Hematologic MalignanciesPhase 1NCT04098393
Giving Chemotherapy for a Shortened Amount of Time Before a Stem Cell Transplantation
A Phase 1 study testing Busulfan 3.2 mg/kg/day, Fludarabine and Melphalan in people with Hematologic Malignancies, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
The purpose of this study is to see if a condensed version of the chemotherapy regimen busulfan, melphalan, fludarabine (bu/mel/flu) and the drug antithymocyte globulin (ATG-also referred to as rATG or thymoglobulin) can have the same or fewer number of severe side effects in people with various blood cancers 30 days… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematologic Malignancies
- What is being tested?
- Busulfan 3.2 mg/kg/day, Fludarabine and Melphalan
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Sep 2019to Sep 2027
- Phase
- Phase 1
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
- Patients aged ≥ 18 years old.
- Patients with any of the following hematologic malignancies for which allo-HCT is indicated, including:
- Acute myeloid leukemia (AML) with intermediate or high-risk features in CR1.
- Relapsed AML in ≥ CR2.
- Acute leukemias of ambiguous lineage in ≥ CR1.
- Acute lymphoid leukemia (ALL) in CR1 with clinical, flow cytometric, or molecular features indicating a high risk for relapse, or ALL in ≥ CR2.
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- CML meeting one of the following criteria:
- Failed response to or intolerant to BCR-ABL tyrosine kinase inhibitors (TKIs).
- CML with BCR-ABL mutation consistent with poor response to TKIs (e.g., T315I mutation)
- CML in accelerated phase or blast crisis with <10% blasts after therapy, or in second chronic phase.
- Myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), or MDS/MPN overlap syndromes with least one of the following:
- Revised International Prognostic Scoring System risk score of intermediate or higher at the time of transplant evaluation.
- Life-threatening cytopenias.
- 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.
- Therapy related disease or disease evolving from other malignant processes.
- Chronic myelomonocytic leukemia (CMML-1 or CMML-2).
- Severe aplastic anemia.
- Relapsed Hodgkin lymphoma meeting both of the following criteria:
- Responding to therapy prior to enrollment.
- Relapse after autologous HCT or are ineligible for autologous HCT.
- Relapsed non-Hodgkin lymphoma meeting both of the following criteria:
- Responding to therapy prior to enrollment.
- Relapse after prior autologous HCT or are ineligible for autologous HCT.
- High-risk multiple myeloma following autologous HCT or relapsed multiple myeloma following autologous HCT with chemosensitive disease.
- Adequate organ function is required, defined as follows:
- Serum bilirubin ≤ 2 mg/dL, unless benign congenital hyperbilirubinemia. Patients with hyperbilirubinemia related to paroxysmal nocturnal hemoglobinuria or other hemolytic disorders are eligible with PI approval.
- AST, ALT, and alkaline phosphatase < 3 times the upper limit of normal unless thought to be disease-related.
- Creatinine clearance ≥ 50 ml/min (calculated by Cockcroft Gault)
- LVEF ≥ 45% by MUGA or resting echocardiogram.
- Pulmonary function (FEV1 and corrected DLCO) ≥ 50% predicted.
- Adequate performance status of ECOG ≤ 2.
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
Who cannot join
- Patients with active extramedullary disease.
- Patients with active central nervous system malignancy.
- Active and/or uncontrolled infection at the time of allo-HCT.
- Patients who have undergone previous allo-HCT.
- Patients who have undergone previous autologous HCT within the last 6 months, with the exclusion of high-risk multiple myeloma patients.
- Patient seropositivity for HIV I/II and/or HTLV I/II.
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- Females who are pregnant or breastfeeding.
- Patients unwilling to use contraception during the study period.
- Patient or guardian unable to give informed consent or unable to comply with the treatment protocol.
- Donor Inclusion and Exclusion Criteria:
- Must be a 10/10 HLA genotypically matched related or unrelated donor at 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: A Pilot Study of Condensed Busulfan, Melphalan, and Fludarabine Conditioning Prior to Ex-vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation
The purpose of this study is to see if a condensed version of the chemotherapy regimen busulfan, melphalan, fludarabine (bu/mel/flu) and the drug antithymocyte globulin (ATG-also referred to as rATG or thymoglobulin) can have the same or fewer number of severe side effects in people with various blood cancers 30 days after they receive an allogeneic hematopoietic cell transplantation.
- Conditions
- Hematologic Malignancies
- Being tested
- Busulfan 3.2 mg/kg/day, Fludarabine, Melphalan, Antithymocyte globulin (ATG), Busulfan 0.8 mg/kg
- Keywords
- Busulfan, Melphalan, Fludarabine, Allogeneic Hematopoietic Cell Transplantation, 19-245
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Busulfan 3.2 mg/kg/dayDrug
Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels.
FludarabineDrug
Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2.
MelphalanDrug
Melphalan (70mg/m2/day) administered on days -6 and -5.
Antithymocyte globulin (ATG)Drug
ATG will be given based on a dynamic nomogram based on the patient's absolute lymphocyte count at the start of conditioning and can result in 2 or 3 days of ATG administration.
Busulfan 0.8 mg/kgDrug
Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels.
Allogeneic hematopoietic cell transplantation (Allo-HCT)Procedure or surgery
Allogeneic hematopoietic cell transplantation following the conditioning regimen.
| Study group | Role | What they receive |
|---|---|---|
| patients hematologic malignancies other than multiple myeloma | Experimental | A. Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels. B. Melphalan (70mg/m2/day) administered on days -6 and -5. C. Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis. Receives: Drug: Busulfan 3.2 mg/kg/day; Drug: Fludarabine; Drug: Melphalan; Drug: Antithymocyte globulin (ATG); Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT) |
| patients with multiple myeloma | Experimental | A. Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels. B. Melphalan (70 mg/m2/day) administered on days -6 and -5. C. Fludarabine (25 mg/m2/day) administered on days -6, -5, -4, -3, -2. All patients receiving matched related or unrelated donor allografts receive anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2 to deplete chemotherapy resistant host T-cells that could hinder engraftment, and it may provide additional GVHD prophylaxis. Receives: Drug: Fludarabine; Drug: Melphalan; Drug: Antithymocyte globulin (ATG); Drug: Busulfan 0.8 mg/kg; Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
the number of grade 4 toxicities
All grade 4 CTCAEv5.0 toxicities are included except for hematologic toxicities that are considered expected for patients receiving myeloablative conditioning.
Measured: in the first 30 days post-HCT
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2019
- Study start18 Sep 2019
- Primary completionSep 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a pilot study in which adult patients with hematologic malignancies undergoing ex-vivo CD34-selected allo-HCT will receive a condensed version of our standard bu/mel/flu regimen, reducing the length of the conditioning regimen from 8 days to 5 days.
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michael Scordo, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04098393
- Sponsor's protocol ID
- 19-245
- Status last verified
- Oct 2026
- First submitted
- 19 Sep 2019
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.