Two Step Haplo With Radiation Conditioning

NCT ID: NCT05031897

Last Updated: 2025-10-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

63 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-25

Study Completion Date

2032-04-30

Brief Summary

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This phase II clinical trial evaluates whether a modified modality of conditioning reduces treatment-related mortality (TRM) in patients who undergo a hematopoietic stem cell transplant (HSCT) for a hematological malignancy. HSCT is a curative therapy for many hematopoietic malignancies, however this regimen results in higher rates of TRM than other forms of treatment. In recent years, less intense conditioning regimens with radiation and chemotherapy prior to HSCT have been developed. Radiation therapy uses high energy sources to kill cancer cells and shrink tumors while chemotherapy drugs like fludarabine and cyclophosphamide work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This study evaluates whether a two-step approach with lower-intensity regimens of these treatments prior to HSCT reduces the rate of TRM.

Detailed Description

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PRIMARY OBJECTIVE:

I. To assess the 2 year cumulative incidence of TRM in patients undergoing reduced intensity conditioning (RIC) haploidentical (HI) HSCT in this protocol.

SECONDARY OBJECTIVES:

I. To assess the 2 year cumulative incidence of relapse in patients undergoing RIC HI HSCT in this protocol.

II. To assess the consistency and pace of engraftment. III. To assess the pace of T cell and B cell immune recovery. IV. To assess the incidence and severity of graft versus host disease (GVHD).

OUTLINE: Patients are assigned to 1 of 2 cohorts.

RADIATION-BASED COHORT: Patients receive fludarabine intravenously (IV) on days -11, -10, -9, and -8, undergo total-body irradiation (TBI) twice a day (BID) on days -10 and -9, undergo donor lymphocyte infusion (DLI) on day -6, and receive cyclophosphamide IV on days -3 and -2. Patients begin tacrolimus and mycophenolate mofetil IV on day -1. Patients then undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

CHEMOTHERAPY-BASED COHORT: Patients receive fludarabine IV on days -11, -10, -9, and -8 and melphalan IV on days -10 and -9. Patients undergo TBI and DLI once on day -6. Patients receive cyclophosphamide IV on days -3 and -2 and begin tacrolimus and mycophenolate mofetil on day -1. Patients undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

After completion of study treatment, patients are followed for 2 years.

Conditions

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Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Adult T-Cell Leukemia/Lymphoma Aplastic Anemia Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Essential Thrombocythemia Hematopoietic and Lymphatic System Neoplasm Hodgkin Lymphoma Multiple Myeloma Myelodysplastic Syndrome Myelofibrosis Myeloid Neoplasm Non-Hodgkin Lymphoma Polycythemia Vera Small Lymphocytic Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion)

Patients receive fludarabine IV on days -11, -10, -9, and -8, undergo TBI BID on days -10 and -9, undergo DLI on day -6, and receive cyclophosphamide IV on days -3 and -2. Patients begin tacrolimus and mycophenolate mofetil IV on day -1. Patients then undergo HSCT on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

Given IV

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Donor Lymphocyte Infusion

Intervention Type PROCEDURE

Undergo DLI

Cyclophosphamide

Intervention Type DRUG

Given IV

Tacrolimus

Intervention Type DRUG

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type PROCEDURE

Undergo HSCT

Bone Marrow Aspiration and Biopsy

Intervention Type PROCEDURE

Undergo bone marrow aspiration/ biopsy

Diagnostic Imaging

Intervention Type PROCEDURE

Undergo diagnostic imaging

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI)

Patients receive fludarabine IV on days -11, -10, -9, and -8 and melphalan IV on days -10 and -9. Patients undergo TBI and DLI once on day -6. Patients receive cyclophosphamide IV on days -3 and -2 and begin tacrolimus and mycophenolate mofetil on day -1. Patients undergo hematopoietic stem cell transplant on day 0. Patients undergo bone marrow biopsy/aspiration, imaging and blood sample collection throughout the study.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

Given IV

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Donor Lymphocyte Infusion

Intervention Type PROCEDURE

Undergo DLI

Cyclophosphamide

Intervention Type DRUG

Given IV

Tacrolimus

Intervention Type DRUG

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type PROCEDURE

Undergo HSCT

Melphalan

Intervention Type DRUG

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type PROCEDURE

Undergo bone marrow aspiration/ biopsy

Diagnostic Imaging

Intervention Type PROCEDURE

Undergo diagnostic imaging

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

This group (HLA- Identical cohort), which is expected to be small, can undergo HSCT with radiation-based or chemotherapy-based conditioning. Due to small numbers of patients with available HLA identical related donors, this third, descriptive arm is included so that this group, too small in number for a free-standing study, are treated on clinical trial. This is also a separate arm of the study and the outcome of patients treated on this arm will be analyzed descriptively without statistical comparison or power analysis.

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

Given IV

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Donor Lymphocyte Infusion

Intervention Type PROCEDURE

Undergo DLI

Cyclophosphamide

Intervention Type DRUG

Given IV

Tacrolimus

Intervention Type DRUG

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type PROCEDURE

Undergo HSCT

Melphalan

Intervention Type DRUG

Given IV

Bone Marrow Aspiration and Biopsy

Intervention Type PROCEDURE

Undergo bone marrow aspiration/ biopsy

Diagnostic Imaging

Intervention Type PROCEDURE

Undergo diagnostic imaging

Biospecimen Collection

Intervention Type PROCEDURE

Undergo blood sample collection

Interventions

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Fludarabine

Given IV

Intervention Type DRUG

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Donor Lymphocyte Infusion

Undergo DLI

Intervention Type PROCEDURE

Cyclophosphamide

Given IV

Intervention Type DRUG

Tacrolimus

Given IV

Intervention Type DRUG

Mycophenolate Mofetil

Given IV

Intervention Type DRUG

Hematopoietic Cell Transplantation

Undergo HSCT

Intervention Type PROCEDURE

Melphalan

Given IV

Intervention Type DRUG

Bone Marrow Aspiration and Biopsy

Undergo bone marrow aspiration/ biopsy

Intervention Type PROCEDURE

Diagnostic Imaging

Undergo diagnostic imaging

Intervention Type PROCEDURE

Biospecimen Collection

Undergo blood sample collection

Intervention Type PROCEDURE

Other Intervention Names

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2-Fluoro-9-beta-arabinofuranosyladenine 2-Fluorovidarabine 21679-14-1 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine 9-Beta-D-arabinofuranosyl-2-fluoroadenine Fluradosa SCT_TBI TBI TOTAL BODY IRRADIATION Whole Body Whole Body Irradiation Whole-Body Irradiation DLI Donor Leukocyte Infusion (-)-Cyclophosphamide 1-bis(2-chloroethyl)-amino-1-oxo-2-aza-5-oxaphosphoridin monohydrate 2-[bis(2-chloroethyl)amino]tetrahydro-2H-1,3,2-oxazaphosphorine 2-oxide monohydrate 2-[bis(b-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane-2-oxide monohydrate 2-[di(chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide monohydrate 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate 6055-19-2 Asta B 518 B 518 B-518 B518 bis(2-chloroethyl)phosphamide cyclic propanolamide ester monohydrate Bis(2-chloroethyl)phosphoramide cyclic propanolamide ester monohydrate Carloxan Ciclofosfamida Ciclofosfamide Cicloxal Clafen Claphene CP monohydrate CTX CYCLO-cell Cycloblastin Cycloblastine Cyclophospham Cyclophosphamid monohydrate Cyclophosphamide Monohydrate Cyclophosphamidum Cyclophosphan Cyclophosphane Cyclophosphanum Cyclostin Cytophosphan Cytophosphane Cytoxan Fosfaseron Genoxal Genuxal Ledoxina Mitoxan N,N-bis(2-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate N,N-bis(2-chloroethyl)-N'-(3-hydroxypropyl)phosphorodiamidic acid intramolecular ester monohydrate, N,N-bis(2-chloroethyl)tetrahydro-2H-1,3,2-oxazaphosphorin-2-amine 2-oxide monohydrate N,N-bis(b-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate N,N-bis(beta-chloroethyl)-N',O-propylenephosphoric acid ester diamide monohydrate N,N-bis(beta-chloroethyl)-N',O-trimethylenephosphoric acid ester diamide monohydrate Neosar Revimmune Syklofosfamid WR 138719 WR- 138719 WR-138719 WR138719 109581-93-3 FK 506 FK-506 FK506 Fujimycin Hecoria Prograf Protopic Tacforius 115007-34-6 128794-94-5 Cellcept MMF HCT Hematopoietic Stem Cell Infusion HEMATOPOIETIC STEM CELL TRANSPLANT Hematopoietic Stem Cell Transplantation HSCT SCT Stem Cell Transplant stem cell transplantation NOS 148-82-3 4-[bis(2-chloroethyl)amino]-L-phenylalanine Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalan for Injection-Hepatic Delivery System Melphalanum p-di(chloroethyl)amino-L-phenylalanine Phenylalanine Mustard Phenylalanine nitrogen mustard Sarcoclorin Sarkolysin WR-19813 Medical Imaging Biological Sample Collection Biospecimen Collected Specimen Collection

Eligibility Criteria

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Inclusion Criteria

* Radiation-based cohort diagnoses:

* Acute myeloid leukemia
* Acute lymphoid leukemia in remission
* Myelodysplasia (MDS)
* Chronic lymphocytic leukemia (CLL) with no or minimal lymph node involvement
* Multiple myeloma
* Chronic myeloid leukemia
* Myelofibrosis
* Myeloid malignancy not otherwise specified
* Chronic myelomonocytic leukemia
* Essential thrombocytopenia or polycythemia vera
* T cell leukemia
* T cell lymphoma without significant lymph node disease burden
* Any hematological malignancy or dyscrasia not cited above in which HSCT is potentially curable
* Any patient who has a hematological disease that would normally be treated on a myeloablative study, but is prevented from doing so by factors in their past medical history. Examples are patients with previous treatment with radiation therapy precluding total-body irradiation (TBI), or a past history of myeloablative therapy, precluding a 2nd myeloablative regimen.
* Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered)
* Chemotherapy-based cohort diagnoses:

* Hodgkin or non-Hodgkin lymphoma
* Small lymphocytic lymphoma/CLL
* Any other diagnosis in which chemotherapy is thought to be superior to radiotherapy for treatment of the disease
* Hematological malignancy in patients who cannot receive \> 2 Gy radiation
* Aplastic anemia and other non-malignant hematologic dyscrasias
* Patients must have a donor who is one-haplotype mismatched (number of mismatches in either direction not considered)
* Human leukocyte antigen (HLA) identical cohort diagnoses:

\* Patients in this group will be treated in parallel to the radiation-based cohort or the chemotherapy-based group based on what category their diagnosis falls into. However, these patients will have HLA identical related donors (one-antigen cross-over event included).
* Left ventricular ejection fraction of \>= 50%
* Diffusion lung capacity of oxygen \>= 50% and forced expiratory volume at 1 second \>= 50% of predicted corrected for hemoglobin
* Serum bilirubin =\< 1.8
* Aspartate aminotransferase or alanine aminotransferase =\< 2.5 x upper limit of normal
* Creatinine clearance of \>= 60 mL/min
* Patients must have adequate Karnofsky performance status (KPS) and Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores:

* Patients \< age 60 years must have a KPS of \>= 60% and an HCT-CI score of 5 or less
* Patients aged 60 to 65 years must have a KPS of \>= 60% and an HCT-CI score of 4 or less
* Patients aged 66 to 69 years must have a KPS of 90% and an HCT-CI score of 3 or less
* Patients aged 70 years or more must have a KPS of 90% and an HCT-CI score of 2 or less
* (Patients with greater than the allowable HCT-CI points for age can be enrolled for trial with approval of the principal investigator (PI) and at least 1 co-investigator (CI) not on the primary care team of the patient). This is an adjustment to account for healthy patients who meet the spirit of this protocol but have histories that result in higher than guideline HCT-CI points. An example is a patient with a solid tumor malignancy in their remote history (adds 3 points to HCT-CI total) where the treatment for the malignancy occurred years to decades before and there has been complete recovery of toxicities
* Patients must be willing to use contraception if they have childbearing potential
* Patient or patient's guardian is able to give informed consent
* Patients should have a life expectancy of \>= 6 months for reasons other than their underlying hematologic/oncologic disorder
* Patients with evidence of another malignancy, exclusive of a skin cancer that requires only local treatment, should not be enrolled on this protocol
* Patients should not be:

* Human immunodeficiency virus positive
* Have active involvement of the central nervous system with malignancy. This can be documented by a normal neurological exam, magnetic resonance imaging (MRI) of the head, and/or a negative cerebral spinal fluid analysis
* Pregnant or breastfeeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Thomas Jefferson University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Usama Gergis, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

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Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadephia, Pennsylvania, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Usama Gergis, MD

Role: CONTACT

215-503-2455

Facility Contacts

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Usama Gergis, MD

Role: primary

215-503-2455

Other Identifiers

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JT 15545

Identifier Type: OTHER

Identifier Source: secondary_id

21D.466

Identifier Type: -

Identifier Source: org_study_id

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