Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After MUD BMT

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00506922
• Collaborator: Astex Pharmaceuticals, Inc. (Industry)
• Enrollment: 150
• Location: 1
• Arms: 5
• Duration (Months): 110
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

Primary Objective:

1. To determine efficacy of escalating doses of pentostatin in combination with tacrolimus and methotrexate for the prevention of acute graft-versus-host disease (GVHD) in the context of unrelated donor and one antigen mismatched related donor transplantation.

Secondary Objectives:

1. To determine safety of escalating doses of pentostatin in combination with tacrolimus and methotrexate.

2. To reduce the incidence of acute GVHD following transplants with unrelated donor to 40%.

3. To document blood levels of tacrolimus when combined with pentostatin.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma	Drug: Pentostatin; Drug: Tacrolimus; Drug: Methotrexate	Phase 1/Phase 2

Detailed Description

During the study, patients will have blood, urine, bone marrow, and X-ray exams done. These exams are done to monitor the results of the transplantation. Blood tests will be done daily while patients are hospitalized.

Patients in this study will receive chemotherapy and/or radiation to treat their malignancy and prevent graft rejection. This is given before the infusion of donor cells.

Patients with myeloid leukemias may receive busulfan by vein (IV) for 4 days and cyclophosphamide by vein for 2 days.

Patients with lymphoid malignancies may receive thiotepa by vein in one dose, cyclophosphamide by vein for 2 days, and irradiation for 4 days.

Other chemotherapy treatments may be used before donor cell infusion.

IV injections will be given through a previously inserted catheter that extends into the vena cava (a large chest vein).

Patients will be randomly picked (as in the toss of a coin) to receive one of five different treatments. This is done to learn the benefit of pentostatin treatment and the appropriate dose. Four of the treatments will use different dose schedules of pentostatin. The fifth treatment group will receive no pentostatin at all. All patients receive tacrolimus and methotrexate.

Pentostatin will be given by vein in 4 doses during the first month after transplant. Tacrolimus (FK506) will be given by vein or mouth for 6 months. Methotrexate will be given by vein for 3 doses in the first week after transplant.

Patients will receive blood and platelet transfusions after the transplant. The number of transfusions will depend on how quickly the blood cell counts return to a normal range.

Patients will remain in the hospital for about 4-6 weeks and in the Houston area for 100 days after the transplant.

This is an investigational study. All of the study drugs are commercially available. Pentostatin will not be used for GVHD prevention outside of this study. A total of 150 patients will take part in this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Study of Pentostatin Combined With Tacrolimus and Mini-Methotrexate for GVHD Prevention After Matched-Unrelated Donor Blood and Marrow Transplantation
• Study Start Date: Sep 1, 2000
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: No Pentostatin Group 1: No Pentostatin	Drug: Pentostatin; Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2; Other Names: Nipent Deoxycoformycin DCF ; Drug: Tacrolimus; Given intravenously from day -2, and will be switched to oral dosing when tolerated.; Other Names: Prograf ; Drug: Methotrexate; Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 0.5 Group 2: Pentostatin 0.5 mg/m^2	Drug: Pentostatin; Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2; Other Names: Nipent Deoxycoformycin DCF ; Drug: Tacrolimus; Given intravenously from day -2, and will be switched to oral dosing when tolerated.; Other Names: Prograf ; Drug: Methotrexate; Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 1 Group 3: Pentostatin 1 mg/m^2	Drug: Pentostatin; Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2; Other Names: Nipent Deoxycoformycin DCF ; Drug: Tacrolimus; Given intravenously from day -2, and will be switched to oral dosing when tolerated.; Other Names: Prograf ; Drug: Methotrexate; Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 1.5 Group 4: Pentostatin 1.5 mg/m^2	Drug: Pentostatin; Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2; Other Names: Nipent Deoxycoformycin DCF ; Drug: Tacrolimus; Given intravenously from day -2, and will be switched to oral dosing when tolerated.; Other Names: Prograf ; Drug: Methotrexate; Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.
Experimental: Pentostatin 2 Group 5: Pentostatin 2 mg/m^2	Drug: Pentostatin; Given intravenously on days +8, +15, +22 and +30 post transplant: Group 2 - Pentostatin 0.5 mg/m^2 Group 3 - Pentostatin 1 mg/m^2 Group 4 - Pentostatin 1.5 mg/m^2 Group 5 - Pentostatin 2 mg/m^2; Other Names: Nipent Deoxycoformycin DCF ; Drug: Tacrolimus; Given intravenously from day -2, and will be switched to oral dosing when tolerated.; Other Names: Prograf ; Drug: Methotrexate; Given intravenously on days +1, +3, and +6 at the dose of 5 mg/m2.

Outcome Measures

Primary Outcome Measures

1. Number of Patients Without GVHD at 100 Days [100 days]

   The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients receiving allogeneic hematopoietic transplants from an unrelated donor or one antigen mismatched related donors.

2. Patients with AML, ALL, Hodgkin's disease, MDS (including CMML), CML in late chronic or accelerated phase or in blast crisis, and lymphoma in first or later relapses.

3. Patients must have bilirubin < 1.5 mg/dL, DLCO > 50% predicted, LVEF > 45% and performance status 0 or 1.

4. Candidates must have a creatinine level < 1.5 mg/dL or a calculated creatinine clearance > 60 ml/min.

Exclusion Criteria:

1. HIV seropositivity

2. Uncontrolled infection

3. Pregnancy

4. Candidates should not have received chemotherapy other than hydroxyurea or Gleevec for at least 3 weeks prior to treatment. Maintenance therapy with oral chemotherapy is acceptable. Treatment day is defined as transplant day +8, which is the date of first dose of pentostatin.

5. Diagnosis of myelofibrosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	U.T.M.D. Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Astex Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Marcos de Lima, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• UT MD Anderson Cancer Center website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00506922
• Other Study ID Numbers: ID00-132
• First Posted: Jul 25, 2007
• Last Update Posted: Apr 28, 2015
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Graft-Versus-Host Disease; GVHD Prevention; Hodgkin's Disease; Leukemia; Lymphoma; Methotrexate; Tacrolimus; Pentostatin
• Additional relevant MeSH terms: Leukemia; Methotrexate; Pentostatin; Tacrolimus

Study Results

Participant Flow

Recruitment Details	Recruitment Period: September 15, 2000 to July 26, 2007; All recruitment done at UT MD Anderson Cancer Center
Pre-assignment Detail	A total of 150 patients were enrolled, and 147 were available for analysis. Two patients assigned to the 1.5 mg/m^2 arm were removed without receiving treatment (due to ineligibility, and poor donor cell collection). A patient assigned to arm 2.0 mg/m^2 withdrew consent before being treated.

Arm/Group Title	No Pentostatin	Pentostatin 0.5	Pentostatin 1	Pentostatin 1.5	Pentostatin 2
Arm/Group Description	Group 1: No Pentostatin	Group 2: Pentostatin 0.5 mg/m^2	Group 3: Pentostatin 1 mg/m^2	Group 4: Pentostatin 1.5 mg/m^2	Group 5: Pentostatin 2 mg/m^2
Period Title: Overall Study
STARTED	37	10	29	63	11
COMPLETED	37	10	29	61	10
NOT COMPLETED	0	0	0	2	1

Baseline Characteristics

Arm/Group Title	No Pentostatin	Pentostatin 0.5	Pentostatin 1	Pentostatin 1.5	Pentostatin 2	Total
Arm/Group Description	Group 1: No Pentostatin	Group 2: Pentostatin 0.5 mg/m^2	Group 3: Pentostatin 1 mg/m^2	Group 4: Pentostatin 1.5 mg/m^2	Group 5: Pentostatin 2 mg/m^2	Total of all reporting groups
Overall Participants	37	10	29	63	11	150
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	36 97.3%	10 100%	28 96.6%	61 96.8%	11 100%	146 97.3%
>=65 years	1 2.7%	0 0%	1 3.4%	2 3.2%	0 0%	4 2.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50 (19)	42 (23)	47 (20)	50 (22)	45 (32)	46.8 (23.2)
Sex: Female, Male (Count of Participants)
Female	15 40.5%	3 30%	11 37.9%	30 47.6%	7 63.6%	66 44%
Male	22 59.5%	7 70%	18 62.1%	33 52.4%	4 36.4%	84 56%
Region of Enrollment (participants) [Number]
United States	37 100%	10 100%	29 100%	63 100%	11 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients Without GVHD at 100 Days
Description	The primary efficacy endpoint of escalating doses Pentostatin with Tacrolimus + Methotrexate is success, defined to be that the patient is alive, engrafted, and without acute graft-versus-host disease (GVHD) at 100 days.
Time Frame	100 days

Outcome Measure Data

Analysis Population Description

All analysis was intention to treat (ITT).

Arm/Group Title	Pentostatin
Arm/Group Description	150 patients were enrolled, 2 patients not treated, 38 patients were Group 1 (no Pentostatin), the remaining Groups 2,3,4 and 5, 110 patients were analysed that received the Pentostatin.
Measure Participants	147
Number [participants]	100 270.3%

Adverse Events

Time Frame	7 Years
Arm/Group Title	No Pentostatin		Pentostatin 0.5		Pentostatin 1		Pentostatin 1.5		Pentostatin 2
Arm/Group Description	Group 1: No Pentostatin		Group 2: Pentostatin 0.5 mg/m^2		Group 3: Pentostatin 1 mg/m^2		Group 4: Pentostatin 1.5 mg/m^2		Group 5: Pentostatin 2 mg/m^2
All Cause Mortality
	No Pentostatin		Pentostatin 0.5		Pentostatin 1		Pentostatin 1.5		Pentostatin 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	No Pentostatin		Pentostatin 0.5		Pentostatin 1		Pentostatin 1.5		Pentostatin 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/10 (0%)		0/29 (0%)		0/61 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	No Pentostatin		Pentostatin 0.5		Pentostatin 1		Pentostatin 1.5		Pentostatin 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	28/37 (75.7%)		9/10 (90%)		17/29 (58.6%)		40/61 (65.6%)		7/10 (70%)
Infections and infestations
CMV	21/37 (56.8%)	21	3/10 (30%)	3	12/29 (41.4%)	12	27/61 (44.3%)	27	5/10 (50%)	5
bacterial	24/37 (64.9%)	24	6/10 (60%)	6	17/29 (58.6%)	17	38/61 (62.3%)	38	7/10 (70%)	7
viral	5/37 (13.5%)	5	2/10 (20%)	2	7/29 (24.1%)	7	24/61 (39.3%)	24	1/10 (10%)	1
parasite	0/37 (0%)	0	0/10 (0%)	0	1/29 (3.4%)	1	3/61 (4.9%)	3	0/10 (0%)	0
fungal	5/37 (13.5%)	5	2/10 (20%)	2	7/29 (24.1%)	7	24/61 (39.3%)	24	1/10 (10%)	1
Renal and urinary disorders
Increased Creatinine	11/37 (29.7%)	11	6/10 (60%)	6	4/29 (13.8%)	4	21/61 (34.4%)	21	4/10 (40%)	4
TTP/HUS	0/37 (0%)	0	0/10 (0%)	0	0/29 (0%)	0	5/61 (8.2%)	5	7/10 (70%)	7

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.