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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

NCT03531736

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasm
  • Myeloproliferative Neoplasm
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 17-639
  • NCT ID: NCT03531736

Conditions

  • Myeloid Diseases

Interventions

DrugSynonymsArms
Antithymocyte globulin (Rabbit)ATGPatients with Myeloid Malignancies & Aplastic Anemia
fludarabinePatients with Myeloid Malignancies & Aplastic Anemia
cyclophosphamidePatients with Myeloid Malignancies & Aplastic Anemia
RituxanPatients with Myeloid Malignancies & Aplastic Anemia

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Patients with Myeloid Malignancies & Aplastic AnemiaExperimentalTransplant 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.
  • Antithymocyte globulin (Rabbit)
  • fludarabine
  • cyclophosphamide
  • Rituxan

Eligibility Criteria

        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 >50ml/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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Rate of donor Neutrophil Engraftment
Time Frame:30 days post-transplant
Safety Issue:
Description:Neutrophil engraftment (recovery of ANC) defined by an ANC ≥ 500/mm^3 for 3 consecutive days

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Allogeneic Hematopoietic Stem Cell Transplantation
  • intensity conditioning regimen
  • 17-639

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