Clinical Trials /

Combination Chemotherapy, Total Body Irradiation, and Donor Blood Stem Cell Transplant in Treating Participants With Primary or Secondary Myelofibrosis

NCT03426969

Description:

This early phase I trial studies the side effects of combination chemotherapy, total body irradiation, and donor blood stem cell transplant in treating participants with primary or secondary myelofibrosis. Drugs used in chemotherapy, such as melphalan, fludarabine phosphate, cyclophosphamide, tacrolimus, mycophenolate mofetil, and filgrastim 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 combination chemotherapy and total body irradiation before a donor blood stem cell transplant helps to stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer 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.

Related Conditions:
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: HLA-Haploidentical SCT+ Post SCT Cy for Advanced Myelofibrosis
  • Official Title: A Pilot Study of Reduced Intensity HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Advanced Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: 2017-0375
  • NCT ID: NCT03426969

Conditions

  • Myelofibrosis

Interventions

DrugSynonymsArms
MelphalanAlkeran, EvomelaHaplo-HCT + Cyclophosphamide
FludarabineFludarabine Phosphate, FludaraHaplo-HCT + Cyclophosphamide
CyclophosphamideHaplo-HCT + Cyclophosphamide
TacrolimusPrografHaplo-HCT + Cyclophosphamide
Mycophenolate MofetilMMF, CellCeptHaplo-HCT + Cyclophosphamide
G-CSFFilgrastim, NeupogenHaplo-HCT + Cyclophosphamide

Purpose

The goal of this clinical research study is to learn about the safety of giving a stem cell transplant from a tissue-mismatched (haploidentical) donor, followed by cyclophosphamide, to patients with advanced myelofibrosis (MF). Melphalan, fludarabine, and total body irradiation (TBI) will also be given before the transplant as part of your standard care. In this study, researchers also want to learn if cyclophosphamide can help to prevent graft-versus-host disease (GVHD -- when transplanted immune tissue, such as the donor's tissue, attacks the tissues of the recipient's body). This is an investigational study. All of the drugs, including TBI, used in this study are FDA approved and commercially available for the treatment of MF. It is considered part of your standard care. However, it is investigational to use a haploidentical donor in patients with myelofibrosis. The study doctor can explain how the study drugs are designed to work. Up to 12 participants will be enrolled in this study. All will take part at MD Anderson.

Detailed Description

      Central Venous Catheter:

      The chemotherapy, some of the other drugs in this study, and the stem cell transplant will be
      given by vein through a central venous catheter (CVC). A CVC is a sterile flexible tube and
      needle that will be placed into a large vein while you are under local anesthesia. Some blood
      samples will also be drawn through your CVC. The CVC will remain in your body during
      treatment. Your doctor will explain this procedure to you in more detail, and you will be
      required to sign a separate consent form.

      Study Treatment Administration:

      The days before you receive your stem cells are called minus days. The day you receive the
      stem cells is called Day 0. The days after you receive the stem cells are called plus days.

      On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you.

      On Day -5, you will receive melphalan by vein over 30 minutes and fludarabine by vein over 1
      hour.

      On Days -4 through -2, you will receive fludarabine by vein over 1 hour.

      On Day -1, you will receive one dose of TBI. You will receive a separate consent form
      describing TBI and its administration in more detail, including its risks.

      On Day 0, you will receive the donor's stem cells by vein. This may last anywhere from 15
      minutes to several hours.

      On Days 3 and 4, you will receive cyclophosphamide by vein over 3 hours. You may also receive
      mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses on Days 3 and 4.
      Mesna is given to lower the risk of side effects to the bladder.

      Starting on Day 5, you will receive tacrolimus and mycophenolate mofetil (MMF) to help lower
      the risk of GVHD. Tacrolimus will be given by vein as a continuous (non-stop) infusion for
      about 2 weeks. After the 2 weeks of taking tacrolimus by vein, you will take tacrolimus by
      mouth as a pill for at least 3 months. MMF will be given by mouth, 3 times a day, usually
      until Day 35.

      Starting on Day 7, you will receive filgrastim (G-CSF) 1 time a day as an injection under the
      skin, until your blood cell counts reach a high enough level.

      Study Tests:

      As part of your standard care, you will stay in the hospital for about 3-4 weeks after the
      transplant. While you are in the hospital, blood (about 2 teaspoons) will be drawn every day
      to check for side effects, for routine tests, to check your blood counts, to check your
      kidney and liver function, and to check for infections.

      After you are sent home from the hospital, you must remain in the Houston area to be checked
      for infections and other transplant side effects until about 3 months after transplant.
      During this time, you will return to the clinic at least 1 time each week. At each visit,
      blood (about 2 teaspoons) will be drawn for routine tests.

      Follow-Up Visits:

      At Months 1, 3, 6, 9, and 12, when possible, blood (about 2 teaspoons) will be drawn to check
      your immune system function.

      At Months 1, 3, 6, 12, and 24, you will also have a bone marrow aspiration and/or blood
      (about 2 teaspoons) will be drawn to check the status of the disease. To collect a bone
      marrow aspirate, an area of the hip or other site is numbed with anesthetic, and a small
      amount of bone marrow is withdrawn through a large needle.

      If the study doctor thinks it is needed based on side effects you may be having, additional
      follow-up tests will be performed.

      Length of Study Participation:

      You will be on this study for up to about 2 years. You will be taken off study if the disease
      gets worse. The study drugs will be stopped if intolerable side effects occur.
    

Trial Arms

NameTypeDescriptionInterventions
Haplo-HCT + CyclophosphamideExperimentalParticipants receive stem cell transplant from a tissue-mismatched (haploidentical) donor, followed by cyclophosphamide. Melphalan, fludarabine, and total body irradiation (TBI) also given before the transplant as standard care.
  • Melphalan
  • Fludarabine
  • Cyclophosphamide
  • Tacrolimus
  • Mycophenolate Mofetil
  • G-CSF

Eligibility Criteria

        Inclusion Criteria:

          1. Diagnosis of primary or secondary Myelofibrosis with transplant indication by
             DIPSS-plus (> intermediate -1);

          2. Age 18-70; patients >/= age 50 must have an comorbidity score (HCT-CI) </= 4 (Sorror).
             The Principal Investigator is the final arbiter for comorbidity;

          3. Patients can be in chronic phase (CP) with BM blast count </= 10% or after progression
             to AML and achieved </= 5% BM blasts (morphologic CR prior to transplant);

          4. Lack of an HLA matched donor or need to proceed fast to transplantation when a patient
             does not have an immediately available matched unrelated donor (typed by
             high-resolution in the registry);

          5. Performance status >/=70% (Karnofsky); patients > 50 years should have adequate
             cognitive function; any concerns regarding cognitive function should be addressed by a
             Geriatrician/Neurologist;

          6. Adequate organ function: ALT/AST/bilirubin </= 5X UNL, creatinine clearance >
             50mls/min (calculated with Cockcroft-Gault formula); LVEF >/= 50%, DLCOc >/= 50%;

          7. Prior treatment with JAK2 inhibitor therapy is not excluded. Patients on a JAK2
             inhibitor may continue through conditioning until Day -3 then tapered at the
             discretion of the investigator.

        Exclusion Criteria:

          1. Evidence of portal hypertension with varices, ascites, or hepatic encephalopathy;

          2. >10% bone marrow blasts at transplant if no history of AML and >5% if had previous
             progression to AML;

          3. HIV positive; active hepatitis B or C;

          4. Patients with active infections. The PI is the final arbiter of the eligibility;

          5. Liver cirrhosis;

          6. Prior CNS involvement by tumor cells;

          7. Severe pulmonary hypertension (PHT) (On echo or right side cardiac catheterization);

          8. History of another primary malignancy that has not been in remission for at least 3
             years (the following are exempt from the 3-year limit: non-melanoma skin cancer, fully
             excised melanoma in situ [Stage 0], curatively treated localized prostate cancer, and
             cervical or breast carcinoma in situ on biopsy or a squamous intraepithelial lesion on
             PAP smear);

          9. Positive Beta HCG test in a woman with child bearing potential defined as not
             post-menopausal for 12 months or no previous surgical sterilization;

         10. Noncompliance - Inability or unwillingness to comply with medical recommendations
             regarding therapy or follow-up, including smoking tobacco. Smoking cessation is a
             standard teaching practice prior to admission for all patients undergoing stem cell
             transplant. Any patient who refuses to stop smoking prior to transplant will not be
             eligible for this study.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicities of HLA-Haploidentical SCT+ Post SCT Cy for Advanced Myelofibrosis scored using the NCI Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 4.03.
Time Frame:Toxicities recorded from the start of protocol treatment through day +100 post-HCT.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Time to neutrophil recovery defined as the first of 3 measurements on different days when the patient has an absolute neutrophil count of ≥500/ýL after conditioning.
Time Frame:Daily up to 4 weeks after transplant
Safety Issue:
Description:
Measure:Time to Platelet Recovery
Time Frame:Daily up to 4 weeks after transplant
Safety Issue:
Description:Time to platelet recovery defined as the first day of a minimum of 3 measurements on different days that the patient has achieved a platelet count ≥20,000/ýL AND did not receive a platelet transfusion in the previous 7 days.
Measure:Graft Failure-Free Survival (GFS)
Time Frame:After transplant up to 2 years
Safety Issue:
Description:GFS defined as time from start of protocol treatment/infusion of stem cell product to graft-failure, death (from any cause), or last contact, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:After transplant up to 2 years
Safety Issue:
Description:OS defined as time from start of protocol treatment/infusion of stem cell product to death (from any cause), or last contact, whichever occurs first.
Measure:Progression Free Survival (PFS)
Time Frame:After transplant up to 2 years
Safety Issue:
Description:PFS defined as time from start of protocol treatment/infusion of stem cell product to, relapse, progression, death (from any cause), or last contact, whichever occurs first.
Measure:Cumulative Incidence of Relapse/Progression (CIR)
Time Frame:After transplant up to 2 years
Safety Issue:
Description:The event is relapse/progression. CIR described post-start of protocol treatment and post-HCT. Death without relapse/progression is considered a competing risk.
Measure:Non-Relapse Mortality (NRM)
Time Frame:After transplant up to 2 years
Safety Issue:
Description:The event is death from causes other than relapse or progression. NRM described post-start of protocol treatment and post-HCT. Disease relapse/progression are considered competing risks.
Measure:Cumulative Incidence of Acute GvHD
Time Frame:From Day 0 up to Day +100 post-HCT.
Safety Issue:
Description:Acute GvHD assessed and graded according to the Keystone Consensus on GVHD scoring system (Przepiorka, Weisdorf et al. Acute GvHD described post-HCT. Time to the first day of acute GvHD onset (of any grade) used to estimate the cumulative incidence.
Measure:Cumulative Incidence of Chronic GvHD:
Time Frame:Day 100 up to 2 years post-HCT
Safety Issue:
Description:Chronic GvHD assessed and graded according to the NIH Consensus Criteria. Time to the first day of chronic GvHD onset (of any grade) used to estimate the cumulative incidence.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Trial Keywords

  • Myelofibrosis
  • MF
  • Haploidentical hematopoietic cell transplantation
  • Haplo-HCT
  • Melphalan
  • Alkeran
  • Evomela
  • Fludarabine
  • Fludarabine phosphate
  • Fludara
  • Tacrolimus
  • Prograf
  • Mycophenolate Mofetil
  • MMF
  • CellCept
  • G-CSF
  • Filgrastim
  • Neupogen
  • Total body irradiation
  • TBI
  • External beam radiation therapy

Last Updated

March 13, 2018