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

  • STATUS
    Recruiting
  • End date
    Sep 6, 2023
  • participants needed
    58
  • sponsor
    Roswell Park Cancer Institute
Updated on 24 January 2021
cancer
immunosuppressant
chronic myeloid leukemia
stem cell transplantation
myeloid leukemia
lymphoid leukemia
total body irradiation
fludarabine
hematologic malignancy
anemia
blood stem cell transplant
imatinib
cyclophosphamide
chronic lymphocytic leukemia
immunodeficiency
tyrosine
chromosomal abnormalities
lymphoma
myelofibrosis
myelodysplastic syndromes
multiple myeloma
anti-thymocyte globulin
hodgkin's disease
acute leukemia
myelodysplasia
immunosuppressive
white blood cell count
chronic myelomonocytic leukemia
calcineurin inhibitor
carbon monoxide
ejection fraction
waldenstrom's macroglobulinemia
secondary aml
cell transplantation
leukemia
x-rays
bone marrow procedure
lymphocytic leukemia
transplant conditioning
reduced intensity conditioning
antithymocyte globulin
thrombocytopenia
autologous transplant
autologous transplantation
secondary acute myeloid leukemia
cytotoxic chemotherapy
schwartz
white blood cells
progressive disease
chemotherapy regimen
chromosome abnormalities
autograft
wbc count
cancer chemotherapy
immunosuppressants
myelomonocytic leukemia
b-cell lymphoma
immunoglobulin
conditioning regimen
immune disorder
aplastic anemia
pancytopenia
diamond-blackfan anemia
kostmann syndrome
neutropenia
splenectomy
immune globulin
blood cell count
hemoglobinopathy
bone marrow failure
chromosomal abnormality
sickle cell anemia
kostmann's syndrome
wiskott-aldrich syndrome
lymphoproliferative disease
polycythemia vera
thalassemia
glanzmann's thrombasthenia
secondary myelodysplastic syndrome
shwachman-diamond syndrome
bone marrow failure syndromes
thrombasthenia
chronic granulomatous disease
chromosome abnormality
bone marrow failure disorders
lymphocyte immune globulin
eculizumab
severe combined immunodeficiency
cytotoxic therapy
polycythemia
flt3-itd
cytogenetic abnormalities
congenital neutropenia
b cell lymphoma

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.

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.

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.

Details
Condition Bone marrow disorder, Diamond-Blackfan anemia, childhood ALL, Wiskott-Aldrich Syndrome, Chronic myelomonocytic leukemia, Multiple Myeloma, Thalassemia, Juvenile Myelomonocytic Leukemia, Immunodeficiency, Preleukemia, Paroxysmal nocturnal hemoglobinuria, Thrombasthenia, Anemia, Aplastic Anemia, Waldenstrom's Macroglobulinemia, Acute myeloid leukemia, Thrombocytopathy, Myelosclerosis with myeloid metaplasia, Chronic granulomatous disease, Lymphoproliferative Disorder, Chronic Lymphocytic Leukemia, B-Cell Lymphoma, T-Cell Lymphoma, MYELOPROLIFERATIVE DISORDER, MYELODYSPLASTIC SYNDROME, SICKLE CELL ANEMIA, chronic phase chronic myelogenous leukemia, Accelerated Phase Chronic Myelogenous Leukemia, Chronic myeloid leukemia, Polycythemia Vera, Platelet Deficiencies, Lymphocytic Leukemia, Chronic, Lymphoma, B-Cell, Myelodysplastic Syndromes (MDS), Acute Myelogenous Leukemia (AML), Severe Aplastic Anemia, CD40 Ligand Deficiency, Refractory Non Hodgkin Lymphoma, Secondary Acute Myeloid Leukemia, Secondary Myelodysplastic Syndrome, Acute Leukemia in Remission, Acute Myeloid Leukemia With Gene Mutations, Myeloproliferative Neoplasms, Shwachman-Diamond Syndrome, Immune Deficiency, Anemia; Non-Small-Cell Lung Cancer, Primary Immunodeficiency Disorders, Lymphocytic Leukemia, Acute, Anemia; Non-Hodgkin’s Lymphoma, Hemoglobinuria, Paroxysmal, Acute Myeloid Leukemia With FLT3/ITD Mutation, Chronic Leukemia in Remission, Congenital Amegakaryocytic Thrombocytopenia, Congenital Neutropenia, Congenital Pure Red Cell Aplasia, Recurrent Non-Hodgkin Lymphoma, Shwachman-Diamond Syndrome, Acute Myeloid Leukemia With FLT3/ITD Mutation, Recurrent Non-Hodgkin Lymphoma, Shwachman-Diamond Syndrome, Shwachman Diamond Syndrome, Myelofibrosis, Platelet Disorders, Sickle Cell Disease, Lymphoproliferative disorders, Waldenstrom Macroglobulinemia, Acute Myeloid Leukemia With FLT3/ITD Mutation, Recurrent Non-Hodgkin Lymphoma, Acute Myeloid Leukemia With FLT3/ITD Mutation, Recurrent Non-Hodgkin Lymphoma, Acute Myeloid Leukemia With FLT3/ITD Mutation, Recurrent Non-Hodgkin Lymphoma, acute lymphoblastic leukemia, leukemia, acute lymphoblastic, myelodysplastic syndromes, myeloproliferative neoplasm, myeloproliferative disorders, leukemia chronic lymphocytic, chronic lymphocytic leukemia (cll), small lymphocytic lymphoma, immunodeficient, immunodeficiencies, decreased immune function, multiple myeloma (mm), myelodysplastic syndrome (mds), secondary aml, glanzmann's thrombasthenia, thromboasthenia, acute lymphoid leukaemia, acute lymphocytic leukemia, acute lymphoblastic leukemia (all), acute myelogenous leukemia, anll, acute myeloblastic leukemia, kostmann syndrome, kostmann's syndrome, kostmann, chronic myelomonocytic leukaemia, cmml, secondary mds, Acute Myeloid Leukemia With FLT3/ITD Mutation, Recurrent Non-Hodgkin Lymphoma
Treatment cyclophosphamide, fludarabine phosphate, laboratory biomarker analysis, peripheral blood stem cell transplantation, Total-Body Irradiation
Clinical Study IdentifierNCT03333486
SponsorRoswell Park Cancer Institute
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

Phone Email

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

cancer
immunosuppressant
chronic myeloid leukemia
stem cell transplantation
myeloid leukemia
lymphoid leukemia
total body irradiation
fludarabine
hematologic malignancy
anemia
blood stem cell transplant
imatinib
cyclophosphamide
chronic lymphocytic leukemia
immunodeficiency
tyrosine
chromosomal abnormalities
lymphoma
myelofibrosis
myelodysplastic syndromes
multiple myeloma
anti-thymocyte globulin
hodgkin's disease
acute leukemia
myelodysplasia
immunosuppressive
white blood cell count
chronic myelomonocytic leukemia
calcineurin inhibitor
carbon monoxide
ejection fraction
waldenstrom's macroglobulinemia
secondary aml
cell transplantation
leukemia
x-rays
bone marrow procedure
lymphocytic leukemia
transplant conditioning
reduced intensity conditioning
antithymocyte globulin
thrombocytopenia
autologous transplant
autologous transplantation
secondary acute myeloid leukemia
cytotoxic chemotherapy
schwartz
white blood cells
progressive disease
chemotherapy regimen
chromosome abnormalities
autograft
wbc count
cancer chemotherapy
immunosuppressants
myelomonocytic leukemia
b-cell lymphoma
immunoglobulin
conditioning regimen
immune disorder
aplastic anemia
pancytopenia
diamond-blackfan anemia
kostmann syndrome
neutropenia
splenectomy
immune globulin
blood cell count
hemoglobinopathy
bone marrow failure
chromosomal abnormality
sickle cell anemia
kostmann's syndrome
wiskott-aldrich syndrome
lymphoproliferative disease
polycythemia vera
thalassemia
glanzmann's thrombasthenia
secondary myelodysplastic syndrome
shwachman-diamond syndrome
bone marrow failure syndromes
thrombasthenia
chronic granulomatous disease
chromosome abnormality
bone marrow failure disorders
lymphocyte immune globulin
eculizumab
severe combined immunodeficiency
cytotoxic therapy
polycythemia
flt3-itd
cytogenetic abnormalities
congenital neutropenia
b cell lymphoma

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note