Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

Brief Title

Fludarabine Phosphate, Low-Dose Total Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With Hematologic Malignancies or Kidney Cancer

Official Title

Low-Dose TBI and Fludarabine Followed by Unrelated Donor Stem Cell Transplantation for Patients With Hematologic Malignancies and Renal Cell Carcinoma - A Multi-center Trial

Brief Summary

      This clinical trial studies fludarabine phosphate, low-dose total body irradiation, and donor
      stem cell transplant in treating patients with hematologic malignancies or kidney cancer.
      Giving chemotherapy drugs, such as fludarabine phosphate, and total-body irradiation before a
      donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may
      also stop the patient's immune system from rejecting the donor's stem cells. The donated stem
      cells may replace the patient's immune cells and help destroy any remaining cancer cells
      (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
      infusion) after the transplant may help increase this effect. Sometimes the transplanted
      cells from a donor can also make an immune response against the body's normal cells. Giving
      cyclosporine before the transplant and cyclosporine and mycophenolate mofetil after the
      transplant may stop this from happening.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine whether stable allogeneic engraftment from unrelated hematopoietic stem cell
      donors can be safely established using a non-myeloablative conditioning regimen in patients
      with hematologic malignancies and renal cell carcinoma.

      SECONDARY OBJECTIVES:

      I. To evaluate whether donor lymphocyte infusion (DLI) can be safely used in patients with
      mixed or full donor chimerism to eliminate persistent or progressive disease.

      OUTLINE:

      CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to
      -2. Patients also undergo low-dose total-body irradiation (TBI) on day 0.

      TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell (PBSC) or bone marrow
      transplantation on day 0.

      IMMUNOSUPPRESSION: Patients receive cyclosporine orally (PO) twice daily (BID) on days -3 to
      100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96.
      Patients with mixed chimerism, persistent or progressive disease, and no evidence of
      graft-versus-host disease and who have been off immunosuppression for at least 2 weeks
      undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

      After completion of study treatment, patients are follow-up periodically for 5 years.
    

Study Type

Interventional

Primary Outcome

Establishment of an allograft as defined by stable mixed chimerism or full donor chimerism

Secondary Outcome

 Disease-free survival

Condition

Accelerated Phase Chronic Myelogenous Leukemia

Intervention

fludarabine phosphate

Study Arms / Comparison Groups

 Treatment (chemotherapy, TBI, HSCT)

Description:  CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2. Patients also undergo low-dose TBI on day 0.
TRANSPLANTATION: Patients undergo allogeneic PBSC or bone marrow transplantation on day 0.
IMMUNOSUPPRESSION: Patients receive cyclosporine PO BID on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO BID on days 0-40 with taper to day 96. Patients with mixed chimerism, persistent or progressive disease, and no evidence of graft-versus-host disease and who have been off immunosuppression for at least 2 weeks undergo DLI over 30 minutes. DLI may be repeated every 65 days for up to 3 doses.

Publications

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

Recruitment Status

Drug

Estimated Enrollment

55

Start Date

November 1999

Primary Completion Date

July 2002

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 50 years with hematologic malignancies treatable by allogeneic hematopoietic
             stem cell transplant (HSCT) and all patients with B cell malignancies except those who
             may be cured by autologous stem cell transplantation (SCT)

          -  Age =< 50 years of age with hematologic diseases treatable by allogeneic HSCT who
             through pre-existing medical conditions or prior therapy are considered to be of high
             risk for regimen related toxicity associated with a conventional transplant or those
             patients who refuse a conventional SCT; transplants must be approved for these
             inclusion criteria by both the participating institution's patient review committee
             such as the Patient Care Conference (PCC at the Fred Hutchinson Cancer Research Center
             [FHCRC]) and by the principal investigator

          -  Patients with metastatic renal cell carcinoma with the histologic subtypes of clear
             cell, papillary and medullary may be accepted regardless of age

          -  The following diseases will be permitted although other diagnoses can be considered if
             approved by PCC or the participating institution's patient review committees and the
             principal investigator

               -  Non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), Hodgkin lymphoma
                  (HL) - must have received and failed frontline therapy

               -  Multiple myeloma - must have received prior chemotherapy; consolidation of
                  chemotherapy by autografting prior to nonmyeloablative HSCT is permitted

               -  Acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) - must be in
                  complete remission and have received cytotoxic chemotherapy at some stage before
                  transplant; patients with molecular or early relapse will be accepted providing a
                  donor is available; patients with persistent or refractory disease will be
                  considered on a case by case basis and transplants must be approved by the
                  institution's patient review committees

               -  Chronic myelogenous leukemia (CML) - patients will be accepted in chronic phase
                  or accelerated phase; patients who have received prior autografts after high dose
                  therapy or have undergone intensive chemotherapy for either peripheral blood stem
                  cell (PBSC) mobilization or treatment of advanced CML may be enrolled provided
                  they are in complete remission (CR), chronic phase (CP) or accelerated phase (AP)

               -  Myelodysplastic syndromes (MDS) - all patients with MDS will be eligible for this
                  protocol; however, those patients with MDS and frank AML (> 30% blasts in bone
                  marrow aspirate by morphology or flow cytometry) will require induction
                  chemotherapy to obtain a complete remission (marrow blasts < 5%) and remain in
                  complete remission at time of transplant

               -  Renal cell carcinoma- must have evidence of disease not amenable to surgical cure
                  or metastatic disease by radiological and histological criteria

          -  DONOR: Human leukocyte antigen (HLA) matched unrelated donor; donors should be matched
             for HLA -A, -B, -C, -developmentally regulated ribonucleic acid (RNA) binding protein
             1(DRB)1 and -class II, DQ beta 1 (DQB) 1; HLA -A and -B loci should be matched at
             least to the level of resolution; HLA -C, -DRB1, and -DQB1 should be typed at the
             highest level of resolution available at the time of donor selection; donor must
             consent to either a bone marrow harvest or PBSC mobilization with filgrastim (G-CSF)
             arranged through the National Marrow Donor Program (NMDP) or other donor centers

        Exclusion Criteria:

          -  Patients with rapidly progressive intermediate or high grade NHL

          -  Renal cell carcinoma patients with expected survival of less than 6 months

               -  Bulky disease resulting in severely limited performance status (< 70%)

               -  Any vertebral instability

          -  Any active central nervous system (CNS) involvement with disease

          -  Fertile men or women unwilling to use contraceptive techniques during and for 12
             months following treatment

          -  Females who are pregnant

          -  Patients with non-hematological tumors

          -  Cardiac ejection fraction < 30%

          -  Diffusion capacity of the lung for carbon monoxide (DLCO) < 30% and/or receiving
             supplementary continuous oxygen

          -  Significant elevation of bilirubin and transaminases should be discussed at
             participating institutions' patient review committees in a case by case basis;
             evidence of synthetic dysfunction or severe cirrhosis will result in patient exclusion

          -  Karnofsky score < 50 (except renal cell carcinoma [RCC])

          -  Patients with poorly controlled hypertension on multiple antihypertensives

          -  Human immunodeficiency virus (HIV) positive patients
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

No

Contacts

Brenda Sandmaier, , 

Location Countries

Germany

Location Countries

Germany

NCT ID

NCT00005799

Organization ID

1463.00

Secondary IDs

NCI-2012-00667

Responsible Party

Sponsor

Study Sponsor

Fred Hutchinson Cancer Research Center

Collaborators

 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Brenda Sandmaier, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Verification Date

September 2019