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T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia

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ClinicalTrials.gov Identifier: NCT03531736
Recruitment Status : Recruiting
First Posted : May 22, 2018
Last Update Posted : June 2, 2021
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE May 9, 2018
First Posted Date  ICMJE May 22, 2018
Last Update Posted Date June 2, 2021
Actual Study Start Date  ICMJE May 9, 2018
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 1, 2019)
Rate of donor Neutrophil Engraftment [ Time Frame: 30 days post-transplant ]
Neutrophil engraftment (recovery of ANC) defined by an ANC ≥ 500/mm^3 for 3 consecutive days
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2018)
Rate of donor Neutrophil Engraftment [ Time Frame: 30 days post-transplant ]
Neutrophil engraftment (recovery of ANC) defined by an ANC >500/mm^3 for 3 consecutive days
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE T Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia
Official Title  ICMJE Allogeneic Hematopoietic Stem Cell Transplantation of α/β T-Lymphocyte Depleted Graft Conditioned With a Reduced Intensity Regimen in Patients With Hematologic Malignancies and Aplastic Anemia
Brief Summary

The main purpose of this study is to learn if a new combination of chemotherapy, in combination with low-dose radiation, will be safe for the patient, and at the same time provide the best opportunity to cure the bone marrow cancer. The combination of chemotherapy and radiation described in the study is considered 'low intensity.' Although the chemotherapy agents used in this study and for transplant are FDA approved, the chemotherapy treatment and conditioning regimens or combinations listed in this consent are not yet FDA approved.

The CliniMACS device is FDA approved for one type of T cell depletion (positive selection of the stem cells) but not approved yet for other type of T cell depletion, which is being studied on this protocol. This pilot study, along with other studies will serve as the basis for FDA approval, if outcomes are favorable.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a pilot study to assess engraftment of a T cell depleted (TCD) graft following a reduced intensity conditioning regimen (RIC). The conditioning regimen will include total body irradiation (TBI), Fludarabine, anti-thymocyte globulin (ATG) and post transplant cyclophosphamide (PT-Cy). The graft will be TCD and will be composed of a TCR-α/β+ lymphocyte depletion stem cells and CD34+ selected stem cells.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myeloid Diseases
Intervention  ICMJE
  • Drug: Antithymocyte globulin (Rabbit)
    ATG (2 mg/kg/d IV on days-8 through -7)
    Other Name: ATG
  • Drug: fludarabine
    fludarabine (30 mg/m2/d on days -5 through -2)
  • Radiation: total body irradiation
    TBI 200 cGy (days -2 and -1) given post stem cell infusion
    Other Name: TBI
  • Drug: cyclophosphamide
    cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4)
  • Drug: Rituxan
    Rituxan (200 mg/m2) will be given to reduce the risk of EBV viremia
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
    Allogeneic Hematopoietic Stem Cell Transplantation
Study Arms  ICMJE Experimental: Patients with Myeloid Malignancies & Aplastic Anemia
Transplant conditioning will consist of: ATG (2 mg/kg/day IV on days-8 through-6), fludarabine (30 mg/m^2/d on days -5 through -2), TBI 400 cGy in 2 divided doses (days -2 and -1) and high dose cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4). One dose of Rituxan (200 mg/m^2) will be given to reduce the risk of EBV viremia. The donor stem cell product will be derived from the peripheral blood with a target cell infusion of ≥8X10^6 CD34 cells per recipient kg. Patients will receive post-transplant G-CSF starting on day +7. Patients will undergo donor/recipient bone marrow and peripheral chimerism studies at 30 and 100, and 6, 12, 18 and 24 months post allo HCT and thereafter, at the discretion of the treating clinician. Immune function and disease restaging will be performed at day 100 and 6, 12, 18, and 24 months and as otherwise clinically indicated by the treating physician.
Interventions:
  • Drug: Antithymocyte globulin (Rabbit)
  • Drug: fludarabine
  • Radiation: total body irradiation
  • Drug: cyclophosphamide
  • Drug: Rituxan
  • Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 9, 2018)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with one of the high risk myeloid diseases as outlined below. Patients must have ≤ 5% blasts on the last BM evaluation prior to starting the conditioning regimen. Diseases included on this protocol include:

    1. Acute Myeloid Leukemia (AML) in CR1 with intermediate or high risk features as defined below:

      °Cytogenetic abnormalities which are not considered "good risk" cytogenetic features (i.e t(8:21), t(15:17), inv 16 without c-kit mutations.

      And/or

      • Therapy related AML with history of antineoplastic therapy (radiation and/or chemotherapy) And/or
      • Normal karyotype with mutations of FLT3, RUNX1, TP53 mutation, ASXL1 or any others that are considered to be high risk
    2. AML in ≥ 2nd remission
    3. Myelodysplastic syndrome, myeloproliferative neoplasms, or MDS/MPN overlap syndrome with:

      °International prognostic scoring system risk score INT-2 or high risk at the time of transplant evaluation.

      And/or

      • Any risk category if life-threatening cytopenia exists And/or
      • Karyotype or genomic changes that indicate high risk for progression to acute myelogenous leukemia, including abnormalities of chromosome 7 or 3, mutations of TP53, or complex or monosomal karyotype.
    4. Chronic myelomonocytic leukemia (CMML)
    5. Chronic myeloid leukemia (CML) with the following features:

      °Patients who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.

      And/or

      °CML with BCR-ABL mutation consistent with poor response to tyrosine kinase inhibition (e.g T351l mutation)

    6. Patients with severe aplastic anemia
  • Chronic lymphocytic leukemia (CLL) with high risk disease as defined by the EBMT consensus criteria.
  • Non-Hodgkin lymphoma meeting both of the following criteria:

    • Responding to therapy prior to enrollment.
    • Relapse after prior autologous bone marrow transplant or are ineligible for autologous bone marrow transplant.
  • Multiple Myeloma with disease in the following categories:

    • Patients with relapsed multiple myeloma following autologous stem cell transplantation who have achieved at least partial response following additional chemotherapy
    • Patients with high risk cytogenetics at diagnosis must have achieved at least a partial response following autologous stem cell transplantation. Patients must have complex karyotype, del17p, t4;14, and/or t14;16 by FISH and/or del13 by karyotyping.
  • Each patient must be willing to participate as a research participant and must sign an informed consent form.
  • Organ Function and Performance Status Criteria:

    1. Patients be ≥ 18 years old.
    2. Patients must have a Karnofsky (adult) or Performance Status ≥ 70%.
    3. Patients must have adequate organ function measured by:

      • Cardiac: asymptomatic or if symptomatic, then LVEF at rest must be ≥ 40% and must improve with exercise.
      • Hepatic: < 5x ULN ALT and < 2x ULN total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
      • Renal: CrCl >30ml/min (measured or calculated/estimated).
      • Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)

Exclusion Criteria:

  • Prior allogenic hematopoietic stem cell transplantation
  • Prior radiation therapy with 400cGY or more of TBI
  • BM with increased fibrosis (Reticulin stain > 1/3)
  • Active and uncontrolled infection at time of transplantation
  • HIV infection
  • Seropositivity for HTLV-1
  • Inadequate performance status/ organ function
  • Pregnancy or breast feeding
  • Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up, and research tests.

Donor Inclusion and Exclusion Criteria:

  • Must be a 10/10 HLA genotypically match related or unrelated donor at all A, B, C, DRB1, and DQB1 loci, as tested by DNA analysis
  • Able to provide informed consent for the donation process per institutional standards
  • Meet standard criteria for donor collection as defined by the National Marrow Donor Program Guidelines
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Roni Tamari, MD 212-639-5987 tamarir@mskcc.org
Contact: Miguel-Angel Perales, MD 212-639-8682
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03531736
Other Study ID Numbers  ICMJE 17-639
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Roni Tamari, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date June 2021

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