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Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 2NCT03333486

Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer

A Phase 2 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Leukemia in Remission, run by Roswell Park Cancer Institute at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, work in different ways to stop the growth of cancer cells… Read more about this study

Who is it for?
Ages 1 year to 75 years
What is being tested?
Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
1 siteUnited States
Study dates
7 Dec 2017to 28 Aug 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 1 year to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Any disease that is considered transplant eligible per TCT standards
  • Disease response noted (i.e. CR, non-CR, or not applicable): Assessed as per disease specific criteria
  • Suitable related haploidentical donor identified per transplant service:
  • Recipient should not have HLA antibodies to potential donor. If the recipient does have HLA antibodies to the potential donor, an alternative donor is preferred; however, if there are no suitable alternative donors, the anti-HLAt antibodies should be depleted per transplant service guidelines.
  • Haploidentical donors that are ABO compatible with the recipient are preferred. Minor ABO incompatibility is preferred to major ABO incompatibility. Major ABO incompatibility between recipient and donor is the least preferred but still acceptable for this study.
  • It is preferred that the haploidentical donor must be available to donate on day -1 and day 0, so that fresh product can be processed by the Stem Cell lab and administered to the patient on day 0.While less preferable, cryopreserved product may be utilized with this product.
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  • Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
  • Left ventricular ejection fraction > 40%
  • Bilirubin, liver alkaline phosphatase, serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
  • Calculated creatinine clearance > 40 cc/min by the modified Cockcroft-Gault formula for adults or the Schwartz formula for pediatrics
  • Have a Karnofsky (adult) or Lansky (for =< 16 years) performance status >= 60%
  • Patient must be able to pass radiation evaluation (i.e.: able to receive 200 cGy)
  • Patients who have failed a prior autologous transplant are eligible; however, at least 90 days must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous BMT
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant must understand the investigational nature of this study and sign an independent ethics committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure
  • If patient is planned to use a fully matched donor, patient is excluded from trial; patient must be planned to undergo a haploidentical matched transplant to participate on study. Patient is still eligible for trial regardless of donor options if PI feels that haplo transplant is in the patient's best interest per clinical decision

Who cannot join

  • Participants who have had chemotherapy (not including molecularly targeted agents; examples include, but are not limited to, tyrosine kinase inhibitors such as FLT3 inhibitors and IDH2 inhibitors), radiation treatment and/or surgery 7 days prior to starting conditioning regimen. Those who have not recovered sufficiently from adverse events due to agents administered more than 2 weeks earlier are also ineligible. Exceptions may be made on a case-by-case basis after discussion with the PI
  • Uncontrolled central nervous system (CNS) disease (for hematologic malignancies) Per PI discretion
  • Child-Pugh class B and C liver failure
  • Concomitant active malignancy that would be expected to require chemotherapy within 3 years of transplant (other than non-melanoma skin cancer) Exception would include any concurrently existing malignancy that could be treated with a transplant per PI discretion (Example: Patient has AML but a history of mastocytosis)
  • Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs; patients who previously have received a higher than allowed dose of radiation to a small lung, liver and brain volume, will be evaluated by the radiation oncologist to determine if the patient is eligible for study
  • Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
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  • Known human immunodeficiency virus (HIV) positive
  • Pregnant or nursing female participants
  • Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening
  • Patients with donor specific HLA antibodies with a titer greater than 3000 MFI (whether or not they have undergone a desensitization protocol)
  • Patients who have undergone a prior allogeneic hematopoietic or (other organ) transplant
  • Treating physician considers the potential HLA haploidentical donor to be ineligible to receive G-CSF, and/or concern on the part of the treating physician for risk of harm to the potential donor with administration of G-CSF, and/or refusal by the potential donor (or donor's guardian) to receive G-CSF
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug
  • Received an investigational agent within 14 days prior to enrollment. Exceptions may be made on a case-by-case basis after discussion with PI

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase II Trial of Haploidentical Allogeneic Stem Cell Transplantation Utilizing Mobilized Peripheral Blood Stem Cells

This phase II trial studies how well fludarabine phosphate, cyclophosphamide, total body irradiation, and donor stem cell transplant work in treating patients with blood cancer. Drugs used in chemotherapy, such as fludarabine phosphate and cyclophosphamide, 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 chemotherapy and total-body irradiation before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem 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. The donated stem cells may also replace the patient?s immune cells and help destroy any remaining cancer cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To evaluate the rate of relapse, defined as recurrence of underlying disease or progression of underlying disease, at 1 year in patients who receive haploidentical peripheral blood stem cells (PBSCs) after reduced intensity conditioning and post-transplant cyclophosphamide and tocilizumab (or tocilizumab alternative).

SECONDARY OBJECTIVES:

  1. To evaluate safety including development of acute graft versus host disease (GVHD) and death at 100 days post-transplant, as well as other treatment related toxicities including chronic GVHD, engraftment rate, non-relapse mortality, progression free survival (PFS) at one year, and overall survival (OS) at one year, as compared with historical controls.

TERTIARY OBJECTIVES:

  1. Correlative studies will include chimerism analysis by molecular analysis and evaluation of immune reconstitution by cytomegalovirus (CMV) dextramer analysis using flow cytometry.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo total body irradiation (TBI) on days -1 and peripheral blood stem cell transplantation (PBSCT) on day 0.

After completion of study treatment, patients are followed up at 30 and 100 days.

Medical subject headings
Leukemia, Myeloid, Accelerated Phase, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Anemia, Aplastic, Lymphoma, B-Cell, Granulomatous Disease, Chronic, Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Myelogenous, Chronic, BCR-ABL Positive

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

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Peripheral Blood Stem Cell TransplantationProcedure or surgery

    Also called PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support

    Undergo PBSCT

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT03333486
Study groupRoleWhat they receive
Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)ExperimentalPatients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 2 hours on days -6 and -5. Patients undergo TBI on days -1 and PBSCT on day 0.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Total-Body Irradiation

What is being measured

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

  1. Relapse Rate

    The number of participants that relapse within 1 year.

    Measured: At 1 year

Secondary outcomes (7)

  1. ANC Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment

    Absolute Neutrophil Count Engraftment rate was defined as the number of participants that received an engraftment within 1 year post-transplant and ANC > 0.5x10^9/L for three consecutive days, out of the total number of participants. The rate was computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

    Measured: At 1 year post-transplant

  2. Platelet Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment

    Platelet Engraftment rate was defined as the number of participants that received an engraftment within 1 year post-transplant and the platelets >= 20 x 10^9/L after 7 consecutive days with no platelet transfusions, out of the total number of participants. The rate was computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

    Measured: At 1 year post-transplant

  3. Proportion of Participants With Acute Graft Versus Host Disease (GVHD)

    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

    Measured: At 100 days post-transplant

  4. Proportion of Participants With Chronic Graft Versus Host Disease (GVHD)

    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

    Measured: At 1 year post-transplant

  5. Overall Survival

    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.

    Measured: up to 5 years and 8 months

  6. Progression Free Survival

    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson. Will be obtained using the product-limit based Kaplan-Meier method.

    Measured: up to 5 years and 8 months

  7. Transplant Related Mortality

    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.

    Measured: At 1 year 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 Nov 2017
  2. Study start7 Dec 2017
  3. Primary completion28 Aug 2023
  4. Study completion28 Aug 2023

Why it stopped: Futility analysis determined closure

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03333486
Sponsor's protocol ID
I 40916
Other IDs
NCI-2017-01949, I 40916
Status last verified
Jun 2025
First submitted
2 Nov 2017
Last updated
4 Jul 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, Fludarabine Phosphate and Laboratory Biomarker Analysis in people with Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Acute Leukemia in Remission, run by Roswell Park Cancer Institute 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 16 inclusion and 14 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: stopped early, as of the sponsor's last update on 4 Jul 2025. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Relapse Rate (time frame: At 1 year). 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 NCT03333486.

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 4 Jul 2025.

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