Pentostatin and Lymphocyte Infusion in Preventing Graft Rejection in Patients Who Have Undergone Donor Stem Cell Transplant

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00096161
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 36
• Locations: 5
• Arm: 1
• Actual Duration (Months): 147
• Patients Per Site: 7.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This phase II trial studies pentostatin and donor lymphocyte infusion in preventing graft rejection in patients who have undergone donor stem cell transplant. Giving pentostatin and an infusion of the donor's T cells (donor lymphocyte infusion) after a donor stem cell transplant may stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells 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 pentostatin before donor lymphocyte infusion may stop this from happening.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Graft Versus Host Disease; Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Non-Hodgkin Lymphoma; Plasma Cell Myeloma; Waldenstrom Macroglobulinemia	Drug: Cyclosporine; Drug: Mycophenolate Mofetil; Drug: Pentostatin; Biological: Therapeutic Allogeneic Lymphocytes	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the safety and efficacy of the combined use of pentostatin and donor lymphocyte infusion (DLI) in patients with low or falling donor T-cell chimerism to prevent graft rejection after transplantation both from matched related donors (MRDs) or unrelated donors (URDs).

SECONDARY OBJECTIVES:

1. To determine the incidence of graft-versus-host disease (GvHD) infections and disease response, if persistent disease is present.

OUTLINE: This is a dose-escalation study of donor lymphocyte infusion.

GROUP I: Patients receive pentostatin intravenously (IV) over 20-30 minutes on day -2 and DLI over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same cluster of differentiation (CD)3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart.

GROUP II (initiated if patients in group I do not achieve sustained engraftment and improved chimerism): Patients receive treatment as in group I. Patients also receive cyclosporine orally (PO) twice daily (BID) on days -3 to 56 and mycophenolate mofetil PO once daily (QD) on days 0 to 27. Treatment continues in the absence of GvHD.

After completion of study treatment, patients are followed up every 6 months for 2 years and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pentostatin and Donor Lymphocyte Infusion for Low Donor T-cell Chimerism After Hematopoietic Cell Transplantation - A Multi-center Trial
• Actual Study Start Date: May 1, 2003
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: pentostatin, DLI, mycophenolate mofetil, cyclosporine Group I (pentostatin, DLI): Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Group II (pentostatin, DLI, mycophenolate mofetil, cyclosporine): Patients receive treatment as in group I. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD.

Drug: Cyclosporine; Given PO; Other Names: 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Neoral OL 27-400 Sandimmun Sandimmune SangCya ; Drug: Mycophenolate Mofetil; Given PO; Other Names: Cellcept MMF ; Drug: Pentostatin; Given IV; Other Names: (R)-3-(2-Deoxy-.beta.-D-erythro-pentofuranosyl)-3,6,7, 8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol 2'-Deoxycoformycin CI-825 Co-Vidarabine Covidarabine DCF Deoxycoformycin Nipent PD-81565 Pentostatine ; Biological: Therapeutic Allogeneic Lymphocytes; Given IV; Other Names: Allogeneic Lymphocytes

Outcome Measures

Primary Outcome Measures

1. Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism [From the time of enrollment maintained to day 56 after the last DLI, up to Day 112]

   A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then it can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements. "Chimerism" in hematopoietic cell transplant derives from this idea of a "mixed" entity, referring to someone who has received a transplant of genetically different tissue. A test for chimerism after a hematopoietic cell transplant involves identifying the genetic profiles of the recipient and of the donor and then evaluating the extent of mixture in the recipient's blood cells or marrow cells.

2. Incidence of Grade IV Acute GVHD [Within 100 days after the last DLI]

   Clinical Stage of acute GVHD according to Organ System Skin: - Maculopapular rash <25% of body surface - Maculopapular rash 25-50% of body surface - Maculopapular rash >50% body surface area or generalized erythroderma - Generalized erythroderma with bullous formation and desquamation Liver: - Bilirubin 2-3 mg/dl - Bilirubin 3.1-6 mg/dl - Bilirubin 6.1-15 mg/dl - Bilirubin >15 mg/dl Gut: - >500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD - >1000 -1500 mL diarrhea per day - >1500 mL diarrhea per day - >1500 mL diarrhea per day plus severe abdominal pain with or without ileus Overall Clinical Grading of Severity of acute GVHD Grade IV: 0-4 Skin, 2-4 Liver, and/or 2-4 GI

Secondary Outcome Measures

1. Incidence of GVHD [1 year after DLI]

   Percentage patients with acute or chronic GVHD. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.

2. Incidence of Infections [100 days after DLI]

3. Incidence of Relapse/Progression [1 year after DLI]

   CML Acquisition of a new cytogenetic abnormality and/or development of accelerated phase or blast crisis. Criteria for accelerated phase: unexplained fever >38.3° C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, BM blasts and promyelocytes >20%. AML, ALL, CMML >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL Progressive disease: ≥1 of: physical exam/imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ tx; or definite increase in the size/number of plasmacytomas or lytic bone lesions.

4. Survival [1 year after DLI]

   Percentage patients surviving.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patients having received a preceding allogeneic transplantation from either a human leukocyte antigen (HLA)-matched related or unrelated donor are eligible for this protocol

• Related donor: HLA genotypically identical at least at one haplotype and may be phenotypically or genotypically identical at the allele level at HLA A, B, C, DRB1, and DQB1

• Unrelated donor who are prospectively:

• Matched for HLA-A, B, C, DRB1 and DQB1 by high resolution typing; OR

• Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing

• Patients with less than 50% donor CD3 peripheral blood chimerism on two separate, consecutive evaluations; the two evaluations must be at least 14 days apart OR patients with absolute decreases of donor CD3 peripheral blood chimerism of >= 20% if the second test shows < 50% donor CD3 cells; the two evaluations must be at least 14 days apart

• Patients with evidence of disease are only eligible if the disease is stable (or persistent) in comparison to the status prior to transplantation

• Patients must be tapered off systemic steroids to a dosage of less than or equal to 0.25 mg/kg/day

• Patients must have persistent donor CD3 cells (>= 5% donor CD3 cells by a deoxyribonucleic acid [DNA]-based assay that compares the profile of amplified fragment length polymorphisms [ampFLP] [or fluorescent in situ hybridization (FISH) studies or variable number of tandem repeats (VNTR)])

• DONOR: Alternatively to a fresh unmodified leukapheresis product, previously collected cryopreserved peripheral blood stem cells (PBSC) after mobilization with G-CSF or cryopreserved unmodified leukapheresis product from the original donor can be used; if cryopreserved product is not available, the following criteria apply for the DLI product:

• DONOR: Original donor of hematopoietic cell transplantation

• DONOR: Donor must give consent to leukapheresis

• DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral or subclavian)

• DONOR: Donor must be medically fit to undergo the apheresis procedure (institutional guidelines for apheresis)

Exclusion Criteria:

• Current grade II to IV acute GVHD or extensive chronic GVHD

• Karnofsky score < 50%

• Pediatric criteria

• Lansky play-performance score < 40

• Evidence of relapse or progression of disease after transplantation

• Prior recipient of cord blood

• DONOR: Donors who are not suitable for medical reasons to donate peripheral blood mononuclear cells (PBMC) by continuous centrifugation according to the criteria of the American Association of Blood Banks (AABB)

• DONOR: Pregnancy

• DONOR: Human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection

• DONOR: Recent immunization may require a delay

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
2	LDS Hospital	Salt Lake City	Utah	United States	84143
3	VA Puget Sound Health Care System	Seattle	Washington	United States	98101
4	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
5	University of Torino	Torino		Italy	10126

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Brenda Sandmaier, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Brenda Sandmaier, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT00096161
• Other Study ID Numbers: 1825.00; NCI-2010-00230; 1825.00; P01CA078902; P30CA015704
• First Posted: Nov 9, 2004
• Last Update Posted: Jan 31, 2020
• Last Verified: Jan 1, 2020

• Additional relevant MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Waldenstrom Macroglobulinemia; Multiple Myeloma; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Graft vs Host Disease; Cyclosporine; Mycophenolic Acid; Vidarabine; Pentostatin; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Period Title: Overall Study
STARTED	20	10	6	0
COMPLETED	20	10	6	0
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)	Total
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Total of all reporting groups
Overall Participants	20	10	6	0	36
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 NaN	0 0%
Between 18 and 65 years	17 85%	7 70%	4 66.7%	0 NaN	28 77.8%
>=65 years	3 15%	3 30%	2 33.3%	0 NaN	8 22.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55	59.3	60.3	56.9
Sex: Female, Male (Count of Participants)
Female	2 10%	2 20%	1 16.7%	5 Infinity
Male	18 90%	8 80%	5 83.3%	31 Infinity
Region of Enrollment (participants) [Number]
United States	20 100%	10 100%	6 100%	36 Infinity

Outcome Measures

1. Primary Outcome

Title	Percentage Patients With an Increase of at Least 10 Percentage Points in Donor T-cell Chimerism
Description	A regimen will be considered successful if 20 patients are enrolled, at least 13 demonstrate improved chimerism. If fewer than 5 patients have shown improvement in chimerism then it can be at least 75% confident that the true rate of improvement is less than 0.53. Enrollment to the regimen will stop and the next regimen will be opened. Enrollment to a regimen may also be stopped at any time it becomes impossible to achieve 5 of 10 or 13 of 20 successful improvements. "Chimerism" in hematopoietic cell transplant derives from this idea of a "mixed" entity, referring to someone who has received a transplant of genetically different tissue. A test for chimerism after a hematopoietic cell transplant involves identifying the genetic profiles of the recipient and of the donor and then evaluating the extent of mixture in the recipient's blood cells or marrow cells.
Time Frame	From the time of enrollment maintained to day 56 after the last DLI, up to Day 112

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
Number [percentage of participants]	60 300%	30 300%	33.3 555%

2. Primary Outcome

Title	Incidence of Grade IV Acute GVHD
Description	Clinical Stage of acute GVHD according to Organ System Skin: - Maculopapular rash <25% of body surface - Maculopapular rash 25-50% of body surface - Maculopapular rash >50% body surface area or generalized erythroderma - Generalized erythroderma with bullous formation and desquamation Liver: - Bilirubin 2-3 mg/dl - Bilirubin 3.1-6 mg/dl - Bilirubin 6.1-15 mg/dl - Bilirubin >15 mg/dl Gut: - >500-1000 mL diarrhea per day or (nausea, anorexia or vomiting with biopsy (EGD) confirmation of upper GI GVHD - >1000 -1500 mL diarrhea per day - >1500 mL diarrhea per day - >1500 mL diarrhea per day plus severe abdominal pain with or without ileus Overall Clinical Grading of Severity of acute GVHD Grade IV: 0-4 Skin, 2-4 Liver, and/or 2-4 GI
Time Frame	Within 100 days after the last DLI

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
Number [percentage of participants]	5 25%	0 0%	0 0%

3. Secondary Outcome

Title	Incidence of GVHD
Description	Percentage patients with acute or chronic GVHD. The diagnosis of chronic GVHD requires at least one manifestation that is distinctive for chronic GVHD as opposed to acute GVHD. In all cases, infection and others causes must be ruled out in the differential diagnosis of chronic GVHD.
Time Frame	1 year after DLI

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
aGVHD	20 100%	0 0%	0 0%
cGVHD	50 250%	20 200%	16.7 278.3%

4. Secondary Outcome

Title	Incidence of Infections
Time Frame	100 days after DLI

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
Number [percentage of participants]	80 400%	70 700%	33.3 555%

5. Secondary Outcome

Title	Incidence of Relapse/Progression
Description	CML Acquisition of a new cytogenetic abnormality and/or development of accelerated phase or blast crisis. Criteria for accelerated phase: unexplained fever >38.3° C, new clonal cytogenetic abnormalities in addition to a single Ph-positive chromosome, BM blasts and promyelocytes >20%. AML, ALL, CMML >30% BM blasts w/ deteriorating performance status, or worsening of anemia, neutropenia, or thrombocytopenia. CLL Progressive disease: ≥1 of: physical exam/imaging studies (nodes, liver, and/or spleen) ≥50% increase or new, circulating lymphocytes by morphology and/or flow cytometry ≥50% increase, and lymph node biopsy w/ Richter's transformation. NHL >25% increase in the sum of the products of the perpendicular diameters of marker lesions, or the appearance of new lesions. MM ≥100% increase of the serum myeloma protein from its lowest level, or reappearance of myeloma peaks that had disappeared w/ tx; or definite increase in the size/number of plasmacytomas or lytic bone lesions.
Time Frame	1 year after DLI

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
Number [percentage of participants]	45 225%	20 200%	33.3 555%

6. Secondary Outcome

Title	Survival
Description	Percentage patients surviving.
Time Frame	1 year after DLI

Outcome Measure Data

Analysis Population Description

No subjects were enrolled onto Group 2D because the dose escalation was not triggered before the study closed to accrual.

Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)	Group 1B (Pentostatin, DLI Dose Level 2)	Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)	Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV	Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
Measure Participants	20	10	6	0
Number [percentage of participants]	60 300%	90 900%	66.7 1111.7%

Adverse Events

Time Frame	AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Adverse Event Reporting Description	One incident of GVHD was incorrectly reported as an SAE, as it is an expected complication of DLI. This patient outcome is recorded under deaths.
Arm/Group Title	Group 1A (Pentostatin, DLI Dose Level 1)		Group 1B (Pentostatin, DLI Dose Level 2)		Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)		Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
Arm/Group Description	Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (1x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV		Patients receive pentostatin IV over 20-30 minutes on day -2 and DLI (3x10^7 CD3+ cells/kg) over 15-30 minutes on day 0. Treatment may repeat once beginning with an escalated or same CD3-dose at least 4 weeks if persistent donor T-cells are documented, no GvHD has developed, and the chimerism status worsens or, if chimerism status is unchanged after at least 8 weeks with two subsequent tests of chimerism 4 weeks apart. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV		Patients receive treatment as in group 1A. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV		Patients receive treatment as in group 1B. Patients also receive cyclosporine PO BID on days -3 to 56 and mycophenolate mofetil PO QD on days 0 to 27. Treatment continues in the absence of GvHD. Pentostatin: Given IV Therapeutic Allogeneic Lymphocytes: Given IV
All Cause Mortality
	Group 1A (Pentostatin, DLI Dose Level 1)		Group 1B (Pentostatin, DLI Dose Level 2)		Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)		Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Group 1A (Pentostatin, DLI Dose Level 1)		Group 1B (Pentostatin, DLI Dose Level 2)		Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)		Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/20 (30%)		0/10 (0%)		0/6 (0%)		0/0 (NaN)
Blood and lymphatic system disorders
Anemia	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Hemolytic uremic syndrome	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Cardiac disorders
Atrial fibrillation	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Immune system disorders
GVHD	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Nervous system disorders
Peripheral motor neuropathy	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Other (Not Including Serious) Adverse Events
	Group 1A (Pentostatin, DLI Dose Level 1)		Group 1B (Pentostatin, DLI Dose Level 2)		Group 2C (Pentostatin, DLI Dose Level 1, Add'l IS)		Group 2D (Pentostatin, DLI Dose Level 2, Add'l IS)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/20 (50%)		2/10 (20%)		2/6 (33.3%)		0/0 (NaN)
Blood and lymphatic system disorders
Anemia	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Febrile neutropenia	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Hemolysis	1/20 (5%)	1	0/10 (0%)	0	1/6 (16.7%)	1	0/0 (NaN)	0
Thrombotic thrombocytopenic purpura	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Cardiac disorders
Cardiac troponin I increased	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Gastrointestinal disorders
Gastric hemorrhage	2/20 (10%)	3	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Ileal obstruction	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
General disorders
Fever	0/20 (0%)	0	1/10 (10%)	1	0/6 (0%)	0	0/0 (NaN)	0
Infections and infestations
Small intestine infection	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Investigations
Blood bilirubin increased	2/20 (10%)	2	0/10 (0%)	0	1/6 (16.7%)	1	0/0 (NaN)	0
Creatinine increased	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Forced expiratory volume decreased	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Investigations - Other, (Pancytopenia)	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Renal and urinary disorders
Acute kidney injury	1/20 (5%)	1	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	3/20 (15%)	3	1/10 (10%)	1	0/6 (0%)	0	0/0 (NaN)	0
Vascular disorders
Hypotension	2/20 (10%)	2	0/10 (0%)	0	0/6 (0%)	0	0/0 (NaN)	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.