Allogeneic Transplantation in Patients With Cutaneous T-Cell Lymphoma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00506129
• Collaborator: (none)
• Enrollment: 33
• Location: 1
• Arm: 1
• Duration (Months): 141
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to see if receiving a transplant of blood stem cells (cells that can produce blood) or bone marrow from either a related donor (brother, sister or other relative) or an unrelated voluntary donor will help patients with advanced cutaneous T-cell lymphoma. The length of time that patients who receive the treatment remain free of disease will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; Disorder Related to Bone Marrow Transplantation	Drug: Fludarabine; Drug: Melphalan; Procedure: Allogeneic Transplant; Drug: Thymoglobulin	Phase 2

Detailed Description

You will receive the chemotherapy drug fludarabine for 5 days (Days 1 to 5). The drug melphalan will be given on Days 4 and 5. You may also receive the drug anti-thymocyte globulin (ATG) on Days 4, 5, 6. This will be followed by infusion of blood stem cells or bone marrow from a donor on Day 7. A separate consent will be provided to the donor. The donor can be a brother, sister or another family member or a compatible unrelated donor. The drugs and the stem cells will be given through a catheter (a small tube) placed under the collarbone. You may receive your treatment on an inpatient or outpatient basis. If treated on an inpatient basis, you will stay in the hospital during treatment and recovery, which can take 4 to 5 weeks even if there are no complications.

The chemotherapy and the ATG are given to help the body accept the transplanted stem cells or bone marrow. You will receive antibiotics to fight infection and a medicine called G-CSF (Neupogen®) to help blood counts rise back to healthier levels. G-CSF is given as an injection under the skin. You will also need blood and platelet transfusions.

You will be given standard drugs to help decrease the risk of side effects. You may ask the study staff for information about how the drugs are given and their risks.

If the cancer grows and graft-versus-host disease is not present, you may be eligible to receive donor blood cells (lymphocytes) infused through the catheter. This may cause graft-versus-host disease and may help shrink the cancer. If the cancer grows and graft-versus-host disease is already present, then donor lymphocytes are not given.

Sometimes, the body rejects the donor cells; this reaction is called "graft rejection". Sometimes the donor cells attack the body, a reaction called graft-versus-host disease (GvHD). The drugs tacrolimus and methotrexate will be given to help prevent these reactions from occurring. These drugs are given through a vein or by mouth before and/or after the transplant.

You must stay in the Houston area for at least 100 days after the transplant. After 100 days, you must return to Houston every 3 months for 2 years for tests and checkups, then once a year for at least 3 years. If there is no sign of lymphoma growth at the follow up visit(s), you will receive no further treatment.

This is an investigational study. The drugs used in this study are approved by the FDA and are commercially available. As many as 35 patients will take part in the study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Study of Allogeneic Transplantation in Patients With Cutaneous T-Cell Lymphoma (CTCL)
• Study Start Date: Sep 1, 2003
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Jun 1, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Fludarabine + Melphalan with PBPC Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 Days prior to Allogeneic Transplant, Melphalan 70 mg/m^2 IV daily for 2 Days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.

Drug: Fludarabine; 25 mg/m^2 Given By Vein Daily for 5 Days Prior to Allogeneic Transplant.; Other Names: Fludarabine Phosphate Fludara ; Drug: Melphalan; 70 mg/m^2 Given By Vein Daily for 2 Days Prior to Allogeneic Transplant.; Procedure: Allogeneic Transplant; Allogeneic transplant given by vein after completion of Fludarabine and Melphalan.; Other Names: Allogeneic peripheral blood progenitor cell PBPC Bone Marrow transplantation Stem Cell Transplant SCT ; Drug: Thymoglobulin; 2 mg/kg/day by vein on days -3, -2 and -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.; Other Names: ATG Antithymocyte Globulin

Outcome Measures

Primary Outcome Measures

1. Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA) [Response assessed pre-transplant and 100 days post transplant with follow up at 1 year.]

   Response defined by Physician's Global Assessment of Clinical Condition (PGA) where Complete Response (CR) is No evidence of disease; 100% improvement; Partial Response (PR), one of following: 1) Very significant clearance ( > 90% to < 100%); only traces of disease remains; 2) Significant improvement ( > 75% to < 90%); some evidence of disease remain; 3) Intermediate between slight and marked improvement; ( > 50% to < 75%); 4) Some improvement ( > 25% to < 50%); however, significant evidence of disease remains; Stable Disease (SD): Disease has not changed from baseline condition (+<25%); Progressive Disease (PD): Disease is worse than at baseline evaluation by > 25% or more. Response confirmed by a second assessment at least 4 weeks following it. Assessments at baseline, pre and post transplant (100 days) then till disease progression or year one.

Secondary Outcome Measures

1. Average Overall Survival (OS) Length [Baseline to disease progression, followed up to 5 years post transplant]

   OS was defined as the time from transplantation to the date of death from any cause or last follow up, measured in days.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with pathologically proven cutaneous T-cell lymphoma (CTCL), disease stage IIB to IVB, patients must be in at least a partial response-PR (skin and lymph nodes) after receiving other non-allogeneic transplant therapy, age </= 70 years, Zubrod performance status 0 or 1, left ventricular ejection fraction >/= 50% or approved for transplant by a cardiologist, DLCO >/= 50% predicted or approved for transplant by a pulmonologist, serum creatinine </= 1.5 mg/dL, serum bilirubin < 2mg/dL. SGPT < 3 x upper limit of normal, and no previous history of allogeneic transplantation.

2. Donor: HLA-compatible related (HLA-A, -B, -DRB1 matched or with one-antigen mismatch) or HLA-compatible unrelated (HLA-A, -B, -C and -DRB1 matched or with one-antigen mismatch).

Exclusion Criteria:

1. Patients cannot have active central nervous system (CNS) disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center

Investigators

• Principal Investigator: Chitra M. Hosing, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00506129
• Other Study ID Numbers: DM03-0279; NCI-2012-01547
• First Posted: Jul 25, 2007
• Last Update Posted: Dec 29, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Cutaneous T-Cell Lymphoma; CTCL; Allogeneic Transplantation; Lymphoma; Allogeneic peripheral blood progenitor cell; PBPC; Bone Marrow transplantation; Stem Cell Transplant; SCT; Fludarabine; Fludarabine Phosphate; Fludara; Melphalan
• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Vidarabine; Fludarabine; Fludarabine phosphate; Melphalan; Thymoglobulin; Antilymphocyte Serum

Study Results

Participant Flow

Recruitment Details	Recruitment Period: September 26, 2003 to November 05, 2012. All recruitment done at The University of Texas MD Anderson Cancer Center.

Arm/Group Title	Fludarabine + Melphalan With PBPC
Arm/Group Description	Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
Period Title: Overall Study
STARTED	33
COMPLETED	11
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Fludarabine + Melphalan With PBPC
Arm/Group Description	Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
Overall Participants	33
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55
Sex: Female, Male (Count of Participants)
Female	18 54.5%
Male	15 45.5%
Region of Enrollment (participants) [Number]
United States	33 100%

Outcome Measures

1. Primary Outcome

Title	Participant's Response According to Physician's Global Assessment of Clinical Condition (PGA)
Description	Response defined by Physician's Global Assessment of Clinical Condition (PGA) where Complete Response (CR) is No evidence of disease; 100% improvement; Partial Response (PR), one of following: 1) Very significant clearance ( > 90% to < 100%); only traces of disease remains; 2) Significant improvement ( > 75% to < 90%); some evidence of disease remain; 3) Intermediate between slight and marked improvement; ( > 50% to < 75%); 4) Some improvement ( > 25% to < 50%); however, significant evidence of disease remains; Stable Disease (SD): Disease has not changed from baseline condition (+<25%); Progressive Disease (PD): Disease is worse than at baseline evaluation by > 25% or more. Response confirmed by a second assessment at least 4 weeks following it. Assessments at baseline, pre and post transplant (100 days) then till disease progression or year one.
Time Frame	Response assessed pre-transplant and 100 days post transplant with follow up at 1 year.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fludarabine + Melphalan With PBPC
Arm/Group Description	Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
Measure Participants	33
Complete Response (CR) Converted Post Transplant	19 57.6%
CR Prior to Transplant	6 18.2%
Partial Response (PR)	0 0%
Stable Disease (SD)	0 0%
Progressive Disease (PD)	16 48.5%

2. Secondary Outcome

Title	Average Overall Survival (OS) Length
Description	OS was defined as the time from transplantation to the date of death from any cause or last follow up, measured in days.
Time Frame	Baseline to disease progression, followed up to 5 years post transplant

Outcome Measure Data

Analysis Population Description

Baseline to disease progression, followed up to 5 years post transplant (assess at 100 days, every 3 months for 2 years, then once a year for at least 3 years)

Arm/Group Title	Fludarabine + Melphalan With PBPC
Arm/Group Description	Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
Measure Participants	33
Mean (Full Range) [Days]	1207

Adverse Events

Time Frame	Adverse events collected till 30 days following end of active treatment (the date of the stem cell infusion).
Arm/Group Title	Fludarabine + Melphalan With PBPC
Arm/Group Description	Fludarabine 25 mg/m^2 intravenous (IV) daily for 5 days prior to allogeneic peripheral blood progenitor cell (PBPC) , Melphalan 70 mg/m^2 IV daily for 2 days prior to IV Allogeneic Transplant following Fludarabine & Melphalan. Thymoglobulin 2 mg/kg/day IV on days -3, -2 & -1 for patients receiving matched unrelated marrow/stem cells or mismatched related marrow.
All Cause Mortality
	Fludarabine + Melphalan With PBPC
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Fludarabine + Melphalan With PBPC
	Affected / at Risk (%)	# Events
Total	0/33 (0%)
Other (Not Including Serious) Adverse Events
	Fludarabine + Melphalan With PBPC
	Affected / at Risk (%)	# Events
Total	33/33 (100%)
Blood and lymphatic system disorders
neutropenic fever	3/33 (9.1%)	3
Cardiac disorders
Primary graft failure with autologous reconstitution	1/33 (3%)	1
Cardiac Edema	6/33 (18.2%)	6
Cardiac Function	1/33 (3%)	1
Congestive heart failure	1/33 (3%)	1
Chest pain	1/33 (3%)	1
pericarditis	1/33 (3%)	1
tachycardia	2/33 (6.1%)	2
Gastrointestinal disorders
diarrhea	27/33 (81.8%)	27
mucositis	18/33 (54.5%)	18
flatulence	1/33 (3%)	1
nausea	32/33 (97%)	32
constipation	2/33 (6.1%)	2
dry mouth	1/33 (3%)	1
Upper gastrointestinal disorder, GvHD	1/33 (3%)	1
vomit	5/33 (15.2%)	5
constipation	1/33 (3%)	1
General disorders
fever	8/33 (24.2%)	8
fatigue	5/33 (15.2%)	5
fluid overload: Edema	10/33 (30.3%)	10
rigors	4/33 (12.1%)	4
pain	5/33 (15.2%)	5
abdomen pain	1/33 (3%)	1
pain	3/33 (9.1%)	4
Hepatobiliary disorders
transaminitis	29/33 (87.9%)	29
Infections and infestations
infection	17/33 (51.5%)	37
Injury, poisoning and procedural complications
Acute Graft versus Host Disease	1/33 (3%)	1
Investigations
increase T bilirubin	6/33 (18.2%)	6
Metabolism and nutrition disorders
anorexia	1/33 (3%)	1
hyperglycemia	5/33 (15.2%)	5
Musculoskeletal and connective tissue disorders
weakness, generalized	1/33 (3%)	1
muscular wasting	1/33 (3%)	2
myalgias	2/33 (6.1%)	2
bone pain	5/33 (15.2%)	5
Nervous system disorders
drowsiness	2/33 (6.1%)	2
dizziness	1/33 (3%)	1
headache	13/33 (39.4%)	13
Psychiatric disorders
anxiety	2/33 (6.1%)	2
Renal and urinary disorders
bladder	1/33 (3%)	1
renal failure	8/33 (24.2%)	8
frequency, urine	2/33 (6.1%)	2
hemorrhagic cystitis	3/33 (9.1%)	4
Acute Kidney Disease (renal disorder), dialysis	1/33 (3%)	1
dysuria	1/33 (3%)	1
Respiratory, thoracic and mediastinal disorders
pulmonary edema	1/33 (3%)	1
pleural effusion	2/33 (6.1%)	2
hiccoups	1/33 (3%)	1
pneumonitis	5/33 (15.2%)	5
shortness of breath	1/33 (3%)	1
Skin and subcutaneous tissue disorders
rash	7/33 (21.2%)	7
Vascular disorders
Hypertension	7/33 (21.2%)	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.