Phase 2
Completed N=41
Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation, and Donor Bone Marrow Transplant Followed by Donor Natural Killer Cell Therapy, Mycophenolate Mofetil, and Tacrolimus in Treating Patients With Hematologic Cancer
Acute Lymphoblastic Leukemia · Acute Myeloid Leukemia · Non-Hodgkin's Lymphoma · Diffuse Large B-Cell Lymphoma
Source: ClinicalTrials.gov NCT00789776 ↗
Enrolled (actual)
41
Serious AEs
2.5%
Results posted
Jul 2018
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities — 0; 0 Participants
Summary
This phase I/II trial studies the side effects and best dose of donor natural killer (NK) cell therapy and to see how well it works when given together with fludarabine phosphate, cyclophosphamide, total-body irradiation, donor bone marrow transplant, mycophenolate mofetil, and tacrolimus in treating patients with hematologic cancer. Giving chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation before a donor bone marrow transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving an infusion of the donor's T cells (donor lymphocyte infusion) may help the patient's immune system see any remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving mycophenolate mofetil and tacrolimus after the transplant may stop this from happening.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities |
0; 0 | — |
| PRIMARY Number of Participants With Relapsed Disease |
1; 10 | — |
| PRIMARY Number of Participants With Grades III-IV Acute GVHD |
1; 0 | — |
| PRIMARY Number of Non-relapse Participant Mortalities |
0; 0 | — |
| PRIMARY Number of Participants Who Experienced Graft Failure |
0; 4 | — |
| SECONDARY Number of Subjects Surviving Post-transplant. |
5; 25 | — |
| SECONDARY Number of Participants Who Experienced Chronic Extensive GVHD |
2; 3 | — |
Eligibility Criteria
Inclusion Criteria
- Patients with the following hematologic malignancies will be permitted although other diagnoses can be considered if approved by Patient Care Conference (PCC) and the principal investigators:
- Aggressive non-Hodgkin lymphomas (NHL) and other histologies such as diffuse large B cell (DLBC) NHL - a) not eligible for autologous HCT, b) not eligible for high-dose HCT, c) after failed autologous HCT, or d) be part of a tandem auto-allo approach for high risk patients
- Mantle cell NHL must be beyond first complete response (CR)
- Low-grade NHL with intermediate 1 [int-1] per International Prognostic Scoring System [IPSS]) after > or = 1 prior cycle of induction chemotherapy; must have 3 mg/dL, or symptomatic biliary disease
- Human immunodeficiency virus (HIV) seropositive patients
- Patients with poorly controlled hypertension despite multiple antihypertensive medications
- Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding
- Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment
- Patients with active non-hematologic malignancies (except non-melanoma skin cancers) or those with non-hematologic malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within five years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy
- Active infectious disease concerns
- Karnofsky performance score < 60 Lansky performance score < 60
- Life expectancy severely limited by diseases other than malignancy
- Patients with a diagnosis of chronic myelomonocytic leukemia (CMML)
- Central nervous system (CNS) involvement with disease refractory to intrathecal chemotherapy
- Patients with AML, MDS, ALL, or CML must not have presence of circulating leukemic blasts detected by standard pathology
- Patients with aggressive lymphomas (such as DLBC) must not have bulky, rapidly progressive disease immediately prior to HCT
- Patients who have received a prior allogeneic HCT must have no active GVHD requiring immunosuppressive therapy for at least 21 days prior to start of conditioning
- DONOR: Children less than 12 years of age.
- DONOR: Children greater than or equal to 12 years of age who have not provided informed assent in the presence of a parent and an attending physician who is not a member of the recipient's care team
- DONOR: Children greater than or equal to 12 years of age who have inadequate peripheral vein access to safely undergo apheresis
- DONOR: Donors unable or unwilling to undergo marrow harvest for the initial HCT, storage of autologous blood prior to marrow harvest or apheresis one week after marrow harvest
- DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight [IBW]) for the initial HCT; the average nucleated cell content of harvested marrow is 22 x 10^6 nucleated cells/mL or 220 x 10^8 nucleated cells/Liter
- DONOR: HIV-positive donors
- DONOR: Donors who are cross-match positive with recipient
Data sourced from ClinicalTrials.gov (NCT00789776). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.