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Giving Chemotherapy for a Shortened Amount of Time Before a Stem Cell Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04098393
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : June 9, 2020
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief 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 after they receive an allogeneic hematopoietic cell transplantation.

Condition or disease Intervention/treatment Phase
Hematologic Malignancies Drug: Busulfan 3.2 mg/kg/day Drug: Fludarabine Drug: Melphalan Drug: Antithymocyte globulin (ATG) Drug: Busulfan 0.8 mg/kg Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT) Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment
Official Title: A Pilot Study of Condensed Busulfan, Melphalan, and Fludarabine Conditioning Prior to Ex-vivo CD34+ Selected Allogeneic Hematopoietic Cell Transplantation
Actual Study Start Date : September 18, 2019
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: patients hematologic malignancies other than multiple myeloma
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.
Drug: Busulfan 3.2 mg/kg/day
Busulfan 3.2 mg/kg/day, with dose adjustments made according to pharmacokinetic (PK) levels.

Drug: Fludarabine
Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2.

Drug: Melphalan
Melphalan (70mg/m2/day) administered on days -6 and -5.

Drug: Antithymocyte globulin (ATG)
Anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2

Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT)
Allogeneic hematopoietic cell transplantation following the conditioning regimen.

Experimental: patients with multiple myeloma
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.
Drug: Fludarabine
Fludarabine (25mg/m2/ day) administered on days -6, -5, -4, -3, and -2.

Drug: Melphalan
Melphalan (70mg/m2/day) administered on days -6 and -5.

Drug: Antithymocyte globulin (ATG)
Anti-thymocyte globulin (ATG) 2.5 mg/kg/day on days -3 and -2

Drug: Busulfan 0.8 mg/kg
Busulfan 0.8 mg/kg every 6 hours x 10 doses, with dose adjustments made according to PK levels.

Procedure: Allogeneic hematopoietic cell transplantation (Allo-HCT)
Allogeneic hematopoietic cell transplantation following the conditioning regimen.




Primary Outcome Measures :
  1. the number of grade 4 toxicities [ Time Frame: in the first 30 days post-HCT ]
    All grade 4 CTCAEv5.0 toxicities are included except for hematologic toxicities that are considered expected for patients receiving myeloablative conditioning.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
    • 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.

Exclusion Criteria:

  • 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04098393


Contacts
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Contact: Michael Scordo, MD 212-639-6052 scordom@mskcc.org
Contact: Roni Tamari, MD 212-639-5987

Locations
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United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Michael Scordo, MD    212-639-6052      
Contact: Roni Tamari, MD    212-639-5987      
Principal Investigator: Michael Scordo, MD         
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
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Principal Investigator: Michael Scordo, MD Memorial Sloan Kettering Cancer Center
Additional Information:
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Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04098393    
Other Study ID Numbers: 19-245
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: June 9, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Busulfan
Melphalan
Fludarabine
Allogeneic Hematopoietic Cell Transplantation
19-245
Additional relevant MeSH terms:
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Hematologic Neoplasms
Neoplasms
Neoplasms by Site
Hematologic Diseases
Fludarabine
Melphalan
Busulfan
Antilymphocyte Serum
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists