Clinical trial NCT01392989: Post T-plant Infusion of Allogeneic Cytokine Induced Killer (CIK) Cells as Consolidative Therapy in Myelodysplastic Syndromes/Myeloproliferative Disorders
Official title: Post Transplant Infusion of Allogeneic Cytokine Induced Killer Cells as Consolidative Therapy After Non-Myeloablative Allogeneic Transplantation in Patients With Myelodysplasia or Myeloproliferative Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neural Tube Defects
Anemia
Leukemia, Myeloid
Bone Marrow Transplant Failure
Myelodysplastic Syndromes (MDS)
Myeloproliferative Disorders
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2011-07-13
Enrollment: 44
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Allogeneic stem cell transplantation (transplant of blood cells from another individual) is a treatment option for patients with myelodysplasia or myeloproliferative Disorders. During the course of this study, it will be evaluated whether a particular type of blood cell, called a cytokine-induced killer (CIK) cell, may add benefit to allogeneic stem cell transplantation. CIK cells are present in small quantities in the bloodstream but their numbers can be expanded after a brief period of nurturing in a laboratory.

Detailed description: Primary Objectives:

To determine the rate of conversion to FDC following infusion of allogeneic CIK cells among patients with MDS, therapy-related myeloid neoplasms, or MPD who receive non myeloablative preparative regimen of TLI / ATG followed by allogeneic HCT and consolidation with allogeneic CIK cells.

Secondary Objectives:

* To determine the 2 year overall survival (OS) and event free survival (EFS)
* To determine the incidence of acute GVHD following infusion of allogeneic CIK cells
* To assess the pre-transplant expression of NKG2D ligands in patients' bone marrow aspirates.

Eligibility criteria: INCLUSION CRITERIA, RECIPIENT WITH MYELODYSPLASTIC SYNDROME (MDS)

* Diagnosis of MDS classifiable by the World Health Organization (WHO) on the basis of:

  * Refractory anemia
  * Refractory anemia with excess blasts-1
  * Refractory anemia with excess blasts-2
  * Refractory cytopenia with multi-lineage dysplasia
  * Refractory cytopenia with multi-lineage dysplasia and ringed sideroblasts
  * Chronic myelomonocytic leukemia (CMML)
  * MDS transformed to acute leukemia
  * MDS-unclassified
* Participants with advanced MDS must have \< 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.
* Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia free-state (MLFS) with blasts \< 5%

INCLUSION CRITERIA, RECIPIENT WITH MYELOPROLIFERATIVE DISORDER (MPD)

* Diagnosis of MPD on the basis of:

  * Idiopathic myelofibrosis
  * Polycythemia vera
  * Essential thrombocythemia
  * Chronic myelomonocytic leukemia (CML)
  * CML, Philadelphia chromosome-negative
  * Chronic neutrophilic leukemia
  * Chronic eosinophilic leukemia
  * Hypereosinophilic cyndrome
  * Systemic mastocytosis
* \< 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.
* Participants with evolution to acute leukemia (AML) must be in a morphologic leukemia free-state (MLFS) with blasts \< 5%. Presence of residual dysplastic features following cytoreductive therapy is acceptable.

INCLUSION CRITERIA, RECIPIENT WITH THERAPY-RELATED MYELOID NEOPLASM (t MDS)

* \< 10% marrow blasts prior to receiving conditioning with TLI/ATG, documented by marrow examination within 1 month prior.
* Morphologic leukemia free-state with blasts \< 5 %.
* Age \> 50 years, or \< 50 years of age but at high-risk for regimen-related toxicity associated with conventional myeloablative transplants due to pre-existing medical conditions or prior therapy
* Availability of a fully HLA-matched or single antigen/allele mismatched sibling or unrelated donor
* Prior malignancy diagnosed \> 5 years ago without evidence of disease, or \< 5 years ago with life expectancy of \> 5 years are eligible (prior malignancy is not a requirement)

INCLUSION CRITERIA, DONOR

* Donors must be HLA-matched or one allele mismatched.
* Donor age \< 75 (EXCEPTION by Principal Investigator discretion)
* Must consent to PBSC mobilization with G-CSF; apheresis; and collection and donation of plasma
* Donor must consent to placement of a central venous catheter in the event that peripheral venous access is limited.

EXCLUSION CRITERIA, RECIPIENT

Any of the following:

* Uncontrolled CNS involvement with disease
* Pregnant
* Cardiac function: ejection fraction (EF) \< 35% or uncontrolled cardiac failure
* Diffusing capacity of the lungs for carbon monoxide (DLCO) \< 40% predicted
* Bilirubin \> 3 mg/dL
* Aspartate aminotransferase (AST) \> 3x the upper limit of normal (ULN)
* Alanine aminotransferase (ALT) \> 3x ULN
* Estimated creatinine clearance \< 50 mL/min
* Karnofsky performance score (KPS) \< 70%
* Documented fungal disease that is progressive despite treatment
* HIV-positive

EXCLUSION CRITERIA, DONOR

Any of the following:

* Identical twin to recipient
* Pregnant or lactating
* Prior malignancy within the preceding 5 years (EXCEPTION: non-melanoma skin cancers)
* HIV seropositivity

Primary outcomes:
measure: Full Donor Chimerism (FDC)
timeFrame: 90 days
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Event-free Survival (EFS) Rate
timeFrame: 2 years
measure: Number of Participants That Experience Grade 2 to 4 aGvHD Within 100 Days and 1 Year
timeFrame: 1 year
measure: Pre-transplant Expression of Natural-killer Group 2, Member D (NKG2D) Ligands
timeFrame: Pre-transplant
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Everett Meyer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Narayan R, Benjamin JE, Shah O, Tian L, Tate K, Armstrong R, Xie BJ, Lowsky R, Laport G, Negrin RS, Meyer EH. Donor-Derived Cytokine-Induced Killer Cell Infusion as Consolidation after Nonmyeloablative Allogeneic Transplantation for Myeloid Neoplasms. Biol Blood Marrow Transplant. 2019 Jul;25(7):1293-1303. doi: 10.1016/j.bbmt.2019.03.027. Epub 2019 Apr 3.