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

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00295880
• Collaborator: (none)
• Enrollment: 12
• Arm: 1
• Duration (Months): 38

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes	Procedure: umbilical cord blood transplantation	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: Jun 1, 2005
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Transplant Patients Patients receiving umbilical cord blood transplantation.	Procedure: umbilical cord blood transplantation; The graft will be given by slow injection into each posterior iliac crest.; Other Names: UCBT

Outcome Measures

Primary Outcome Measures

1. Median Number of Days to Neutrophil Engraftment [Daily through Day 60 post transplant]

   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.

Secondary Outcome Measures

1. Number of Patients Achieving Neutrophil Recovery [6 months]

   Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months.

2. Number of Patients With Evidence of Engraftment. [1 year]

   Number of patients who received both cord blood units and achieved sustained donor engraftment

3. Number of Patients With Acute Graft-versus-host Disease (GVHD) [100 days post transplant]

   Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant.

4. Number of Patients With Transplant-related Mortality (TRM) [Day 100 and Day 180]

   Number of patients who were deceased at days 100 and 180 from any cause other than relapse.

5. Number of Patients Surviving at Day 100 and 1 Year. [Day 100 and 1 year]

   Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant.

6. Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD) [100 days post transplant]

   Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant.

7. Number of Patients With Chronic Graft-versus-host Disease (GVHD). [1 year post transplant]

   Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Study Chair: John E. Wagner, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00295880
• Other Study ID Numbers: 2004LS072; UMN-MT2004-26; UMN-0412M65789
• First Posted: Feb 24, 2006
• Last Update Posted: Dec 28, 2017
• Last Verified: Dec 1, 2017

• Keywords provided by Masonic Cancer Center, University of Minnesota: 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
• Additional relevant MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome

Study Results

Participant Flow

Recruitment Details	Patients are recruited from within the Department of Blood and Marrow Transplant Program. (Patients will be co-enrolled on study MT2005-10 (NCT00309842). Eligibility for this study are identical to MT2005-10.)

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Period Title: Overall Study
STARTED	12
COMPLETED	10
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (8)
Sex: Female, Male (Count of Participants)
Female	5 41.7%
Male	7 58.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Median Number of Days to Neutrophil Engraftment
Description	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.
Time Frame	Daily through Day 60 post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	10
Median (Full Range) [Days]	21

2. Secondary Outcome

Title	Number of Patients Achieving Neutrophil Recovery
Description	Number of patients with sustained neutrophil recovery with chimerism (evidence of engraftment of both cord blood transplants) at 6 months.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

Patients who completed treatment.

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	10
Number [Participants]	9 75%

3. Secondary Outcome

Title	Number of Patients With Evidence of Engraftment.
Description	Number of patients who received both cord blood units and achieved sustained donor engraftment
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

1 patient was not evaluable due to graft failure

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	10
Number [Participants]	2 16.7%

4. Secondary Outcome

Title	Number of Patients With Acute Graft-versus-host Disease (GVHD)
Description	Number of patients who exhibited grade II-IV acute GVHD at 100 days post umbilical cord blood transplant.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

2 patients were not graded for acute GVHD due to graft failure.

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	8
Number [Participants]	7 58.3%

5. Secondary Outcome

Title	Number of Patients With Transplant-related Mortality (TRM)
Description	Number of patients who were deceased at days 100 and 180 from any cause other than relapse.
Time Frame	Day 100 and Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	10
Number [Participants]	5 41.7%

6. Secondary Outcome

Title	Number of Patients Surviving at Day 100 and 1 Year.
Description	Overall survival of patients-Number of patients who were alive at Day 100 and 1 year post transplant.
Time Frame	Day 100 and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	10
Number [Participants]	5 41.7%

7. Secondary Outcome

Title	Number of Patients With Grade III-IV Acute Graft-versus-host Disease (GVHD)
Description	Number of umbilical cord blood transplant patients developing severe GVHD at 100 days post transplant.
Time Frame	100 days post transplant

Outcome Measure Data

Analysis Population Description

2 patients were not yet graded for acute gvhd

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	8
Number [Participants]	2 16.7%

8. Secondary Outcome

Title	Number of Patients With Chronic Graft-versus-host Disease (GVHD).
Description	Number of umbilical cord blood transplant patients with limited and extensive chronic GVHD.
Time Frame	1 year post transplant

Outcome Measure Data

Analysis Population Description

Only 7 patients were at risk for chronic GVHD

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
Measure Participants	7
Number [Participants]	2 16.7%

Adverse Events

Arm/Group Title	Umbilical Cord Blood Transplant Patients
Arm/Group Description	Patients with high-risk hematologic malignancy transplanted with umbilical cord blood via direct marrow injection.
All Cause Mortality
	Umbilical Cord Blood Transplant Patients
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Umbilical Cord Blood Transplant Patients
	Affected / at Risk (%)	# Events
Total	5/12 (41.7%)
Blood and lymphatic system disorders
graft failure	1/12 (8.3%)	1
Acute GVHD Grade 3	2/12 (16.7%)	2
General disorders
Death	5/12 (41.7%)	5
Other (Not Including Serious) Adverse Events
	Umbilical Cord Blood Transplant Patients
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

This study was terminated early based on interim statistical analysis that indicated time to engraftment will not be improved compared to historical controls. While safe, lack of faster marrow recovery supports early discontinuation.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.