Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft

March 16, 2020 updated by: NYU Langone Health

Phase II Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft

This is an open label phase II single arm study of peripheral blood stem cell transplantation and posttransplantation cyclophosphamide, using HLA full match or haploidentical related donors, in hematological malignancies including those difficult to engraft. The objective of this study is to evaluate the safety and feasibility in nonmyeloablative, partially HLA-mismatched or HLA-matched PBSC transplant from haploidentical donors or fully matched donors with post-grafting immunosuppression that includes high-dose cyclophosphamide, tacrolimus, and Mycophenolate mofetil (MMF).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Primary Objective Estimate event free survival (EFS) (relapse, progression, or death) rate one year after transplant.

Secondary Objectives:

  1. Estimate the cumulative incidences of severe acute grade III or higher GVHD, chronic GVHD (overall and by extent)
  2. Estimate the cumulative incidence of systemic steroid initiation,
  3. Summarize the graft failure frequency,
  4. Summarize the kinetics of neutrophil and platelet recovery, and kinetics of donor chimerism in unsorted and CD3+ sorted peripheral blood.
  5. Summarize major toxicities and complications associated with the transplantation procedure selected toxicities.

Exploratory Objectives:

Explore the association between the amount of donor T cell chimerism at ~ Day 28 and patient/graft characteristics (e.g., prior therapies, graft cell dose) and transplantation outcomes (sustained engraftment, relapse or progression, GVHD).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
6

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • New York University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

The following are eligibility for study entry and transplantation.

  • Presence of a suitable related, HLA-haploidentical or HLA-matched stem cell donor
  • The donor and recipient must be identical at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum match of 5/10 is therefore required for related donors, and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
  • Eligible diagnoses:
  • Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia [CMML] with at least one poor risk factor
  • No active extramedullary leukemia or known active CNS involvement by malignancy. Such disease treated into remission is permitted.
  • Any previous autologous HSCT must have occurred at least 3 months prior to start of conditioning
  • No previous allogeneic HSCT
  • Adequate end-organ function Note: Infection is permitted if there is evidence of response to medication. Eligibility of HIV infected patients will be determined on a case-by-case basis.
  • ECOG performance status < 2 or Karnofsky or Lansky score > 60.
  • Age > 18 years and older.
  • Not pregnant or breast-feeding.
  • No uncontrolled infection.

Eligible diagnoses:

  • Myelodysplastic syndrome (MDS) including chronic myelomonocytic leukemia [CMML] with at least one of the following poor-risk features

  • SLL or CLL with 17p deletion, or with progression < 6 months after second or greater treatment regimen. Must have the following to be an acceptable candidate as well:

    • < 20% of bone marrow cellularity involved by SLL/CLL (to lower risk of graft rejection)
    • No lymph nodes > 5 cm in any dimension
    • No massive splenomegaly, defined as > 6 cm below the left costal margin
  • T-cell PLL in PR or better prior to transplantation. Must also have < 20% of bone marrow cellularity involved by PLL (to lower risk of graft rejection).
  • Interferon- or tyrosine kinase-refractory CML in first chronic phase, TKI-intolerant CML in first chronic phase, or CML in second or subsequent chronic phase

  • Philadelphia chromosome negative myeloproliferative disease (including myelofibrosis)

    o Intermediate-2 or High risk score by DIPSS Plus is required for a diagnosis of myelofibrosis

  • Multiple myeloma or plasma cell leukemia with a PR or better to the last treatment regimen, based on the International Myeloma Working Group (IMWG) criteria.49
  • Hematologic malignancy in complete remission with minimal residual disease (MRD) non detectable OR detectable by conventional cytogenetics, FISH, flow cytometry, or molecular testing or hematologic malignancies in partial remission

Donor eligibility

  • Donors must be either:
  • HLA-haploidentical or HLA-identical relatives of the patient based on allele or allele group level typing as defined in Section 4.1.
  • Medically fit to and willing to donate
  • Lack of recipient anti-donor HLA antibody
  • Has not donated blood products to patient

Exclusion Criteria:

  • Any individual that does not meet the eligibility criteria for transplantation or donor eligibility will not be a part of this trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cyclophosphamide
Drug: Cyclophosphamide
Shortened duration immunosuppression following nonmyeloablative peripheral blood stem cell transplant with high dose post transplantation cyclophosphamide in malignancies to engraft.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Event Free Survival (EFS)
Time Frame: One Year
Estimate the one year after transplantation event free survival (EFS) rate using a Kaplan-Meier curve with a 90% confidence interval. An event for EFS is defined as the first of any of the following failures: relapse or disease progression or death from any cause
One Year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Chronic GVHD and Grades I-IV GVHD
Time Frame: 1 year
Acute GVHD is graded by standard criteria, and all suspected cases of acute GVHD will be confirmed histologically by biopsy of an affected organ. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I is characterized as mild disease (skin involvement alone), Grade II as moderate, Grade III as severe (involvement of any organ system), and Grade IV as life-threatening. The diagnosis of a chronic GVHD per NIH criteria requires a) at least 1 diagnostic manifestation or b) 1 distinctive manifestation confirmed by biopsy or testing of the same or other involved organ.
1 year
Number of Major Toxicities and Complications Associated With Transplantation Procedure
Time Frame: 1 year
Summarize major toxicities and complications associated with the transplantation procedure
1 year
Cumulative Incidences of Systemic Steroid Initiation
Time Frame: 1 year
Estimate the cumulative incidence of systemic steroid initiation, by 1 year after HSCT. This is will be reported as number of participants who started steroids over the course of the study.
1 year
Graft Failure Frequency
Time Frame: 1 year
Graft failure and death, or graft failure, death and treatment of relapse/progressions. This will be reported as the number of participants with graft failures.
1 year
Time to Neutrophil Recovery
Time Frame: 1 year
Neutrophil recovery is defined as post-nadir ANC greater than or equal to 500/mm3 for three consecutive measurements on different days. The first of the three days will be designated as the day of neutrophil recovery.
1 year
Time to Platelet Recovery
Time Frame: 1 year
Platelet recovery is defined as sustained platelet count greater than or equal to 20,000/mm3 or greater than or equal to 50,000/mm3 with no platelet transfusions in the preceding seven days. The first of three consecutive measurements on different days will be designated as the day of initial platelet recovery.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 2, 2017

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 18, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 18, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 2, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 15, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 16, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-00042

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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