Chemotherapy and a Donor Natural Killer Cell Infusion in Treating Patients With Relapsed or Persistent Leukemia or Myelodysplastic Syndrome After a Donor Stem Cell Transplant

NCT00526292 | Completed Phase 2 Results

• 2 other identifiers: 07-035FD-R-004128
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to see if there is a benefit to giving chemotherapy and then natural killer (NK) cells. The NK cells must come from a family member who shares half of the patients HLA proteins. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body. Patients whose blood cancer is not cured with a stem cell transplant do not have standard treatment options. Studies have shown that NK cells from a donor can be given safely and can be helpful in treating some blood diseases. These NK cells are collected from the patients donor and purified using a separation system called CliniMACS that has been used safely in previous studies and is used in this study with the approval of the Federal Food and Drug Administration. The researchers want to find out what effects the NK cells will have on blood cancer and bone marrow function and how to maximize its benefits in treating blood cancers. The researchers hope that giving chemotherapy and then NK cells will be a better treatment for the disease than the current available treatment options. Funding Source - Food and Drug Administration/Office of Orphan Products Development

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; blastic phase chronic myelogenous leukemia; previously treated myelodysplastic syndromes; childhood myelodysplastic syndromes; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; childhood chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22)

Outcome Measures

Primary Outcomes (1)

• Treatment Efficacy as Defined by Complete or Partial Remission

  3 Months following treatment

Study Arms (1)

natural killer (NK) cells with salvage chemotherapy

EXPERIMENTAL

This is a Phase II study, designed to determine the efficacy of natural killer (NK) cells isolated from HLA-haploidentical related donors when infused following a salvage chemotherapy regimen into patients who have relapsed or persistent leukemia following an allogeneic HLA-compatible HSCT and who are ineligible for a second HSCT.

Biological: natural killer cell therapy; Drug: cyclophosphamide; Drug: fludarabine

Interventions

natural killer cell therapy BIOLOGICAL

The patient must be admitted by Day -8 to the Bone Marrow Transplant Service. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor and will be monitored for hematopoietic recovery.

natural killer (NK) cells with salvage chemotherapy

cyclophosphamide DRUG

Day -6 cyclophosphamide 60mg/kg infused over 1 hour (dose adjusted for body weight) for 2 days

natural killer (NK) cells with salvage chemotherapy

fludarabine DRUG

Day -5 fludarabine 25mg/m2 CIV for 5 days

natural killer (NK) cells with salvage chemotherapy

Eligibility Criteria

• Age: Up to 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis and Status
• Patients with a pathologically confirmed diagnosis of relapsed or persistent resistant AML, MDS, or blastic CML following HSCT and who have been deemed ineligible for second HSCT after consideration of adequacy of their physical function, extent of disease, and prior treatment-related toxicities.
• Eligible patients have evidence of disease with ≥5% bone marrow involvement detected by morphology or abnormal cytogenetics (by karyotype or FISH). Patients with molecular detection of markers characteristic of the patient's disease from two consecutive bone marrow biopsies are also eligible. Following diagnosis of relapsed disease, treatment to reduce leukemic burden is allowed prior to protocol therapy without the need for additional disease documentation prior to cyclophosphamide and fludarabine.
• Patients with extramedullary relapse are eligible except for those with CNS involvement.
• Patients must have received an allogeneic HSCT.
• Patient must not be pregnant and must be using adequate form of birth control.
• Patients must have a Karnofsky (adult) or Lansky (pediatric) Performance Status ≥ 60%.
• Hospitalization does not preclude enrollment, as long as the patient's performance status is ≥ 60% according to the KPS grading scale.
• Patients must have adequate physical function measured by :
• Cardiac: asymptomatic and LVEF at rest must be \> 50%. Hepatic: \< 2x ULN ALT and \< 1.5 total serum bilirubin, unless liver is involved with disease, there is congenital benign hyperbilirubinemia, or other reversible causes of hepatic abnormalities are documented.
• Renal: serum creatinine \<1.5 mg/dl or if serum creatinine is outside the normal range, then CrCl \> 50 ml/min Pulmonary: Patient cannot be oxygen-dependent.
• Patients with documented GVHD are not excluded from this trial, but either must not have used systemic immunosuppression for two weeks, or during immunosuppression taper have documented two subtherapeutic levels at least one week apart. Immunosuppressive agents include but are not limited to systemic steroids, calcineurin inhibitors, MTOR-inhibitors, Budesonide, anti-thymocyte globulin. The maximal allowable dose of corticosteroids is the equivalent of 10 mg/day prednisone.
• Patients with grade I/II acute GVHD or limited chronic GVHD and receiving localized GVHD therapy (e.g. topical steroids) are not excluded from this trial.
• Patients having received previous adoptive cellular therapy such as donor lymphocyte infusion (DLI) are not excluded from this trial as long as their disease has been documented to progress within two months of receiving DLI or if the patient has not received DLI within two months of NK cell infusion.
• Patients who have received cytoreductive therapy following documentation of relapse and prior to enrollment are not excluded from this trial. The interval between standard reinduction chemotherapy and start of protocol chemotherapy should be a minimum of 2 weeks, and all induction chemotherapy-related toxicities should be documented to be completely resolved. For patients receiving nonintensive chemotherapies such as hydroxyurea or low-dose cytarabine, nonintensive chemotherapies should be discontinued upon initiation of protocol chemotherapy.

You may not qualify if:

• Patients on systemic immunosuppression with therapeutic drug levels. Patients whose immunosuppression is being actively tapered and have documentation of subtherapeutic drug levels one week apart are not excluded from enrollment. For patients receiving corticosteroids, the maximal allowable dose of corticosteroids is the equivalent of 10 mg/day prednisone.
• Patients with untreated or uncontrolled active infection. Infections that are controlled or being appropriately treated does not exclude a patient from enrollment.
• Donor has cardiac risk factors precluding ability to undergo leukopheresis.
• Donor has evidence of concurrent malignancy or autoimmune disease.
• Donor is pregnant.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Blast Crisis; Congenital Abnormalities

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Katherine Hsu
• Organization: Memorial Sloan Kettering Cancer Center

hsuk@mskcc.org

646-888-2667

Study Officials

• Katherine Hsu, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Ann Alice Jakubowski, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2007
• First Posted: September 10, 2007
• Study Start: August 1, 2007
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: February 12, 2016
• Results First Posted: February 12, 2016

Record last verified: 2016-01

Locations

US (1)