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Secondary MyelofibrosisPhase 1NCT03118492

Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Patients With Secondary Myelofibrosis

A Phase 1 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine in people with Secondary Myelofibrosis, 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 pilot phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating patients with secondary myelofibrosis. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Secondary Myelofibrosis
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
1 siteUnited States
Study dates
21 Jun 2017to 29 Apr 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 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of primary of secondary myelofibrosis with transplant indication by Dynamic International Prognostic Scoring System (DIPSS)-plus (> intermediate-1)
  • Patients >= age 50 must have a comorbidity score (hematopoietic cell transplant-comorbidity index [HCT-CI]) < 4 (Sorror)
  • Patients can be in chronic phase (CP) with bone marrow (BM) blast count =< 15% as long as no evidence of disease acceleration per principal investigator (PI) and treating physician's opinion or after progression to acute myeloid leukemia (AML) and achieved =< 5% BM blasts (morphologic complete remission [CR] prior to transplant)
  • Lack of an human leukocyte antigen (HLA) matched donor or need to proceed fast to transplantation when a patient does not have an immediately available matched unrelated donor (typed by high-resolution in the registry)
  • Performance status >= 70% (Karnofsky); patients > 50 years should have adequate cognitive function; any concerns regarding cognitive function should be addressed by a geriatrician/neurologist
  • Alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin =< 5 X upper limit of normal (ULN)
Show all 21Show fewer
  • Measured creatinine clearance > 60 mls/min
  • Left ventricular ejection fraction (LVEF) >= 50%
  • Corrected carbon monoxide diffusing capability (DLCOc) >= 50%
  • No active infections
  • Prior treatment with JAK2 inhibitor therapy is not excluded; a JAK2 inhibitor will need to be stopped 1-2 days prior to starting conditioning regimen
  • DONOR: Documented informed consent per local, state and federal guidelines
  • DONOR: Genotypically haploidentical as determined by HLA typing
  • Preferably a non-maternal 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, children, or cousins in rare instances
  • DONOR: Absence of pre-existing donor-specific anti-HLA antibodies (DSA) in the recipient; Patients with pre-existing DSA could undergo desensitization per City of Hope (COH) standard operating procedures [SOP] and should have DSA < MFI of 2000 prior to conditioning at discretion of PI
  • DONOR: Infectious disease screening performed within 30 days prior to stem cell mobilization per federal guidelines and is:
  • Seronegative for HIV 1+2 antibody (Ab) and/or HIV polymerase chain reaction (PCR), human T-cell leukemia virus (HTLV) I/II Ab, hepatitis B virus surface antigen (HBsAg), hepatitis B virus surface antibody (HBcAb), hepatitis C virus (HCV) Ab
  • Negative rapid plasma reagin (RPR) for syphilis
  • DONOR: Women of childbearing potential (WOCBP): Urine pregnancy testing performed within 7 days prior to stem cell mobilization
  • DONOR: Is approved and completed evaluation prior to recipient initiation of the preparative regimen per institutional guidelines

Who cannot join

  • Evidence of severe portal hypertension with evidence of decompensation either with bleeding varices, large volume ascites, or hepatic encephalopathy
  • In a bone marrow biopsy 4 weeks prior to start of conditioning on study:
  • > 15% bone marrow blasts at transplant if no history of AML and per PI and treating physician's opinion of disease acceleration
  • > 5% if had previous progression to AML
  • Human immunodeficiency virus (HIV) positive; active hepatitis B or C
  • Patients with active infections; the PI is the final arbiter of the eligibility
Show all 20Show fewer
  • Patients with evidence of severe pulmonary hypertension by echocardiogram and confirmed by a subsequent right side cardiac catheterization pre-enrollment
  • Liver cirrhosis
  • Prior central nervous system (CNS) involvement by tumor cells
  • History of another primary malignancy that has not been in remission for at least 3 years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on papanicolaou [PAP] smear)
  • Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
  • Noncompliance - inability or unwillingness to comply with medical recommendations regarding therapy or follow-up, including smoking tobacco
  • DONOR: Has undergone solid organ, stem cell, bone marrow or blood transplantation
  • DONOR: Receiving any investigational agents, or concurrent biological, chemotherapy, immunosuppression or radiation therapy
  • DONOR: Active infection
  • DONOR: Thrombocytopenia < 150,000 cells /mm^3 at baseline evaluation
  • DONOR: Sero-positive for HIV-1 \& 2 antibody, HTLV-I \& II antibody, hepatitis B virus (HBV) and HCV
  • 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 G-CSF therapy
  • DONOR: WOCBP: Pregnant or =< 6 months breastfeeding

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: A Pilot Study of Reduced Intensity HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Advanced Myelofibrosis

This pilot phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating patients with secondary myelofibrosis. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving combination chemotherapy and total body irradiation before a donor blood stem cell transplant helps to stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the safety and tolerability of reduced-intensity (fludarabine/melphalan) haploidentical hematopoietic cell transplantation (Haplo-HCT) followed by post-transplant cyclophosphamide (PTCy) in patients with advanced myelofibrosis (MF), as assessed by the evaluation of toxicities, including type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

  1. To summarize and evaluate hematologic (neutrophil and platelet) recovery. II. To evaluate and describe cytokine release syndrome (CRS) post haploidentical HCT in the setting of advanced myelofibrosis, as assessed by grade, frequency, severity, duration and reversibility (outcome).

III. To estimate graft failure-free survival (GFS) at 100-days post-transplant. IV. To estimate overall survival (OS), progression-free survival (PFS) and cumulative incidence (CI) of relapse/progression, and non-relapse mortality (NRM) at 100-days, 1-year, and 2-year post transplant.

  1. To estimate the cumulative incidence of acute graft-versus-host disease (GvHD), grade II-IV, at 100-days post-transplant (per Keystone Consensus modification of the Glucksberg criteria).

VI. To estimate the cumulative incidence of chronic GvHD at 1-year and 2-year post transplant (per National Institutes of Health [NIH] Consensus Criteria).

VII. To characterize the severity and extent of acute and chronic GvHD.

EXPLORATORY OBJECTIVE:

  1. To conduct correlative studies and describe inflammatory cytokine levels and GVHD biomarker levels in plasma and T cell differentiation/functions in patients enrolled onto the trial.

OUTLINE:

Patients receive melphalan intravenously (IV) over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo total body irradiation (TBI) on day -1 and hematopoietic cell transplantation (HCT) on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then orally (PO) for 6 months followed by a taper, mycophenolate mofetil PO thrice daily (TID) until day 35, and glycosylated recombinant human G-CSF AVI-014 (G-CSF) IV daily until absolute neutrophil count > 1,500/mm^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed for up to 2 years.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Fludarabine, Glycosylated Recombinant Human G-CSF AVI-014, Laboratory Biomarker Analysis

What participants receive

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

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT

    Undergo HCT

  • CyclophosphamideDrug

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

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Glycosylated Recombinant Human G-CSF AVI-014Biological

    Also called AVI-014

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • Mycophenolate MofetilDrug

    Also called CellCept, MMF

    Given PO

  • TacrolimusDrug

    Also called FK 506, Fujimycin, Hecoria, Prograf

    Given IV or PO

  • Total-Body IrradiationRadiation

    Also called TBI, Total Body Irradiation, Whole Body Irradiation, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT03118492
Study groupRoleWhat they receive
Treatment (combination chemotherapy, TBI, HCT)ExperimentalPatients receive melphalan IV over 30 minutes on day -5, fludarabine IV over 30-60 minutes on days -5 to -2. Patients undergo TBI on day -1 and HCT on day 0. Patients receive cyclophosphamide IV over 1-2 hours on days 3 and 4. Starting on day 5, patients receive tacrolimus IV then PO for 6 months followed by a taper, mycophenolate mofetil PO TID until day 35, and G-CSF IV daily until absolute neutrophil count > 1,500/mm^3 for 3 consecutive days. Treatment continues in the absence of disease progression or unexpected toxicity.
Receives: Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Glycosylated Recombinant Human G-CSF AVI-014; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Drug: Mycophenolate Mofetil; Drug: Tacrolimus; Radiation: Total-Body Irradiation

What is being measured

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

  1. Incidence of adverse events

    Assessed by Bearman Toxicity Scale and National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version (CTCAE) 4.03. 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.

    Measured: Up to 100 days post-hematopoietic cell transplantation (HCT)

  2. Incidence of unacceptable toxicity

    Assessed by Bearman Toxicity Scale and NCI CTCAE version 4.03. 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.

    Measured: Up to 2 years

Secondary outcomes (10)

  1. Neutrophil recovery

    Defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count of >= 500/uL after conditioning.

    Measured: Up to 2 years

  2. Platelet recovery

    Defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count >= 20,000/uL and did not receive a platelet transfusion in the previous 7 days.

    Measured: Up to 2 years

  3. Incidence of cytokine release syndrome (CRS)

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

    Measured: After haploidentical HCT, assessed up to 2 years

  4. Graft failure-free survival

    Will be calculated using Kaplan-Meier product-limit method, 95% confidence intervals will be calculated.

    Measured: Time from start of protocol treatment/infusion of stem cell product to graft-failure, death (from any cause), or last contact, whichever occurs first, assessed up to 2 years

  5. Overall survival

    Will be calculated using Kaplan-Meier product-limit method, 95% confidence intervals will be calculated.

    Measured: Time from start of protocol treatment/infusion of stem cell product to death (from any cause), or last contact, whichever occurs first, assessed up to 36 months

  6. Progression-free survival

    Will be calculated using Kaplan-Meier product-limit method, 95% confidence intervals will be calculated.

    Measured: Time from start of protocol treatment/infusion of stem cell product to, relapse, progression, death (from any cause), or last contact, whichever occurs first, assessed up to 2 years

  7. Cumulative incidence of relapse/progression

    The cumulative incidence of relapse/progression will be estimated using the method described by Gooley et al. (1999).

    Measured: Up to 2 years

  8. Non-relapse mortality (NRM)

    The cumulative incidence of NRM will be estimated using the method described by Gooley et al. (1999).

    Measured: Up to 2 years

  9. Cumulative incidence of acute graft versus host disease (GvHD)

    Assessed by Keystone Consensus criteria. Time to the first day of acute GvHD onset (of any grade) will be used to estimate the cumulative incidence.

    Measured: Up to day 100 post-HCT

  10. Cumulative incidence of chronic graft versus host disease GvHD

    Assessed by National Institutes of Health Consensus Criteria. Time to the first day of chronic GvHD onset (of any grade) will be used to estimate the cumulative incidence.

    Measured: Up to 2 years post-HCT

Timeline

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

  1. First posted18 Apr 2017
  2. Study start21 Jun 2017
  3. Primary completion29 Apr 2027 (estimated)
  4. Study completion29 Apr 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
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03118492
Sponsor's protocol ID
16420
Other IDs
NCI-2017-00613, 16420, P30CA033572
Status last verified
Aug 2026
First submitted
13 Apr 2017
Last updated
21 Aug 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 Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine in people with Secondary Myelofibrosis, 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 21 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 21 Aug 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Up to 100 days post-hematopoietic cell transplantation (HCT)). The study lists 2 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 NCT03118492.

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 21 Aug 2026.

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