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

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Brief Title

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

Official Title

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


      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 Phase

Phase 2

Study Type


Primary Outcome

Relapse rate

Secondary Outcome

 Engraftment rate


Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive



Study Arms / Comparison Groups

 Treatment (fludarabine, cyclophosphamide, TBI, PBSCT)
Description:  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.


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 7, 2017

Completion Date

September 6, 2023

Primary Completion Date

September 6, 2022

Eligibility Criteria

        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

                    -  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

                    -  Acute lymphoblastic leukemia (ALL) B cell or T cell

               -  Chronic myelocytic leukemia (CML):

                    -  Chronic phase (intolerant or unresponsive to imatinib and/or tyrosine kinase

                    -  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

                    -  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

                    -  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

          -  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

          -  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)

          -  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




1 Year - 75 Years

Accepts Healthy Volunteers



Sophia Balderman, 877-275-7724, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID

I 40916

Secondary IDs


Responsible Party


Study Sponsor

Roswell Park Cancer Institute


 National Cancer Institute (NCI)

Study Sponsor

Sophia Balderman, Principal Investigator, Roswell Park Cancer Institute

Verification Date

February 2021