Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00555048
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 1
• Locations: 2
• Arm: 1
• Patients Per Site: 0.5

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer 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. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the best dose of alemtuzumab when given together with busulfan and cyclophosphamide followed by a donor stem cell transplant and to see how well it works in treating patients with hematologic cancer.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases	Biological: alemtuzumab; Drug: busulfan; Drug: cyclophosphamide; Drug: methotrexate; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation	Phase 1/Phase 2

Detailed Description

OBJECTIVES:

Primary

• Identify the lowest dose of alemtuzumab that is associated with day 180 transplant-related mortality ≤ 45%.

Secondary

• Determine the incidence of life-threatening infection in patients receiving this treatment.

• Determine the incidence of grades III-IV acute graft-vs-host disease (GVHD) in patients receiving this treatment.

• Determine the survival at 1 year in patients receiving this treatment.

• Determine the incidence of disease relapse at 1 year in patients receiving this treatment.

• Determine the incidence of extensive chronic GVHD at 1 year in patients receiving this treatment.

• Determine the incidence of graft failure at day 100 in patients receiving this treatment.

OUTLINE:

• Chemotherapy: Patients receive alemtuzumab IV over 2 hours on days -10 to -6, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV on days -3 and -2.

• Peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic filgrastim (G-CSF)-mobilized PBSC transplantation on day 0.

• Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 50 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Primary Purpose: Treatment
• Official Title: A Prospective Trial to Evaluate the Role of In Vivo T Cell Depletion by Campath® (Alemtuzumab) in Reduction of Transplant Related Mortality in Transplantation From HLA-Class I or Class II Mismatched, Unrelated Donors
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Alemtuzumab Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.	Biological: alemtuzumab; Drug: busulfan; Drug: cyclophosphamide; Drug: methotrexate; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

Outcome Measures

Primary Outcome Measures

1. Lowest Dose of Alemtuzumab Associated With Transplant-related Mortality [Up to day 180]

   Lowest dose of alemtuzumab associated with transplant-related mortality at day 180

Secondary Outcome Measures

1. Life-threatening Infection [Up to 180 days]

2. Grades III-IV Acute Graft-vs-host Disease (GVHD) [Up to 100 days]

3. Overall Survival [Up to 1 year]

   Count of surviving participants at 1 year

4. Disease Relapse [Up to 1 year]

   Count of participants with disease relapse at 1 year

5. Extensive Chronic GVHD [Up to 1 year]

   Count of participants with extensive chronic GVHD at 1 year

6. Graft Failure [Up to day 100]

   Count of participants with graft failure at day 100

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Confirmed diagnosis of one of the following:

• Primary acute myeloid leukemia (AML) meeting any of the following criteria:

• First complete remission (CR; defined as < 5% blasts in marrow) with high-risk features as defined by failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following:

• -5/del(5q)

• -7/del(7q)

• Inversion 3q

• Abnormalities of 11q23, 20q, 21q, del(9q),

• Translocation 6;9

• Translocation 9;22

• Abnormalities of 17p

• Complex karyotype with ≥ 3 abnormalities

• Second CR or subsequent in remission

• Refractory or relapsed disease

• Secondary AML in remission or relapse

• Chronic myelogenous leukemia (CML) in accelerated or blast phase meeting the following criteria:

• Accelerated phase is defined by any one of the following:

• Blasts 10% to 19% of peripheral blood white cells or bone marrow cells

• Peripheral blood basophils ≥ 20%

• Persistent thrombocytopenia (< 100,000/mm³) unrelated to therapy, or persistent thrombocytosis (> 1,000,000/mm³) unresponsive to therapy

• Increasing spleen size and increasing WBC count unresponsive to therapy

• Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)

• Blast phase is defined by any of the following:

• Blasts ≥ 20% of peripheral blood white cells or bone marrow cells

• Extramedullary blast proliferation

• Large foci or clusters of blasts in bone marrow biopsy

• Primary myelodysplastic syndromes (MDS) with an IPSS score > 1.5

• Secondary MDS with any IPSS score

• Primary acute lymphoblastic leukemia meeting any of the following criteria:

• First CR (< 5% blasts in marrow) with high-risk features as defined by 1 of the following:

• Failure to achieve remission after first induction chemotherapy

• Presence of chromosomal abnormalities including hypodiploidy or abnormalities of 11q23 or translocation 9;22

• Second CR or subsequent in remission

• Refractory or relapsed disease

• No patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available

• No active CNS involvement with disease

• Donors must meet the following criteria:

• Unrelated volunteer donors who are mismatched for more than one HLA-class I alleles or antigens or for one HLA-class I antigen, but matched by high-resolution typing at HLA-DRB1 and -DQB1, OR who are mismatched for one or more HLA-class II alleles or antigens, but matched by high-resolution typing at HLA-A, -B, and -C

• No two-antigen mismatch at a single HLA-A, -B, or -C locus

• No mismatching of class I and class II HLA

• Matching must be based on results of high-resolution typing at HLA-A, -B, -C, - DRB1, and -DQB1

PATIENT CHARACTERISTICS:

• Karnofsky performance status 50-100%

• No symptomatic coronary artery disease or symptomatic congestive heart failure

• No hepatic disease with transaminases or bilirubin > 2 times upper limit of normal except for isolated hyperbilirubinemia attributed to Gilbert's syndrome

• No severe hypoxemia with room air P_AO_2 < 70, supplemental oxygen-dependence, or DLCO < 60% predicted

• No impaired renal function with creatinine > 2 times upper limit of normal or creatinine clearance < 50% normal

• Not HIV seropositive

• Not pregnant or breast-feeding

• Fertile patients must use effective contraception

• No active infections that are untreated or failing to respond to appropriate therapy

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

Exclusion criteria:

• Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation using a high-dose total-body irradiation regimen

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98104-1024
2	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ann E. Woolfrey, MD, Fred Hutchinson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00555048
• Other Study ID Numbers: 1981.00; P30CA015704; FHCRC-1981.00; CDR0000574145
• First Posted: Nov 7, 2007
• Last Update Posted: May 24, 2017
• Last Verified: Apr 1, 2017

• Keywords provided by Ann Woolfrey, Principal Investigator, Fred Hutchinson Cancer Center: graft versus host disease; adult acute megakaryoblastic leukemia (M7); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myelomonocytic leukemia (M4); adult acute promyelocytic leukemia (M3); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); childhood acute megakaryocytic leukemia (M7); childhood acute monoblastic leukemia (M5a); childhood acute monocytic leukemia (M5b); childhood acute myeloblastic leukemia with maturation (M2); childhood acute myeloblastic leukemia without maturation (M1); childhood acute myelomonocytic leukemia (M4); childhood acute promyelocytic leukemia (M3); accelerated phase chronic myelogenous leukemia; adult acute lymphoblastic leukemia in remission; adult acute myeloid leukemia in remission; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); blastic phase chronic myelogenous leukemia; childhood acute lymphoblastic leukemia in remission; childhood acute myeloid leukemia in remission; childhood chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia; recurrent childhood acute lymphoblastic leukemia; recurrent childhood acute myeloid leukemia; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; childhood myelodysplastic syndromes; de novo myelodysplastic syndromes; myelodysplastic/myeloproliferative diseases; secondary myelodysplastic syndromes
• Additional relevant MeSH terms: Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Syndrome; Cyclophosphamide; Busulfan; Methotrexate; Alemtuzumab; Tacrolimus

Study Results

Participant Flow

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Period Title: Overall Study
STARTED	1
COMPLETED	1
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Overall Participants	1
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	47
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	1 100%

Outcome Measures

1. Primary Outcome

Title	Lowest Dose of Alemtuzumab Associated With Transplant-related Mortality
Description	Lowest dose of alemtuzumab associated with transplant-related mortality at day 180
Time Frame	Up to day 180

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Number [mg total dose]	40

2. Secondary Outcome

Title	Life-threatening Infection
Time Frame	Up to 180 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Grades III-IV Acute Graft-vs-host Disease (GVHD)
Time Frame	Up to 100 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	0 0%

4. Secondary Outcome

Title	Overall Survival
Description	Count of surviving participants at 1 year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	1 100%

5. Secondary Outcome

Title	Disease Relapse
Description	Count of participants with disease relapse at 1 year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	0 0%

6. Secondary Outcome

Title	Extensive Chronic GVHD
Description	Count of participants with extensive chronic GVHD at 1 year
Time Frame	Up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	1 100%

7. Secondary Outcome

Title	Graft Failure
Description	Count of participants with graft failure at day 100
Time Frame	Up to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
Measure Participants	1
Count of Participants [Participants]	0 0%

Adverse Events

Arm/Group Title	Alemtuzumab
Arm/Group Description	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant. alemtuzumab busulfan cyclophosphamide methotrexate tacrolimus allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation
All Cause Mortality
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Alemtuzumab
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

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.