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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03333486
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : December 20, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Roswell Park Cancer Institute

Tracking Information
First Submitted Date  ICMJE November 2, 2017
First Posted Date  ICMJE November 7, 2017
Last Update Posted Date December 20, 2018
Actual Study Start Date  ICMJE December 7, 2017
Estimated Primary Completion Date September 6, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
Relapse rate [ Time Frame: At 1 year ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03333486 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Engraftment rate [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
  • Incidence of acute graft versus host disease (GVHD) [ Time Frame: At 100 days post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
  • Incidence of chronic GVHD [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
  • Overall survival [ Time Frame: At 1 year post-transplant ]
    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.
  • Progression free survival [ Time Frame: At 1 year from time of transplant ]
    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.
  • Transplant related mortality [ Time Frame: At 1 year post-transplant ]
    Will be computed with corresponding exact 95% confidence intervals based on the methodology of Clopper and Pearson.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: November 2, 2017)
  • Immune reconstitution [ Time Frame: Up to 1 year ]
    Will be assessed by bone marrow transplantation SOC immunophenotyping panel and by analysis of cytomegalovirus-specific immunity.
  • Myeloid and lymphoid chimerism expressed as a percentage of donor cells [ Time Frame: At 30 days ]
  • Myeloid and lymphoid chimerism expressed as a percentage of donor cells [ Time Frame: At 100 days ]
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Fludarabine Phosphate, Cyclophosphamide, Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Blood Cancer
Official Title  ICMJE A Phase II Trial of Haploidentical Allogeneic Stem Cell Transplantation Utilizing Mobilized Peripheral Blood Stem Cells
Brief 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.
Detailed Description


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.


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.


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


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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-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
  • Drug: Fludarabine Phosphate
    Given IV
    Other Names:
    • 2-F-ara-AMP
    • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    • Beneflur
    • Fludara
    • SH T 586
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Procedure: Peripheral Blood Stem Cell Transplantation
    Undergo PBSCT
    Other Names:
    • PBPC transplantation
    • PBSCT
    • Peripheral Blood Progenitor Cell Transplantation
    • peripheral stem cell support
    • Peripheral Stem Cell Transplant
    • peripheral stem cell transplantation
  • Radiation: Total-Body Irradiation
    Undergo TBI
    Other Names:
    • Whole-Body Irradiation
Study Arms  ICMJE 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 2, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 6, 2022
Estimated Primary Completion Date September 6, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The patient must have a diagnosis of one of the following (one must be yes):

    • Bone marrow failure disorders:

      • Acquired bone marrow failure disorders include aplastic anemia, paroxysmal nocturnal hemoglobinuria (PNH):

        • SAA must have failed at least one cycle of standard immunosuppressive therapy with calcineurin inhibitor plus anti-thymocyte globulin (ATG) if a fully-matched donor is not available
        • PNH must have failed treatment or not tolerated treatment with eculizumab or progressed during or after treatment with eculizumab)
      • Hereditary bone marrow failure disorders include Diamond-Blackfan anemia, Shwachman-Diamond syndrome, Kostmann syndrome, and congenital amegakaryocytic thrombocytopenia
    • Other non-malignant hematologic or immunologic disorders that require transplantation:

      • Quantitative or qualitative congenital platelet disorders (including but not limited to congenital amegakaryocytopenia, absent-radii syndrome, Glanzmann's thrombasthenia)
      • Quantitative or qualitative congenital neutrophil disorders (including but not limited to chronic granulomatous disease, congenital neutropenia)
      • Congenital primary immunodeficiencies (including but not limited to severe combined immunodeficiency syndrome, Wiskott-Aldrich syndrome, CD40 ligand deficiency, T-cell deficiencies)
      • Hemoglobinopathies (including sickle cell disease and thalassemia
    • Acute leukemias:

      • Acute myeloid leukemia (AML) - antecedent myelodysplastic syndrome, secondary AML, high risk cytogenetic abnormalities or normal cytogenetics with high-risk molecular mutations (including but not limiting to Flt3-ITD mutation)
      • Acute lymphoblastic leukemia (ALL) B cell or T cell
    • Chronic myelocytic leukemia (CML):

      • Chronic phase (intolerant or unresponsive to imatinib and/or tyrosine kinase inhibitors)
      • Second chronic phase or accelerated phase who are ineligible for conventional myeloablative transplantation
    • Myeloproliferative and myelodysplasia syndromes:

      • Myelofibrosis (with/without splenectomy) with intermediate to high risk features
      • Advanced polycythemia vera not responding to therapy
      • Myelodysplastic syndrome (MDS) with an International Prognostic Scoring System (IPSS) score of intermediate or higher
      • Secondary MDS with any IPSS score
      • Chronic myelomonocytic leukemia (CMML)
    • Lymphoproliferative disease:

      • Chronic lymphocytic leukemia (CLL), low-grade non-Hodgkin lymphoma (NHL) (recurrent or persistent) cytotoxic therapy refractory or with less than 6 months duration of complete response (CR) between courses of conventional therapy
      • Multiple myeloma (MM) progressive disease after auto bone marrow transplantation (BMT), tandem allo after prior auto
      • Waldenstrom?s macroglobulinemia (failed one standard regimen)
      • T or B cell lymphoma with poor risk features
      • Hodgkin disease:

        • Received and failed frontline therapy
        • Failed or not eligible for autologous transplantation
  • Suitable related haploidentical donor identified:

    • Must be matched at least at 5 of 10 HLA antigens (A, B, C,DRB1, DQ)
    • Must not be matched at more than 7 of 10 HLA antigens
    • 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 donor to whom the patient has HLA antibodies can be utilized as long as the antibody titer is less than 2000 median fluorescence intensity (MFI); if the titer is > or = to 2000 MFI, the recipient must undergo successful antibody desensitization prior to enrollment on this study; any patients who have demonstrated donor specific antibodies will not be evaluated for the end points measured in this study but will be followed for treatment related toxicities
    • 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 or legal representative 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
  • Patient in CR or has a bone marrow failure disorder or non-malignant hematologic or immune disorder : does NOT have a sibling donor or 12/12 HLA matched unrelated donor available OR treating clinician considers haploidentical transplant referable (despite sibling donor availability or 12/12 HLA matched donor availability) due to patient's clinical status.
  • Exclusion Criteria:
  • Participants who have had chemotherapy, radiation treatment and/or surgery 2 weeks prior to entering the study or, as per discretion of the treating physician, those who have not recovered sufficiently from adverse events due to agents administered more than 2 weeks earlier
  • Uncontrolled central nervous system (CNS) disease (for hematologic malignancies)
  • 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)
  • 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 2000 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 30 days prior to enrollment
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 75 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ASK RPCI 877-275-7724
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03333486
Other Study ID Numbers  ICMJE I 40916
NCI-2017-01949 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
I 40916 ( Other Identifier: Roswell Park Cancer Institute )
P30CA016056 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roswell Park Cancer Institute
Study Sponsor  ICMJE Roswell Park Cancer Institute
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Sophia Balderman Roswell Park Cancer Institute
PRS Account Roswell Park Cancer Institute
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP