Donor Umbilical Cord Blood Transplant By Injection Into the Bone Marrow in Treating Patients With Hematologic Cancer

Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00295880
• Other study ID #: 2004LS072
• Secondary ID: UMN-MT2004-26UMN
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: February 23, 2006
• Last updated: December 3, 2017
• Start date: June 2005
• Est. completion date: August 2008

Study information

• Verified date: December 2017
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Lymphoma
• Myelodysplastic Syndromes
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Procedure:
• umbilical cord blood transplantation
The graft will be given by slow injection into each posterior iliac crest.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

References & Publications (1)

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 Tra — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median Number of Days to Neutrophil Engraftment	Number of days to neutrophil recovery observed in recipients of two umbilical cord blood units (UCB)administered i.v. Neutrophil recovery is defined as first of 3 consecutive days with ANC (absolute neutrophil count) greater than or equal to 500/ul.	Daily through Day 60 post transplant
Secondary	Number of Patients Achieving Neutrophil Recovery	Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months.	6 months
Secondary	Number of Patients With Evidence of Engraftment.	Number of patients who received both cord blood units and achieved sustained donor engraftment	1 year
Secondary	Number of Patients With Acute Graft-versus-host Disease (GVHD)	Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant.	100 days post transplant
Secondary	Number of Patients With Transplant-related Mortality (TRM)	Number of patients who were deceased at days 100 and 180 from any cause other than relapse.	Day 100 and Day 180
Secondary	Number of Patients Surviving at Day 100 and 1 Year.	Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant.	Day 100 and 1 year
Secondary	Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD)	Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant.	100 days post transplant
Secondary	Number of Patients With Chronic Graft-versus-host Disease (GVHD).	Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD.	1 year post transplant