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TerminatedNCT03333486Updated Jul 4, 2025Results posted

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

A Phase 2 interventional study of Cyclophosphamide and Fludarabine Phosphate in Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Acute Leukemia in Remission and Acute Lymphoblastic Leukemia, sponsored by Roswell Park Cancer Institute. Terminated at 1 site in United States. Open to participants aged 1 Year to 75 Years. Per ClinicalTrials.gov, last updated 2025-07-04.

Sponsored by Roswell Park Cancer Institute · Phase 2, Interventional, and Treatment

Why this study was terminated
Futility analysis determined closure
Phase
Phase 2
Study type
Interventional
Enrollment
31
Allocation
Not applicable
Ages
1 Year to 75 Years
Sex
All
01

Study 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, 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:

I. 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:

I. 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:

I. 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.

02

Conditions studied

  • Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Acute Leukemia in Remission
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia With FLT3/ITD Mutation
  • Acute Myeloid Leukemia With Gene Mutations
  • Aplastic Anemia
  • B-Cell Non-Hodgkin Lymphoma
  • CD40 Ligand Deficiency
  • Chronic Granulomatous Disease
  • Chronic Leukemia in Remission
  • Chronic Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Myelomonocytic Leukemia
  • Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Congenital Amegakaryocytic Thrombocytopenia
  • Congenital Neutropenia
  • Congenital Pure Red Cell Aplasia
  • Glanzmann Thrombasthenia
  • Immunodeficiency Syndrome
  • Myelodysplastic Syndrome
  • Myelofibrosis
  • Myeloproliferative Neoplasm
  • Paroxysmal Nocturnal Hemoglobinuria
  • Plasma Cell Myeloma
  • Polycythemia Vera
  • Recurrent Non-Hodgkin Lymphoma
  • Refractory Non-Hodgkin Lymphoma
  • Secondary Acute Myeloid Leukemia
  • Secondary Myelodysplastic Syndrome
  • Severe Aplastic Anemia
  • Shwachman-Diamond Syndrome
  • Sickle Cell Disease
  • T-Cell Non-Hodgkin Lymphoma
  • Thalassemia
  • Waldenstrom Macroglobulinemia
  • Wiskott-Aldrich Syndrome
03

Who can participate

Ages eligible
1 Year to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.
  • 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

Exclusion criteria

  • 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
  • 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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
31 participants (actual)

Study arms

  • Experimental
    Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)

    Patients 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.

    Drug: Cyclophosphamide · Drug: Fludarabine Phosphate · Other: Laboratory Biomarker Analysis · Procedure: Peripheral Blood Stem Cell Transplantation · Radiation: Total-Body Irradiation

Interventions

  • DrugCyclophosphamide

    Given IV

    Also known as: (-)-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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

  • DrugFludarabine Phosphate

    Given IV

    Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

  • OtherLaboratory Biomarker Analysis

    Correlative studies

  • ProcedurePeripheral Blood Stem Cell Transplantation

    Undergo PBSCT

    Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support, Peripheral Stem Cell Transplant, peripheral stem cell transplantation

  • RadiationTotal-Body Irradiation

    Undergo TBI

    Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation

05

What researchers measure

Primary outcomes

  1. Relapse Rate

    The number of participants that relapse within 1 year.

    Time frame: At 1 year

Secondary outcomes

  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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: At 1 year post-transplant

Other outcomes

  1. Immune Reconstitution

    Will be assessed by bone marrow transplantation SOC immunophenotyping panel and by analysis of cytomegalovirus-specific immunity.

    Time frame: Up to 1 year

  2. Lymphoid Chimerism Expressed as a Percentage of Donor Cells

    Mean lymphoid chimerism expressed as a percentage of donor cells

    Time frame: At 30 days

  3. Myeloid Chimerism Expressed as a Percentage of Donor Cells

    Mean myeloid chimerism expressed as a percentage of donor cells

    Time frame: At 100 days

06

Results

Posted Apr 2, 2024

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Started31
Completed29
Not completed2
Withdrew: Withdrawal by subject1
Withdrew: Lost to follow-up1

Outcome measures

PrimaryRelapse Rate

The number of participants that relapse within 1 year.

Time frame:
At 1 year
Reported as:
Count of participants · Participants
Relapse Rate
ParticipantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Relapse Rate14
SecondaryANC 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.

Time frame:
At 1 year post-transplant
Reported as:
Number · percentage of participants
ANC Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment
percentage of participantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
ANC Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment84 (66.0 to 95.0)
SecondaryPlatelet 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.

Time frame:
At 1 year post-transplant
Reported as:
Number · percentage of participants
Platelet Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment
percentage of participantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Platelet Engraftment Rate, the Percentage of Participants That Had a Successful Engraftment77 (59 to 90)
SecondaryProportion 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.

Time frame:
At 100 days post-transplant
Reported as:
Number · proportion of participants
Proportion of Participants With Acute Graft Versus Host Disease (GVHD)
proportion of participantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Proportion of Participants With Acute Graft Versus Host Disease (GVHD)0.3226 (0.1668 to 0.5137)
SecondaryProportion 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.

Time frame:
At 1 year post-transplant
Reported as:
Number · proportion of participants
Proportion of Participants With Chronic Graft Versus Host Disease (GVHD)
proportion of participantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Proportion of Participants With Chronic Graft Versus Host Disease (GVHD)0.1935 (0.0745 to 0.3747)
SecondaryOverall 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.

Time frame:
up to 5 years and 8 months
Reported as:
Median · months
Overall Survival
monthsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Overall Survival15.7 (7.1 to NA)
SecondaryProgression 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.

Time frame:
up to 5 years and 8 months
Reported as:
Median · months
Progression Free Survival
monthsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Progression Free Survival15.7 (5.5 to 49.5)
SecondaryTransplant Related Mortality

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

Time frame:
At 1 year post-transplant
Reported as:
Number · proportion of participants
Transplant Related Mortality
proportion of participantsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Transplant Related Mortality0.0323 (0.0008 to 0.1670)
Other pre-specifiedImmune Reconstitution

Will be assessed by bone marrow transplantation SOC immunophenotyping panel and by analysis of cytomegalovirus-specific immunity.

Time frame:
Up to 1 year

Results for this outcome have not been posted.

Other pre-specifiedLymphoid Chimerism Expressed as a Percentage of Donor Cells

Mean lymphoid chimerism expressed as a percentage of donor cells

Time frame:
At 30 days
Reported as:
Mean · percentage of donor cells
Lymphoid Chimerism Expressed as a Percentage of Donor Cells
percentage of donor cellsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Lymphoid Chimerism Expressed as a Percentage of Donor Cells99.85 ± 0.46
Other pre-specifiedMyeloid Chimerism Expressed as a Percentage of Donor Cells

Mean myeloid chimerism expressed as a percentage of donor cells

Time frame:
At 100 days
Reported as:
Mean · percentage of donor cells
Myeloid Chimerism Expressed as a Percentage of Donor Cells
percentage of donor cellsTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Myeloid Chimerism Expressed as a Percentage of Donor Cells99.93 ± 0.22

Adverse events

Collected over 5 years and 8.5 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)17/31 (54.8%)8/31 (25.8%)27/31 (87.1%)
Most frequent serious events
Most frequent serious events
EventTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Infections and infestations - Other, specifyInfections and infestations2/31
SepsisInfections and infestations2/31
Febrile neutropeniaBlood and lymphatic system disorders1/31
Hepatic failureHepatobiliary disorders1/31
Immune system disorders - Other, specifyImmune system disorders1/31
Lung infectionInfections and infestations1/31
Investigations - Other, specifyInvestigations1/31
Platelet count decreasedInvestigations1/31
Nervous system disorders - Other, specifyNervous system disorders1/31
PneumonitisRespiratory, thoracic and mediastinal disorders1/31
Most frequent other events
Showing 10 of 85
Most frequent other events
EventTreatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
NauseaGastrointestinal disorders18/31
DiarrheaGastrointestinal disorders17/31
Febrile neutropeniaBlood and lymphatic system disorders14/31
FatigueGeneral disorders11/31
VomitingGastrointestinal disorders10/31
Edema limbsGeneral disorders10/31
AnorexiaMetabolism and nutrition disorders8/31
Cytokine release syndromeImmune system disorders7/31
Infections and infestations - Other, specifyInfections and infestations7/31
Lung infectionInfections and infestations6/31

Baseline characteristics

All treated and eligible patients

Age, Categorical
Age, Categorical(Participants)Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
<=18 years0
Between 18 and 65 years14
>=65 years17
Age, Continuous
Age, Continuous(years)Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Mean63 ± 9
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
Female11
Male20
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American4
White25
More than one race0
Unknown or Not Reported2
Region of Enrollment
Region of Enrollment(participants)Treatment (Fludarabine, Cyclophosphamide, TBI, PBSCT)
United States31
07

Study locations

1 site
  • Roswell Park Cancer Institute
    Buffalo, New York 14263, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 5, 2023

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03333486
Lead sponsor
Roswell Park Cancer Institute
Responsible party
Sponsor
First posted
Nov 7, 2017
Start date
Dec 7, 2017
Primary completion
Aug 28, 2023
Completion
Aug 28, 2023
Results posted
Apr 2, 2024
Last update
Jul 4, 2025

Study contacts

Philip McCarthy, MD
principal investigator · Roswell Park Cancer Institute

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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