- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03187756
Study of Nonmyeloablative Peripheral Blood Stem Cell Transplant With High-dose Posttransplantation Cyclophosphamide in Hematopoietic Malignancies Including Those That Are Challenging to Engraft
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary Objective Estimate event free survival (EFS) (relapse, progression, or death) rate one year after transplant.
Secondary Objectives:
- Estimate the cumulative incidences of severe acute grade III or higher GVHD, chronic GVHD (overall and by extent)
- Estimate the cumulative incidence of systemic steroid initiation,
- Summarize the graft failure frequency,
- Summarize the kinetics of neutrophil and platelet recovery, and kinetics of donor chimerism in unsorted and CD3+ sorted peripheral blood.
- 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
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
New York
-
New York, New York, United States, 10016
- New York University School of Medicine
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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
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
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.
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1 year
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Number of Major Toxicities and Complications Associated With Transplantation Procedure
Time Frame: 1 year
|
Summarize major toxicities and complications associated with the transplantation procedure
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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
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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
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Site
- Hematologic Diseases
- Neoplasms
- Hematologic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
Other Study ID Numbers
- 17-00042
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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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