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

NCT03531736 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 17-639
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

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.

Conditions

Myeloid Diseases

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Rate of donor Neutrophil Engraftment

  Neutrophil engraftment (recovery of ANC) defined by an ANC ≥ 500/mm\^3 for 3 consecutive days

  30 days post-transplant

Study Arms (1)

Patients with Myeloid Malignancies & Aplastic Anemia

EXPERIMENTAL

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.

Drug: Antithymocyte globulin (Rabbit); Drug: fludarabine; Radiation: total body irradiation; Drug: cyclophosphamide; Drug: Rituxan; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Interventions

Antithymocyte globulin (Rabbit) DRUG

ATG (2 mg/kg/d IV on days-8 through -7)

Also known as: ATG

Patients with Myeloid Malignancies & Aplastic Anemia

fludarabine DRUG

fludarabine (30 mg/m2/d on days -5 through -2)

Patients with Myeloid Malignancies & Aplastic Anemia

total body irradiation RADIATION

TBI 200 cGy (days -2 and -1) given post stem cell infusion

Also known as: TBI

Patients with Myeloid Malignancies & Aplastic Anemia

cyclophosphamide DRUG

cyclophosphamide given post stem cell infusion (50 mg/kg on days +3 and +4)

Patients with Myeloid Malignancies & Aplastic Anemia

Rituxan DRUG

Rituxan (200 mg/m2) will be given to reduce the risk of EBV viremia

Patients with Myeloid Malignancies & Aplastic Anemia

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Patients with Myeloid Malignancies & Aplastic Anemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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
• AML in ≥ 2nd remission
• 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.
• Chronic myelomonocytic leukemia (CMML)
• Chronic myeloid leukemia (CML) with the following features:
• °Patients who have failed or are intolerant to BCR-ABL tyrosine kinase inhibitors.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (2)

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

thymoglobulin; fludarabine; Whole-Body Irradiation; Cyclophosphamide; Rituximab

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roni Tamari, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 9, 2018
• First Posted: May 22, 2018
• Study Start: May 9, 2018
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: August 19, 2025

Record last verified: 2025-08

Locations

US (2)