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HLA-Haploidentical SCT+ Post SCT Cy for Advanced Myelofibrosis

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ClinicalTrials.gov Identifier: NCT03426969
Recruitment Status : Recruiting
First Posted : February 8, 2018
Last Update Posted : July 23, 2018
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

February 2, 2018
February 8, 2018
July 23, 2018
January 31, 2018
November 2019   (Final data collection date for primary outcome 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. ]
Same as current
Complete list of historical versions of study NCT03426969 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Time to Platelet Recovery [ Time Frame: Daily up to 4 weeks after transplant ]
    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.
  • Graft Failure-Free Survival (GFS) [ Time Frame: After transplant up to 2 years ]
    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.
  • Overall Survival (OS) [ Time Frame: After transplant up to 2 years ]
    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.
  • Progression Free Survival (PFS) [ Time Frame: After transplant up to 2 years ]
    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.
  • Cumulative Incidence of Relapse/Progression (CIR) [ Time Frame: After transplant up to 2 years ]
    The event is relapse/progression. CIR described post-start of protocol treatment and post-HCT. Death without relapse/progression is considered a competing risk.
  • Non-Relapse Mortality (NRM) [ Time Frame: After transplant up to 2 years ]
    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.
  • Cumulative Incidence of Acute GvHD [ Time Frame: From Day 0 up to Day +100 post-HCT. ]
    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.
  • Cumulative Incidence of Chronic GvHD: [ Time Frame: Day 100 up to 2 years post-HCT ]
    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.
Same as current
Not Provided
Not Provided
 
HLA-Haploidentical SCT+ Post SCT Cy for Advanced Myelofibrosis
A Pilot Study of Reduced Intensity HLA-Haploidentical Hematopoietic Cell Transplantation With Post-Transplant Cyclophosphamide in Patients With Advanced Myelofibrosis

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.

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.

Interventional
Early Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Myelofibrosis
  • Drug: Melphalan
    100 mg/m2 by vein on Day -5.
    Other Names:
    • Alkeran
    • Evomela
  • Drug: Fludarabine
    40 mg/m2 by vein on Days -4 to -2.
    Other Names:
    • Fludarabine Phosphate
    • Fludara
  • Radiation: Total Body Irradiation (TBI)
    TBI 200 cGy on Day -1.
    Other Name: External beam radiation therapy
  • Procedure: Stem Cell Infusion
    Bone marrow or PB stem cell infusion on Day 0.
  • Drug: Cyclophosphamide
    50 mg/kg/day by vein on Days +3 and +4.
  • Drug: Tacrolimus
    Tacrolimus starts at 0.015 mg/kg (then adjusted to a level 8-15ng/mL) as a continuous infusion by vein daily starting Day +5, then continued by mouth for 6 months post-transplant followed by a taper, unless GVHD present.
    Other Name: Prograf
  • Drug: Mycophenolate Mofetil
    Mycophenolate Mofetil 15 mg/kg (max 1000 mg per dose, based on actual body weight) by mouth three times a day given from Day +5 until Day+100 unless otherwise indicated.
    Other Names:
    • MMF
    • CellCept
  • Drug: G-CSF
    G-CSF 5 mcg/kg/day administered subcutaneously (SQ) daily starting Day +7 and continued until continued until ANC >1,500/mm3 for 3 consecutive days.
    Other Names:
    • Filgrastim
    • Neupogen
Experimental: Haplo-HCT + Cyclophosphamide
Participants 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.
Interventions:
  • Drug: Melphalan
  • Drug: Fludarabine
  • Radiation: Total Body Irradiation (TBI)
  • Procedure: Stem Cell Infusion
  • Drug: Cyclophosphamide
  • Drug: Tacrolimus
  • Drug: Mycophenolate Mofetil
  • Drug: G-CSF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
12
Same as current
November 2020
November 2019   (Final data collection date for primary outcome measure)

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.
Sexes Eligible for Study: All
18 Years to 70 Years   (Adult, Older Adult)
No
Contact: Stefan Ciurea, MD 713-792-8750 sciurea@mdanderson.org
United States
 
 
NCT03426969
2017-0375
NCI-2018-00910 ( Registry Identifier: NCI CTRP )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Not Provided
M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
Not Provided
Principal Investigator: Stefan Ciurea, MD M.D. Anderson Cancer Center
M.D. Anderson Cancer Center
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP