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

      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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Relapse rate

Secondary Outcome

 Engraftment rate

Condition

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive

Intervention

Cyclophosphamide

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.

Publications

* 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

Drug

Estimated Enrollment

31

Start Date

December 7, 2017

Completion Date

November 6, 2023

Primary Completion Date

November 6, 2022

Eligibility Criteria

        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
      

Gender

All

Ages

1 Year - 75 Years

Accepts Healthy Volunteers

No

Contacts

Christine Ho, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03333486

Organization ID

I 40916

Secondary IDs

NCI-2017-01949

Responsible Party

Sponsor

Study Sponsor

Roswell Park Cancer Institute


Study Sponsor

Christine Ho, MD, Principal Investigator, Roswell Park Cancer Institute


Verification Date

September 2022