Natural Killer (NK) Cells in Cord Blood Transplantation
This study is currently recruiting participants.
Verified May 2013 by M.D. Anderson Cancer Center
Sponsor:
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01619761
First received: June 12, 2012
Last updated: May 3, 2013
Last verified: May 2013
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
The goal of this clinical research study is to learn if giving cells called natural killer (NK) cells after receiving fludarabine, melphalan, lenalidomide, and a UCB transplant can improve response in patients with CLL. The safety of this treatment and whether NK cells can lessen the risk of graft vs. host disease (GVHD) will also be studied.
The first 3 patients enrolled on this study will not receive NK cells but will receive a cord blood transplant.
UCB and NK cells may be able to kill leukemia cells that remain in your body after chemotherapy treatment.
The UCB cells are also designed to increase blood production and strengthen your immune system.
Fludarabine and melphalan are designed to interfere with the DNA (genetic material) of cancer cells, which may cause the cancer cells to die.
Lenalidomide is being used in this study because it may increase the NK cell activity.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia Chronic Lymphocytic Leukemia |
Drug: Lenalidomide Drug: Fludarabine monophosphate Drug: Melphalan Procedure: NK Infusion Procedure: CB Infusion Drug: Tacrolimus Drug: Mycophenolate mofetil |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Natural Killer Cells In Allogeneic Cord Blood Transplantation |
Resource links provided by NLM:
Drug Information available for:
Melphalan
Melphalan hydrochloride
Fludarabine
Mycophenolic acid
Mycophenolate sodium
Fludarabine phosphate
Tacrolimus
Mycophenolate mofetil hydrochloride
Mycophenolate mofetil
Lenalidomide
U.S. FDA Resources
Further study details as provided by M.D. Anderson Cancer Center:
Primary Outcome Measures:
- Success Rate [ Time Frame: 3 months ] [ Designated as safety issue: No ]Success is ability to generate adequate NK cells in a patient (a minimum of 3x10e8 natural killer (NK) cells). Success Rate is number of participants achieving success divided by total participants.
Secondary Outcome Measures:
- Treatment-Related Mortality (TRM) [ Time Frame: 100 days ] [ Designated as safety issue: No ]100-day treatment-related mortality (TRM) following the methods described by Thall et al.
| Estimated Enrollment: | 13 |
| Study Start Date: | May 2013 |
| Estimated Primary Completion Date: | May 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: CB NK + Chemotherapy
Lenalidomide 10 mg by mouth day -8 to -2. Fludarabine 40 mg/m2 intravenous (IV) from day -7 to -4. Melphalan 140 mg/m2 IV on day -4. The NK cell infusion will be administered intravenously on day -2 over a period of 30 minutes. The NK dose infused will be 5x 106/kg. Remaining cells will be discarded if not needed for laboratory studies. On Day 0, unmanipulated products (smaller cord blood unit and remnant of the larger unit) infused. Tacrolimus 0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no GvHD is present. Mycophenolate mofetil 15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth Days -3 to Day +100 in the absence of GvHD.
|
Drug: Lenalidomide
10 mg by mouth on days -8 to -2.
Other Names:
Drug: Fludarabine monophosphate
40 mg/m2 by vein on days -7 to -4.
Other Names:
Drug: Melphalan
140 mg/m2 by vein on day -4.
Other Name: Alkeran
Procedure: NK Infusion
The NK cell infusion will be administered intravenously on day -2 over a period of 30 minutes. The NK dose infused will be 5x 106/kg. Remaining cells will be discarded if not needed for laboratory studies.
Other Names:
Procedure: CB Infusion
On Day 0, the unmanipulated products (smaller cord blood unit and the remnant of the larger unit) will be infused.
Other Names:
Drug: Tacrolimus
0.03 mg/kg or 0.015 mg/kg (ideal body weight) by vein starting on Day -2 and tapered around Day +180 if no GvHD is present.
Other Name: Prograf
Drug: Mycophenolate mofetil
15 mg/kg (actual body weight with a maximum dose of 1 gram twice daily) by vein or by mouth Days -3 to Day +100 in the absence of GvHD.
Other Names:
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years to 59 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with progressive CLL following standard therapy who meet European Bone Marrow Transplant (EBMT) consensus guidelines of indications for allogeneic stem cell transplantation. This includes patients with (1) lack of response or early relapse within 1 year of receiving a purine analog-containing treatment regimen, (2) disease relapse within 2 years of receiving a purine analog combination therapy or after other therapies such as autologous stem cell transplantation, and (3) CLL associated with p53 mutations or deletions and/or del(17p) requiring therapy. Patients must have chemosensitive disease with at least a PR or SD with last treatment regimen.
- Age less than 60 years of age.
- Performance score of at least 80% by Karnofsky or 0 to 2 ECOG.
- Adequate major organ system function as demonstrated by: a. Left ventricular ejection fraction greater than 45%. b. Pulmonary function test (PFT) demonstrating a diffusion capacity of least 45% predicted. c. Creatinine < 1.6 mg/dL. d. SGPT/bilirubin </= to 2.0 x normal.
- Patients must be informed of the RevAssist® program and mandatory registration as well as be willing and able to comply with its requirements.
- Negative Beta HCG test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization and willing to ongoing pregnancy testing while on treatment with lenalidomide.
- Woman with child bearing potential must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide.
- Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
- Patients must have two CB units available which are matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens. Each cord must contain at least 1.5 x 107 total nucleated cells/Kg recipient body weight (pre-thaw). Cord blood units will be procured through the NMDP (National Marrow Donor Program).
- Have identified a back up cells source in case of engraftment failure. The source can be autologous, related or unrelated.
- Patients who have had a prior autologous transplant are eligible.
Exclusion Criteria:
- Patients with known history of HIV/AIDS.
- Active CNS disease in patient with history of CNS malignancy.
- Patients with chronic active hepatitis or cirrhosis. If positive hepatitis serology, the Study Chair may deem the patient eligible based on the results of liver biopsy.
- Patients with known hypersensitivity to lenalidomide.
- Patients who have a matched related donor who is eligible and willing to donate stem cells.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01619761
Contacts
| Contact: Chitra M. Hosing, MD | 713-792-8750 |
Locations
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
| Principal Investigator: | Chitra M. Hosing, MD | UT MD Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT01619761 History of Changes |
| Other Study ID Numbers: | 2011-0493 |
| Study First Received: | June 12, 2012 |
| Last Updated: | May 3, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by M.D. Anderson Cancer Center:
|
Leukemia Chronic Lymphocytic Leukemia CLL Cord blood CB Umbilical cord blood UCB Natural killer cells NK Graft versus host disease |
GVHD Lenalidomide CC-5013 Revlimid Fludarabine Fludarabine Phosphate Fludara Melphalan Alkeran |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Melphalan Fludarabine Fludarabine monophosphate Lenalidomide Mycophenolic Acid |
Mycophenolate mofetil Tacrolimus Vidarabine Myeloablative Agonists Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antibiotics, Antineoplastic Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013