; Drug: Itacitinib; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Drug: Tacrolimus

What is being measured

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

  1. Number of participants with Grade III-IV acute graft versus host disease (GVHD)

    Acute GVHD will be graded and staged according to Mount Sinai Acute GVHD International Consortium (MAGIC) criteria.

    Measured: By day 100

  2. GVHD-free relapse-free survival rate

    Will be calculated using the Kaplan-Meier method.

    Measured: From start of hematopoietic cell transplantation to grade III-IV acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed at 1 year

Secondary outcomes (19)

  1. Incidence of adverse events

    The toxicity/adverse event information recorded on each subject will include type, severity, duration, and attribution/ association with the study regimen. Tables will be constructed to summarize the observed incidence, severity and type of toxicity, including infection.

    Measured: Up to 2 years

  2. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: Day of stem cell infusion (day 0) until death or last follow-up, assessed at 100 days

  3. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: Day of stem cell infusion (day 0) until death or last follow-up, assessed at 180 days

  4. Overall survival

    Will be calculated using the Kaplan-Meier method.

    Measured: Day of stem cell infusion (day 0) until death or last follow-up, assessed at 1 year

  5. Progression free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 100 days

  6. Progression free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 180 days

  7. Progression free survival

    Will be calculated using the Kaplan-Meier method.

    Measured: From the date of stem cell infusion to the date of death, disease relapse/progression, or last follow-up, assessed at 1 year

  8. Relapse/progression

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 to relapse/progression, assessed at 100 days

  9. Relapse/progression

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 to relapse/progression, assessed at 180 days

  10. Relapse/progression

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 to relapse/progression, assessed at 1 year

  11. Non-relapse mortality

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 until non-disease related death or last follow-up, assessed at 100 days

  12. Non-relapse mortality

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 until non-disease related death or last follow-up, assessed at 180 days

  13. Non-relapse mortality

    The cumulative incidence will be calculated using the competing risk method.

    Measured: Day 0 until non-disease related death or last follow-up, assessed at 1 year

  14. Rate of acute GVHD

    Acute GVHD will be graded and staged according to MAGIC criteria. The first day of acute GVHD onset at a certain grade will be used to calculate the cumulative incidence (grades II-IV). The endpoint will be evaluated from day 0 through 100 days post-transplant. The cumulative incidence will be calculated using the competing risk method.

    Measured: On day 100

  15. Rate of chronic GVHD

    Chronic graft versus host disease will be evaluated and scored according to National Institutes of Health Consensus Staging. The first day of chronic GVHD onset will be used to calculate the cumulative incidence. The cumulative incidence will be calculated using the competing risk method.

    Measured: From day 80 through 1 year post-transplant

  16. Rate of infection

    Microbiologically documented infections will be reported by site of disease, date of onset, severity and resolution, if any. This data will be captured via case report form and will be collected from day -7 to day 120 post-transplant and will follow the same data collection intervals as the toxicity and adverse event data.

    Measured: Day -7 to day 120

  17. Rate of hematologic recovery

    Absolute neutrophil count >= 0.5 x 10^3/uL achieved and sustained for 3 consecutive lab values on different days with no subsequent decline.

    Platelets >= 20 K/uL independent of platelet transfusion support (date should reflect no transfusions in previous 7 days, and the first of 3 consecutive lab values on different days).

    Measured: Up to 2 years

  18. Incidence of cytokine release syndrome

    Defined and graded per American Society for Transplantation and Cellular Therapy criteria.

    Measured: Up to 2 years

  19. Gut microbiome assessment

    Gut microbiome diversity will be assessed by the inverse Simpson Index and compared among CBM588-treated/untreated patients; the inverse Simpson index is an ecological measure of α microbial diversity calculated by the inverse of the expected probability of 2 randomly selected bacterial sequences as belonging to the same operational taxonomic unit.

    Measured: Up to 2 years

Timeline

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

  1. First posted6 May 2022
  2. Study start29 Dec 2022
  3. Primary completion25 Mar 2027 (estimated)
  4. Study completion25 Mar 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 2
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05364762
Sponsor's protocol ID
21776
Other IDs
NCI-2022-03765, 21776, P30CA033572
Status last verified
Oct 2026
First submitted
3 May 2022
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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