Donor Stem Cell Transplant in Treating Patients With Previously Treated Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

• Sponsor: Masonic Cancer Center, University of Minnesota (Other)
• Overall Status: Completed
• CT.gov ID: NCT00612716
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Actual Duration (Months): 242.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Giving chemotherapy, such as cyclophosphamide and busulfan, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells from bone marrow or umbilical cord blood may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving methotrexate and cyclosporine after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works in treating patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm	Drug: busulfan; Drug: cyclophosphamide; Biological: Stem cell infusion; Radiation: Total body irradiation	Phase 2

Detailed Description

OBJECTIVES:

• Determine if allogeneic stem cell transplantation using unrelated matched or related haploidentical donor bone marrow or unrelated matched cord blood results in timely, complete, and durable engraftment in patients with previously treated lymphoma, multiple myeloma, or chronic lymphocytic leukemia.

• Determine the incidence and grade of acute and chronic graft-versus-host disease in patients treated with this regimen.

• Determine if the augmented graft-versus-tumor effect accompanying unrelated or partially matched donor allogeneic transplant reduces the incidence of relapse in these patients.

OUTLINE:

• Preparative regimen: Patients receive cyclophosphamide IV over 2 hours on days -7 and -6 and undergo total-body irradiation (TBI) twice daily on days -4 to -1. Patients who are unable to undergo TBI receive busulfan IV or orally 4 times daily on days -9 to -6 and cyclophosphamide IV over 2 hours on days -5 to -2.

• Stem cell transplantation: All patients undergo unrelated matched bone marrow or umbilical cord blood transplantation or partially matched related allogeneic bone marrow transplantation on day 0.

• Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis comprising methotrexate and cyclosporine. Patients may be enrolled in other protocols directed towards GVHD prophylaxis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Unrelated or Partially Matched Allogeneic Donor Stem Cells for Lymphoma, Myeloma, and Chronic Lymphocytic Leukemia
• Actual Study Start Date: Oct 6, 1999
• Actual Primary Completion Date: Nov 15, 2019
• Actual Study Completion Date: Dec 15, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Allogeneic Transplantation Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.

Drug: busulfan; For those not eligible for total body irradiation: busulfan 4 mg/kg/day orally (1 mg/kg orally every 6 hrs) on Days -9 through -6.; Other Names: Busulfex ; Drug: cyclophosphamide; Cyclophosphamide 60 mg/kg/day on days -7 and -6. For patients not eligible for total body irradiation: cytoxan 50 mg/kg intravenously (IV) on days -5 through -2.; Other Names: Cytoxan ; Biological: Stem cell infusion; Infused on Day 0; Other Names: umbilical cord blood transplantation hematopoietic stem cell transplantation allogeneic transplantation bone marrow transplantation ; Radiation: Total body irradiation; 165 cGy morning and evening on days -4 through -1.; Other Names: TBI

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Engraftment Failure [3 Months]

   Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.

2. Number of Participants With Neutrophil Engraftment [Day 42]

   Time to 1st 3 consecutive days with absolute neutrophil count (ANC) > 5 x 10^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).

3. Number of Participants With Platelet Engraftment [Day 180]

   Time to platelets > 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment >50,000 by day 100.

4. Number of Participants With Grade 3-4 Acute Graft-versus-host Disease [Day 100]

   Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

5. Number of Participants With Persistence Disease [3 Years]

   the return of disease after its apparent recovery/cessation.

6. Number of Participants With Relapse of Malignancy [3 Years]

   the return of disease after its apparent recovery/cessation.

7. Number of Participants With 1 Year Overall Survival [1 year]

   The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.

8. Number of Participants With 2 Year Overall Survival [2 year]

   The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.

Secondary Outcome Measures

1. Number of Participants With of Chronic GVHD. [1 Year]

   Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Donors will be <55 years of age and in good health as approved by the National Marrow Donor Program (NMDP) donor and collection centers. Related donors will be < 70 years of age.

• Recipients will be <55 years, will have satisfactory organ function (excluding bone marrow) and will have a Karnofsky activity assessment >90% and will have:

• Creatinine <2.0 mg/dl.

• Bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <2 x normal.

• Pulmonary function test and Carbon Monoxide Diffusing Capacity (DLCO) > 50% of normal.

• Multi Gated Acquisition Scan (MUGA) >45% injection fraction.

• Recipients with unrelated donor matched at the HLA A, B, DRBI loci, or if < 35 years mismatched at a single HLA A or B, or DRBI locus.

• Umbilical cord blood (5) used as an unrelated stem cell source will provide > 2.0 x 10^7 cells/kg and will be matched at 4 - 6 of 6 HLA A, B, and DRBI loci. Cord blood grafts may include a single or pair of cord units depending on the cell dose.

• Partially matched related donors will be at least haploidentical (matched at >3 of 6 HLA A, B, DRB1 loci).

• Recipients will fall under one of the following disease categories

• Chronic lymphocytic leukemia -- must have all three:

• Rai Stage III/IV

• Progression after previous Complete Response (CR) or Partial Response (PR) including purine antagonist (i.e. fludarabine).

• Recent chemotherapy responsiveness

• Advanced non-Hodgkin's lymphoma(NHL).

• Low-grade NHL (Working Formulation A, B, C) following progression after initial therapy if asymptomatic at diagnosis (>CR2, >PR2; response duration < 1 year from last therapy) or if no CR was achieved (>PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).

• Mantle zone lymphoma after any progression following initial therapy (>CR1,

PR1). At least one prior therapy of intermediate intensity (e.g. CHOP).

• Intermediate grade lymphoma (>PR2). Response duration <1 year from prior therapy.

• High-grade Non-Hodgkin's Lymphoma (NHL) (IWF H, I, J) after initial therapy if >stage III at diagnosis; after any progression even if localized (stage I, II) at diagnosis with prior response duration < 1 year.

• Recent chemotherapy responsiveness after treatment with > 3 intermediate intensity regimens.

• Advanced Hodgkin's disease beyond PR2 (>CR3, >PR3).

• Recent chemotherapy responsiveness

• Multiple Myeloma (>CR2, >PR2) or after initial therapy if no prior PR.

• Recent chemotherapy responsiveness

• Recipients will sign informed consent approved by the Committee on the Use of Human Subjects at the University of Minnesota.

Exclusion Criteria:

• No available histocompatible related donor; 2nd bone marrow transplant (BMT), HIV-1 positive; active uncontrolled infection; or resistant malignancy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota	United States	55455

Sponsors and Collaborators

• Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Daniel J. Weisdorf, MD, Masonic Cancer Center, University of Minnesota

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 9, 2008

More Information

Publications

None provided.

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT00612716
• Other Study ID Numbers: 1999LS060; 9909M18181; UMN-MT1999-14
• First Posted: Feb 12, 2008
• Last Update Posted: Dec 9, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Masonic Cancer Center, University of Minnesota: stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; refractory multiple myeloma; recurrent adult Hodgkin lymphoma; recurrent/refractory childhood Hodgkin lymphoma; refractory chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; recurrent adult grade III lymphomatoid granulomatosis; adult nasal type extranodal NK/T-cell lymphoma; Waldenstrom macroglobulinemia; recurrent adult Burkitt lymphoma; stage I adult Burkitt lymphoma; stage II adult Burkitt lymphoma; stage III adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; stage I adult immunoblastic large cell lymphoma; stage II adult immunoblastic large cell lymphoma; stage III adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; stage I adult lymphoblastic lymphoma; stage II adult lymphoblastic lymphoma; stage III adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; recurrent marginal zone lymphoma; splenic marginal zone lymphoma; recurrent small lymphocytic lymphoma; recurrent childhood anaplastic large cell lymphoma; recurrent childhood grade III lymphomatoid granulomatosis; childhood diffuse large cell lymphoma; childhood immunoblastic large cell lymphoma; recurrent childhood large cell lymphoma; recurrent childhood lymphoblastic lymphoma; childhood nasal type extranodal NK/T-cell lymphoma; Burkitt lymphoma; recurrent childhood small noncleaved cell lymphoma; stage I childhood small noncleaved cell lymphoma; stage II childhood small noncleaved cell lymphoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood small noncleaved cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Plasmacytoma; Cyclophosphamide; Busulfan

Study Results

Participant Flow

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	1 16.7%
Unknown or Not Reported	5 83.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	1 16.7%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Engraftment Failure
Description	Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.
Time Frame	3 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	1 16.7%

2. Primary Outcome

Title	Number of Participants With Neutrophil Engraftment
Description	Time to 1st 3 consecutive days with absolute neutrophil count (ANC) > 5 x 10^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	5 83.3%

3. Primary Outcome

Title	Number of Participants With Platelet Engraftment
Description	Time to platelets > 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment >50,000 by day 100.
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	2 33.3%

4. Primary Outcome

Title	Number of Participants With Grade 3-4 Acute Graft-versus-host Disease
Description	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	3 50%

5. Primary Outcome

Title	Number of Participants With Persistence Disease
Description	the return of disease after its apparent recovery/cessation.
Time Frame	3 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	1 16.7%

6. Primary Outcome

Title	Number of Participants With Relapse of Malignancy
Description	the return of disease after its apparent recovery/cessation.
Time Frame	3 Years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	1 16.7%

7. Primary Outcome

Title	Number of Participants With 1 Year Overall Survival
Description	The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	2 33.3%

8. Primary Outcome

Title	Number of Participants With 2 Year Overall Survival
Description	The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date enrollment to date of death or censored at the date of last documented contact for patients still alive.
Time Frame	2 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	1 16.7%

9. Secondary Outcome

Title	Number of Participants With of Chronic GVHD.
Description	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Time Frame	1 Year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
Measure Participants	6
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	5 years
Arm/Group Title	Allogeneic Transplantation
Arm/Group Description	Patients receiving total body irradiation, stem cell infusion (allogeneic)transplantation using unrelated or partially matched allogeneic marrow or cord blood donors, busulfan, and cyclophosphamide.
All Cause Mortality
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Serious Adverse Events
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Injury, poisoning and procedural complications
Primary graft failure	1/6 (16.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Death	3/6 (50%)	3
Other (Not Including Serious) Adverse Events
	Allogeneic Transplantation
	Affected / at Risk (%)	# Events
Total	6/6 (100%)
Blood and lymphatic system disorders
Platelet refractory	1/6 (16.7%)	1
Anemia	1/6 (16.7%)	1
Disseminated Intravascular Coagulation	1/6 (16.7%)	1
Duodenal capillary congestion	1/6 (16.7%)	1
Hemolysis	4/6 (66.7%)	5
Subarachoid bleed	1/6 (16.7%)	1
Thrombosis	1/6 (16.7%)	2
Uremic platelet dysfunction	1/6 (16.7%)	2
Vascular disorder, other	1/6 (16.7%)	1
Veno occulisive disease	1/6 (16.7%)	1
Cardiac disorders
Cardiac disorder, other	1/6 (16.7%)	1
Pancytopenic	1/6 (16.7%)	1
Pericardial effusion	1/6 (16.7%)	1
Gastrointestinal disorders
GI bleeding	4/6 (66.7%)	5
Immune system disorders
Graft vs host disease	1/6 (16.7%)	1
Infections and infestations
Abnormal bilirubin	3/6 (50%)	6
Infection	5/6 (83.3%)	80
Pneumonia	3/6 (50%)	5
Sepsis	1/6 (16.7%)	1
Septicemia	1/6 (16.7%)	1
Investigations
Elevated Partial Thromboplastin Time	1/6 (16.7%)	1
Hypokalemic	1/6 (16.7%)	1
Hypomagnesmia	1/6 (16.7%)	1
Metabolism and nutrition disorders
Failure to thrive	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
muscle disorder other	1/6 (16.7%)	1
Myopathy	1/6 (16.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Active Malignancy	5/6 (83.3%)	6
Nervous system disorders
Epileptic episode	1/6 (16.7%)	1
Learning Dysfunction	1/6 (16.7%)	1
Neurotoxicity	2/6 (33.3%)	2
Seizure	1/6 (16.7%)	1
Renal and urinary disorders
Cyclosporine renal dysfunction	2/6 (33.3%)	2
Dialysis	3/6 (50%)	3
Embolization of uterine artery	1/6 (16.7%)	1
Hemolytic uremia	1/6 (16.7%)	1
Increased creatinine	2/6 (33.3%)	2
Renal failure	4/6 (66.7%)	4
Reproductive system and breast disorders
Acute sinusitis	1/6 (16.7%)	1
Hypogonadism	2/6 (33.3%)	2
Vaginal bleeding	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndorme	2/6 (33.3%)	2
Intubation	4/6 (66.7%)	4
Skin and subcutaneous tissue disorders
Drug toxicity	2/6 (33.3%)	2
Vascular disorders
Hypertension	4/6 (66.7%)	4

Limitations/Caveats

[Not Specified]

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.