Clinical trial NCT00295880: Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer
Official title: A Phase I/II Study of Double Unit Umbilical Cord Blood (UCB) Transplantation Utilizing Graft Administration Via Intra-Bone Marrow Injection (Companion Protocol to MT2000-25)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Myeloproliferative Disorders
Leukemia
Lymphoma
Myelodysplastic Syndromes
Keywords: adult acute myeloid leukemia in remission
adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory anemia with excess blasts
de novo myelodysplastic syndromes
myelodysplastic syndromes
adult diffuse large cell lymphoma
adult diffuse mixed cell lymphoma
adult diffuse small cleaved cell lymphoma
adult lymphoblastic lymphoma
grade 3 follicular lymphoma
mantle cell lymphoma
childhood large cell lymphoma
childhood lymphoblastic lymphoma
adult acute lymphoblastic leukemia
acute lymphoblastic leukemia
refractory anemia
refractory cytopenia
childhood acute myeloid leukemia
adult immunoblastic large cell lymphoma
blastic phase chronic myelogenous leukemia
chronic eosinophilic leukemia
chronic neutrophilic leukemia
childhood small noncleaved cell lymphoma
childhood myelodysplastic syndromes
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2006-02-24
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Rationale: Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from the donor's umbilical cord blood are injected into the patient's bone marrow they may help make stem cells, red blood cells, white blood cells, and platelets.

Purpose: This phase I/II trial is studying the side effects of donor umbilical cord blood transplant when given directly into the bone marrow and to see how well it works in treating patients with hematologic cancer.

Detailed description: Objectives:

Primary

* Determine the safety, in terms of infusional toxicity, of myeloablative unrelated donor double-unit umbilical cord blood (UCB) transplantation via intra-bone marrow injection (IBMI) in patients with advanced or high-risk hematologic malignancy.
* Determine whether treatment with this regimen improves the time to neutrophil engraftment (compared to historical controls) in these patients.

Secondary

* Determine the incidence of sustained donor engraftment in patients treated with this regimen.
* Determine the relative contribution of each UCB unit to initial and sustained donor engraftment in these patients.
* Determine the incidence of grade II-IV and grade III-IV acute graft-vs-host disease (GVHD) and chronic GVHD in patients treated with this regimen.
* Determine the incidence of day 100 and 180 transplant-related mortality in patients treated with this regimen.
* Determine the probability of survival at 100 days and 1 year post-transplantation in these patients.

Outline: This is a nonrandomized study.

Patients receive a myeloablative conditioning regimen. Patients also receive immunosuppression, growth factor, and supportive care as in protocol MT2005-10 (NCT00309842).

Patients receive 2 units of donor umbilical cord blood (UCB) by intra-bone marrow injection (IBMI) over 10 minutes each on day 0. If the IBMI procedure is not possible, then the UCB units are given intravenously (IV.)

After completion of study therapy, patients are followed periodically for 5 years.

Projected Accrual: A total of 36 patients will be accrued for this study.

Eligibility criteria: Inclusion Criteria:

* Acute myeloid leukemia (AML): high risk CR1
* Acute lymphocytic leukemia (ALL): high risk CR1 \[t(9;22), t (1:19), t(4;11) or other MLL rearrangements\] or \> 1 cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
* Chronic myelogenous leukemia (CML) excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate.
* Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics.
* Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm).
* Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+.
* Large cell NHL \> CR2/\> PR2. Patients in CR2/PR2 with initial short remission (\<6 months) are eligible.
* Lymphoblastic lymphoma.
* Multiple myeloma beyond PR2.
* Karnofsky performance status (PS) 90-100% (adults)
* Lansky PS 50-100% (children)
* Acceptable organ function

Exclusion Criteria:

* Active infection at time of transplantation
* History of HIV infection
* Pregnant or breast feeding.
* Chemotherapy refractory large cell and high grade NHL (ie progressive disease after \> 2 salvage regimens)
* Extensive prior therapy including \> 12 months alkylator therapy or \> 6 months alkylator therapy with extensive radiation.
* Diffuse myelofibrosis of BM (bone marrow) (any severity) regardless of primary diagnosis (focal fibrosis acceptable provided it involves \< 20% of BM volume).
* History of pelvic irradiation.

Primary outcomes:
measure: Median Number of Days to Neutrophil Engraftment
timeFrame: Daily through Day 60 post transplant
Secondary outcomes:
measure: Number of Patients Achieving Neutrophil Recovery
timeFrame: 6 months
measure: Number of Patients With Evidence of Engraftment.
timeFrame: 1 year
measure: Number of Patients With Acute Graft-versus-host Disease (GVHD)
timeFrame: 100 days post transplant
measure: Number of Patients With Transplant-related Mortality (TRM)
timeFrame: Day 100 and Day 180
measure: Number of Patients Surviving at Day 100 and 1 Year.
timeFrame: Day 100 and 1 year
measure: Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD)
timeFrame: 100 days post transplant
measure: Number of Patients With Chronic Graft-versus-host Disease (GVHD).
timeFrame: 1 year post transplant
Other outcomes:
Locations:
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: John E. Wagner, MD
role: STUDY_CHAIR
References:
citation: Brunstein CG, Barker JN, Weisdorf DJ, Defor TE, McKenna D, Chong SY, Miller JS, McGlave PB, Wagner JE. Intra-BM injection to enhance engraftment after myeloablative umbilical cord blood transplantation with two partially HLA-matched units. Bone Marrow Transplant. 2009 Jun;43(12):935-40. doi: 10.1038/bmt.2008.417. Epub 2009 Jan 12.