Two Step Haplo With Radiation Conditioning

NCT05031897 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 21D.466JT 15545
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experience Treatment-Related Mortality (TRM)

  TRM is defined as death without evidence of recurrent disease in the 2 year period post HSCT. Summarized using Kaplan-Meier curves and the respective Kaplan-Meier estimates of the 2-year event rate are reported as well as their 95% confidence intervals.

  At 2 years post hematopoietic stem cell transplant (HSCT)

Secondary Outcomes (4)

• Development of relapsed disease

  Up to 2 years

• Engraftment

  Up to 2 years

• Immune reconstitution

  Up to 2 years

• Incidence and degree of graft versus host disease (GVHD) after HSCT

  Up to 2 years

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection

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

EXPERIMENTAL

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.

Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection

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

EXPERIMENTAL

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.

Drug: Fludarabine; Radiation: Total-Body Irradiation; Procedure: Donor Lymphocyte Infusion; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Procedure: Hematopoietic Cell Transplantation; Drug: Melphalan; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Diagnostic Imaging; Procedure: Biospecimen Collection

Interventions

Fludarabine DRUG

Given IV

Also known as: 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

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: SCT_TBI, TBI, TOTAL BODY IRRADIATION, Whole Body, Whole Body Irradiation, Whole-Body Irradiation

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Donor Lymphocyte Infusion PROCEDURE

Undergo DLI

Also known as: DLI, Donor Leukocyte Infusion

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Tacrolimus DRUG

Given IV

Also known as: 109581-93-3, FK 506, FK-506, FK506, Fujimycin, Hecoria, Prograf, Protopic, Tacforius

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Mycophenolate Mofetil DRUG

Given IV

Also known as: 115007-34-6, 128794-94-5, Cellcept, MMF

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: HCT, Hematopoietic Stem Cell Infusion, HEMATOPOIETIC STEM CELL TRANSPLANT, Hematopoietic Stem Cell Transplantation, HSCT, SCT, Stem Cell Transplant, stem cell transplantation, NOS

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Melphalan DRUG

Given IV

Also known as: 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

Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration/ biopsy

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Diagnostic Imaging PROCEDURE

Undergo diagnostic imaging

Also known as: Medical Imaging

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm 1: Radiation-Based Cohort (fludarabine, TBI, infusion); Arm 2: Chemotherapy-Based Cohort (fludarabine, melphalan, TBI); Arm 3: HLA- Identical cohort (radiation-based or chemotherapy-based conditioning)

Eligibility Criteria

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

You may qualify if:

• 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.

Sponsors & Collaborators

• Thomas Jefferson University: lead

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadephia, Pennsylvania, 19107, United States

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Anemia, Aplastic; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Thrombocythemia, Essential; Hodgkin Disease; Multiple Myeloma; Myelodysplastic Syndromes; Primary Myelofibrosis; Lymphoma, Non-Hodgkin; Polycythemia Vera

Interventions

fludarabine; fludarabine phosphate; Whole-Body Irradiation; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation; Melphalan; Biopsy; X-Rays; Specimen Handling

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Anemia; Bone Marrow Failure Disorders; Bone Marrow Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing

Study Officials

• Usama Gergis, MD

  Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Usama Gergis, MD

CONTACT

215-503-2455; usama.gergis@jefferson.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: September 2, 2021
• Study Start: October 25, 2021
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2032
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

US (1)