Chemotherapy, Total Body Irradiation, and Post-Transplant Cyclophosphamide in Reducing Rates of Graft Versus Host Disease in Patients With Hematologic Malignancies Undergoing Donor Stem Cell Transplant

NCT03192397 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: I 44417NCI-2017-01069
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/2 trial studies how well chemotherapy, total body irradiation, and post-transplant cyclophosphamide work in reducing rates of graft versus host disease in patients with hematologic malignancies undergoing a donor stem cell transplant. Drugs used in the chemotherapy, such as fludarabine phosphate and melphalan hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient, they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft versus host disease). Giving cyclophosphamide after the transplant may stop this from happening.

Conditions

Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission; Chronic Myelomonocytic Leukemia in Remission; Graft Versus Host Disease; Hodgkin Lymphoma; Minimal Residual Disease; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Severe Aplastic Anemia; Waldenstrom Macroglobulinemia; Adult Acute Lymphoblastic Leukemia in Complete Remission

Outcome Measures

Primary Outcomes (1)

• Extensive Chronic Graft Versus Host Disease (GVHD)

  Percentage of chronic GVHD of response by human leukocyte antigen (HLA) matching by cohort

  Up to 365 days

Secondary Outcomes (7)

• Clinical Response Assessed as Per Bone Marrow Transplant (BMT) Standard of Care

  Up to 4 years

• Cumulative Incidence of Grade III-IV Acute Graft Versus Host Disease (GVHD)

  Up to 4 years

• Cumulative Incidence of Relapse

  Up to 4 years

• Engraftment Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care

  Up to 4 years

• Overall Survival Assessed as Per Bone Marrow Transplant (BMT) Standard of Care

  Up to 4 years

Study Arms (5)

<=50 years of age Cohort A

EXPERIMENTAL

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and 50mg/m2 melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Radiation: Total-Body Irradiation

<=50 years of age Cohort B

EXPERIMENTAL

Patients receive fludarabine phosphate IV over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo TBI on day -1. Patients recieve 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Radiation: Total-Body Irradiation

>50 years of age Cohort A -25 mg/m2 Melphalan

EXPERIMENTAL

Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2.75 mg/m2 Patients receive 25 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Radiation: Total-Body Irradiation

>50 years of age Cohort B 50 mg/m2 Melphalan

EXPERIMENTAL

Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, Patients receive 50 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Radiation: Total-Body Irradiation

>50 years of age Cohort C .75 mg/m2 Melphalan

EXPERIMENTAL

Following the administration of Fludarabine 40 mg/m2/day on Days -5 to -2, patients receive 75 mg/m2 Melphalan STEM CELL INFUSION: Patients undergo allogeneic hematopoietic stem cell transplant on day 0. GVHD PROPHYLAXIS REGIMEN: Patients receive cyclophosphamide IV over 2 hours on days 3-4, mycophenolate mofetil IV over 2 hours on days 5-35, and sirolimus IV and then PO once tolerated on days 5-180 with a taper beginning on day 100.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Drug: Melphalan Hydrochloride; Drug: Mycophenolate Mofetil; Drug: Sirolimus; Radiation: Total-Body Irradiation

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic hematopoietic stem cell transplant

Also known as: allogeneic stem cell transplantation, HSC, HSCT

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Laboratory Biomarker Analysis OTHER

Correlative studies

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Melphalan Hydrochloride DRUG

Given IV

Also known as: Alkeran, Alkerana, Evomela

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Mycophenolate Mofetil DRUG

Given IV

Also known as: Cellcept, MMF

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Sirolimus DRUG

Given IV and PO

Also known as: Rapamune

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Total-Body Irradiation RADIATION

Undergo TBI

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

<=50 years of age Cohort A; <=50 years of age Cohort B; >50 years of age Cohort A -25 mg/m2 Melphalan; >50 years of age Cohort B 50 mg/m2 Melphalan; >50 years of age Cohort C .75 mg/m2 Melphalan

Eligibility Criteria

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

You may qualify if:

• The patient must have a diagnosis of one of the following (one must be yes):
• Acute myeloid leukemia (AML)
• Acute lymphoblastic leukemia (ALL)
• Chronic lymphoblastic leukemia (CLL)
• Chronic myelogenous leukemia (CML) (chronic phase intolerant or unresponsive to tyrosine kinase inhibitors, accelerated phase, history of blast crisis)
• Myelodysplastic syndrome (MDS)
• Non-Hodgkin lymphoma (NHL)
• Hodgkin lymphoma (HL) (received and failed frontline therapy or failed autologous transplantation or inability to collect enough peripheral blood stem cells \[PBSC\] for autologous hematopoietic cell transplant \[auto-HCT\])
• Multiple myeloma (MM)
• Severe aplastic anemia
• Histocompatible donor identified:
• Related donor matched 5/6 or better (A, B, DRB1)
• Unrelated donor matched 7/8 or better (A, B, C and DRB1)
• Patients with severe aplastic anemia do not have disease requirements; however, if the patient has a mismatched donor, the patient must have had prior therapy with ATG.
• Patients with MDS/MPN only require \<5% myeloblast on bone marrow evaluation.

You may not qualify if:

• Moderate to severe myelofibrosis within 60 days prior to transplant
• Presence of human leukocyte antigen (HLA) antibodies to the donor within 60 days prior to transplant
• Patients who in the opinion of the treating physician are unlikely to comply with the restrictions of allogeneic stem cell transplantation based on formal psychosocial screening. (i.e., serious, uncontrolled psychiatric illness/social situations that would limit compliance with study requirements)
• Uncontrolled diabetes mellitus, cardiovascular disease, active serious infection or other condition which, in the opinion of treating physician, would make this protocol unreasonably hazardous for the patient
• Known human immunodeficiency virus (HIV) positive
• Pregnant or nursing female participants
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study intervention

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Graft vs Host Disease; Hodgkin Disease; Neoplasm, Residual; Myelodysplastic Syndromes; Myeloproliferative Disorders; Lymphoma, Non-Hodgkin; Multiple Myeloma; Anemia, Aplastic; Waldenstrom Macroglobulinemia

Interventions

Cyclophosphamide; fludarabine phosphate; Melphalan; Mycophenolic Acid; Sirolimus; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Macrolides; Lactones; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

• Title: Maureen Ross
• Organization: Roswell Park Cancer Institute

Maureen.Ross@RoswellPark.org

7168451300

Study Officials

• Maureen Ross

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: June 16, 2017
• First Posted: June 20, 2017
• Study Start: August 9, 2017
• Primary Completion: August 21, 2023
• Study Completion (Estimated): May 21, 2027
• Last Updated: April 14, 2026
• Results First Posted: April 14, 2026

Record last verified: 2026-04

Locations

US (1)