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Acute Myeloid Leukemia in RemissionPhase 1/2NCT03192397

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

A Phase 1/2 study testing Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate in people with Acute Myeloid Leukemia in Remission and Adult Acute Lymphoblastic Leukemia in Complete Remission, run by Roswell Park Cancer Institute at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide and Fludarabine Phosphate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteUnited States
Study dates
9 Aug 2017to 21 May 2027
Phase
Phase 1/2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 30Show fewer
  • 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.
  • The following are eligible for study inclusion:
  • Patients with MDS/MPN only require <5% myeloblast on bone marrow evaluation.
  • Patients with AML, ALL or CLL may be in CRi, patients with MM may be in VGPR
  • Patients with NHL/HL must be in CR
  • Have a Karnofsky performance status score of > 50%
  • Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% predicted, corrected for hemoglobin and/or alveolar ventilation
  • Left ventricular ejection fraction > 40%
  • Bilirubin =< 3 x upper limit of normal
  • Liver alkaline phosphatase =< 3 x upper limit of normal
  • Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) =< 3 x upper limit of normal
  • Calculated creatinine clearance > 40 cc/min by the modified Cockroft-Gault formula
  • Patient must be cleared pre-transplant by Radiation Oncology to be able to receive 400 cGy
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Patients who have failed a prior autologous or allogeneic transplant are eligible; however, at least 6 months must have elapsed between the start of this reduced intensity conditioning regimen and the last transplant if patient had a prior autologous or myeloablative allogeneic bone marrow transplant (BMT)
  • At least 2 weeks since prior radiation treatment and/or surgery. Appropriate washout of prior chemotherapy per BMT standard of care. If medication is not on the list, go by physician discretion
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase Ib/2 Trial of Fludarabine/Melphalan/Total Body Irradiation With Post Transplant Cyclophosphamide as Graft Versus Host Disease Prophylaxis in Matched-Related and Matched-Unrelated Allogeneic Hematopoietic Cell Transplantation

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the cumulative incidence of extensive chronic graft versus host disease (GVHD) at 1 year after transplantation utilizing the novel conditioning/GVHD prophylactic regimen for patients undergoing allogeneic hematopoietic cell transplantation, in patients who do not progress before day 100.

SECONDARY OBJECTIVES:

  1. To evaluate clinical response, engraftment rate, progression-free survival (PFS) at one year and, overall survival (OS).

II. To determine the cumulative incidence of relapse. III. To evaluate the day 100 transplant-related mortality rate. IV. To determine the cumulative incidence of grade III-IV acute GVHD.

OUTLINE: This is a dose-escalation study of melphalan hydrochloride.

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -5 to -2 and melphalan hydrochloride IV over 30 minutes on day -2. Patients undergo total body irradiation (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 tacrolimus IV and then orally (PO) once tolerated on days 5-180 with a taper beginning on day 100.

After completion of study treatment, patients are followed up for 12 months and then annually thereafter.

Being tested
Allogeneic Hematopoietic Stem Cell Transplantation, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Melphalan Hydrochloride
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Graft vs Host Disease, Hodgkin Disease, Neoplasm, Residual, Myelodysplastic Syndromes, Myeloproliferative Disorders, Lymphoma, Non-Hodgkin, Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allogeneic Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called allogeneic stem cell transplantation, HSC, HSCT

    Undergo allogeneic hematopoietic stem cell transplant

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Melphalan HydrochlorideDrug

    Also called Alkeran, Alkerana, Evomela

    Given IV

  • Mycophenolate MofetilDrug

    Also called Cellcept, MMF

    Given IV

  • SirolimusDrug

    Also called Rapamune

    Given IV and PO

  • Total-Body IrradiationRadiation

    Also called TOTAL BODY IRRADIATION, Whole-Body Irradiation

    Undergo TBI

Study groups in NCT03192397
Study groupRoleWhat they receive
<=50 years of age Cohort AExperimentalCONDITIONING 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.
Receives: 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 BExperimentalPatients 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.
Receives: 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 MelphalanExperimentalFollowing 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.
Receives: 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 MelphalanExperimentalFollowing 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.
Receives: 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 MelphalanExperimentalFollowing 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Extensive Chronic Graft Versus Host Disease (GVHD)

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

    Measured: Up to 365 days

Secondary outcomes (7)

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

    Patients who achieved a clinical response will be summarized descriptively using frequency counts

    Measured: Up to 4 years

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

    Will be analyzed in a descriptive fashion with means +/- standard deviations or frequency counts. Will examine in a post-hoc analysis potential chronic GVHD rates of response by human leukocyte antigen (HLA) matching status.

    Measured: Up to 4 years

  3. Cumulative Incidence of Relapse

    Will be analyzed in a descriptive fashion with frequency counts.

    Measured: Up to 4 years

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

    Will be analyzed in a descriptive fashion with frequency counts.

    Measured: Up to 4 years

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

    Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.

    Measured: Up to 4 years

  6. 1-Year Progression Free Survival (PFS) Rate Assessed as Per Bone Marrow Transplant (BMT) Standard of Care

    Will utilize either straight Kaplan-Meier based estimators or extensions of nonparametric survival models to account for competing risks.

    Measured: At 1 year

  7. Treatment-related Mortality Rates

    Count of participants that died by cohort.

    Measured: All-Cause Mortality monitored/assessed up to 4 years. Adverse Events monitored/assessed from the start date of the conditioning regimen (Day -5) until 30 days after stem cell infusion will be reported, up to 12 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jun 2017
  2. Study start9 Aug 2017
  3. Primary completion21 Aug 2023
  4. Study completion21 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03192397
Sponsor's protocol ID
I 44417
Other IDs
NCI-2017-01069, I 44417
Status last verified
Apr 2026
First submitted
16 Jun 2017
Last updated
14 Apr 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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